Medicinal plants of China and its neighborhood: bioresources for tomorrow's drugs and cosmetics 9781439899120, 1820255611, 1439899126, 9781439899113, 1439899118

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Medicinal Plants of China, Korea, and Japan Bioresources for Tomorrow’s Drugs and Cosmetics Christophe Wiart, PharmD, PhD

Medicinal Plants of China, Korea, and Japan Bioresources for Tomorrow’s Drugs and Cosmetics

Medicinal Plants of China, Korea, and Japan Bioresources for Tomorrow’s Drugs and Cosmetics Christophe Wiart, PharmD, PhD School of Biomedical Science The University of Nottingham

Boca Raton London New York

CRC Press is an imprint of the Taylor & Francis Group, an informa business

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2012 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20120409 International Standard Book Number-13: 978-1-4398-9912-0 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http:// www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

Contents Chemical Structures�������������������������������������������������������������������������������������������������������������������������ix Foreword���������������������������������������������������������������������������������������������������������������������������������������� xiii Preface��������������������������������������������������������������������������������������������������������������������������������������������� xv Author��������������������������������������������������������������������������������������������������������������������������������������������xvii Chapter 1 Superorder Austrobaileyanae (Croizat) Doweld ex M.W. Chase & Reveal, 2009........ 1 1.1

Order Austrobaileyales Takht. ex Reveal, 1992.................................................1 1.1.1 Family Schisandraceae Blume, 1830, nom. cons., the Schisandra Family...................................................................................................1 1.1.1.1 Kadsura scandens Bl.............................................................1 1.1.1.2 Schisandra chinensis (Turcz.) Baill.......................................3 References..................................................................................................................... 4 Chapter 2 Superorder Magnolianae Takht., 1967.......................................................................... 7 2.1

Order Piperales Bercht. & J. Presl, 1820............................................................ 8 2.1.1 Family Saururaceae F. Voigt in L.C.M. Richard, 1811, nom. cons., the Lizard’s-Tail Family........................................................................ 8 2.1.1.1 Houttuynia cordata Thunb.................................................... 8 2.1.1.2 Saururus chinensis (Lour.) Baill......................................... 10 2.2 Order Laurales Juss. ex Bercht. & J. Presl, 1820.............................................. 12 2.2.1 Family Calycanthaceae Lindl., 1819, nom. cons., the Strawberry Shrub Family....................................................................................... 12 2.2.1.1 Chimonanthus praecox (L.) Link........................................ 13 2.2.2 Family Hernandiaceae Blume, 1826, nom. cons., the Hernandia Family................................................................................................. 15 2.2.2.1 Illigera appendiculata Bl. ................................................... 15 2.2.2.2 Illigera luzoniensis (Presl) Merr. ........................................ 17 References................................................................................................................... 18 Chapter 3 Superorder Lilianae Takht., 1967................................................................................ 23 3.1

Commelinids.................................................................................................... 23 3.1.1 Order Commelinales Mirb. ex Bercht. & J. Presl, 1820......................24 3.1.1.1 Family Pontederiaceae Kunth, 1816, nom. cons., the Water-Hyacinth Family..................................................24 3.1.2 Order Zingiberales Griseb., 1854........................................................ 29 3.1.2.1 Family Cannaceae Juss., 1789, nom. cons., the Canna Family.................................................................................. 29 3.1.2.2 Family Zingiberaceae Martinov, 1820, nom. cons., the Ginger Family................................................................ 30 3.1.3 Order Poales Small, 1903.................................................................... 73 3.1.3.1 Family Cyperaceae Juss., 1789, nom. cons., the Sedge Family.................................................................................. 73

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3.2

Non-Commelinids............................................................................................ 86 3.2.1 Order Asparagales Link, 1829............................................................ 88 3.2.1.1 Family Orchidaceae Juss., 1789, nom. cons., the Orchid Family................................................................ 88 3.2.2 Order Liliales Perleb, 1826................................................................ 131 3.2.2.1 Family Liliaceae Juss., 1789, nom. cons., the Lily Family.................................................................. 131 3.2.3 Order Alismatales R.Br. ex Bercht. & J. Presl, 1820........................ 165 3.2.3.1 Family Alismataceae Vent., 1799, nom. cons., the Water-Plantain Family................................................. 165 3.2.3.2 Family Hydrocharitaceae Juss., 1789, nom. cons., the Tape-Grass Family...................................................... 167 References................................................................................................................. 169 Chapter 4 Superorder Ranunculanae Takht. ex Reveal, 1992................................................... 191 4.1

Order Ranunculales Juss. ex Bercht. & J. Presl, 1820.................................... 191 4.1.1 Family Ranunculaceae Juss., 1789, nom. cons., the Buttercup Family......................................................................... 192 4.1.1.1 Aconitum fischeri Rchb..................................................... 193 4.1.1.2 Anemone chinensis Bunge................................................. 195 4.1.1.3 Cimicifuga foetida L. ........................................................ 196 4.1.1.4 Clematis chinensis Osbeck................................................ 198 4.1.1.5 Clematis gouriana Roxb. ex DC....................................... 199 4.1.1.6 Coptis chinensis Franch. .................................................. 201 4.1.1.7 Paeonia lactiflora Pall.......................................................202 4.1.1.8 Paeonia suffruticosa Andrews..........................................204 4.1.1.9 Ranunculus sceleratus L...................................................206 4.1.1.10 Semiaquilegia adoxoides (DC.) Makino...........................207 4.1.2 Family Lardizabalaceae R.Br., 1821, nom. cons., the Lardizabala Family......................................................................209 4.1.2.1 Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson.......209 References................................................................................................................. 210 Chapter 5 Superorder Rosanae Takht., 1967.............................................................................. 215 5.1

Eurosids I........................................................................................................ 215 5.1.1 Order Celastrales Link, 1829............................................................ 218 5.1.1.1 Family Celastraceae R.Br. in M. Flinders, 1814, nom. cons., the Bittersweet Family.................................... 218 5.1.2 Order Fagales Engl., 1892.................................................................224 5.1.2.1 Family Myricaceae Rich. ex Kunth, 1817, nom. cons., the Bayberry Family..........................................................224 5.2 Eurosids II...................................................................................................... 227 5.2.1 Order Myrtales Juss. ex Bercht. & J. Presl, 1820.............................. 230 5.2.1.1 Family Lythraceae J. St.-Hil., 1805, nom. cons., the Loosestrife Family....................................................... 230 5.2.2 Order Brassicales Bromhead, 1838................................................... 233 5.2.2.1 Family Brassicaceae Burnett, 1835, nom. cons., the Mustard Family............................................................ 233 References................................................................................................................. 247

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Chapter 6 Superorder Saxifraganae Reveal, 1994..................................................................... 255 6.1

Order Saxifragales Bercht. & J. Presl, 1820................................................... 255 6.1.1 Family Haloragaceae R.Br. (in M. Flinders, 1814), nom. cons., the Water Milfoil Family................................................................... 255 6.1.1.1 Myriophyllum spicatum L................................................. 256 References................................................................................................................. 258 Chapter 7 Superorder Santalanae Thorne ex Reveal, 1992....................................................... 259 7.1

Order Santalales R.Br. ex Bercht. & J. Presl, 1820........................................ 259 7.1.1 Family Loranthaceae Juss., 1808, nom. cons., the Showy Mistletoe Family............................................................................... 259 7.1.1.1 Dendrophthoe pentandra (L.) Miq. .................................. 261 7.1.1.2 Macrosolen cochinchinensis (Lour.) Tiegh....................... 262 7.1.1.3 Macrosolen robinsonii (Gamble) Danser.......................... 263 7.1.1.4 Macrosolen tricolor (Lecomte) Danser.............................264 7.1.1.5 Scurrula ferruginea (Jack) Danser.................................... 265 7.1.1.6 Scurrula parasitica L........................................................266 7.1.1.7 Taxillus kaempferi (DC.) Danser....................................... 268 7.1.1.8 Viscum articulatum Burm.f............................................... 269 7.1.1.9 Viscum ovalifolium DC. .................................................... 271 References................................................................................................................. 272 Chapter 8 Superorder Caryophyllanae Takht., 1967.................................................................. 275 8.1

Order Caryophyllales Juss. ex Bercht. & J. Presl, 1820................................. 275 8.1.1 Family Caryophyllaceae Juss., 1789, nom. cons., the Pink Family................................................................................. 276 8.1.1.1 Arenaria serpyllifolia L. ................................................... 277 8.1.1.2 Dianthus chinensis L. ....................................................... 278 8.1.1.3 Drymaria cordata (L.) Willd., Roem., & Schult...............280 8.1.1.4 Gypsophila oldhamiana Miq. ........................................... 281 8.1.1.5 Lychnis coronata Thunb. .................................................. 282 8.1.1.6 Pseudostellaria heterophylla (Miq.) Pax...........................284 8.1.1.7 Sagina saginoides (L.) H. Karst........................................ 285 8.1.1.8 Saponaria vaccaria L. ...................................................... 286 8.1.1.9 Silene aprica Turcz. .......................................................... 287 8.1.1.10 Stellaria media (L.) Vill.................................................... 289 8.1.1.11 Stellaria saxatilis Buch.-Ham. ex D. Don......................... 290 8.1.2 Family Droseraceae Salisb., 1808, nom. cons., the Sundew Family............................................................................................... 291 8.1.2.1 Drosera rotundifolia L...................................................... 292 References................................................................................................................. 293 Chapter 9 Superorder Asteranae Takht., 1967........................................................................... 297 9.1

Order Ericales Bercht. & J. Presl, 1820.......................................................... 297 9.1.1 Family Primulaceae Batsch ex. Borkh., 1797, nom. cons., the Primrose Family.......................................................................... 298 9.1.1.1 Androsace umbellata (Lour.) Merr. .................................. 299 9.1.1.2 Lysimachia foenum-graecum Hance................................. 301

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9.1.1.3 Lysimachia japonica Thunb..............................................302 9.1.1.4 Lysimachia liui S.S. Chien................................................ 303 9.1.1.5 Lysimachia paridiformis Franch.......................................304 9.1.1.6 Lysimachia phyllocephala Hand.-Mazz............................ 305 9.1.1.7 Primula sieboldii E. Morren.............................................306 9.2 Euasterids I.....................................................................................................307 9.2.1 Order Garryales Mart., 1835............................................................. 310 9.2.1.1 Family Eucommiaceae Engl., 1907, nom. cons., the Eucommia Family....................................................... 310 9.2.2 Order Gentianales Juss. ex Bercht. & J. Presl, 1820......................... 312 9.2.2.1 Family Gentianaceae Juss., 1789, nom. cons., the Gentian Family............................................................ 312 9.2.3 Order Lamiales Bromhead, 1838...................................................... 327 9.2.3.1 Family Oleaceae Hoffmanns. & Link, 1809, nom. cons., the Olive Family...................................................... 327 9.2.3.2 Family Orobanchaceae Vent., 1799, nom. cons., the Broom-Rape Family.................................................... 341 9.2.3.3 Family Plantaginaceae Juss. 1789, nom. cons., the Plantain Family............................................................344 9.2.4 Order Solanales Juss. ex Bercht. & J. Presl, 1820.............................346 9.2.4.1 Family Hydrophyllaceae R.Br. 1817, nom. cons., the Waterleaf Family.........................................................346 9.3 Euasterids II....................................................................................................348 9.3.1 Order Asterales Link, 1829............................................................... 350 9.3.1.1 Family Campanulaceae Juss., 1789, nom. cons., the Bellflower Family........................................................ 350 9.3.2 Order Apiales Nakai, 1930................................................................ 354 9.3.2.1 Family Apiaceae Lindl., 1836, nom. cons., the Carrot Family................................................................................ 354 9.3.3 Order Dipsacales Juss. ex Bercht. & J. Presl., 1820.......................... 376 9.3.3.1 Family Dipsacaceae Juss., 1789, nom. cons., the Teasel Family............................................................... 376 References................................................................................................................. 378

Chemical Structures Abiraterone�������������������������������������������������������������������� 288 Acetaminophen�������������������������������������������������������� 34, 232 Acetoxychavicol acetate�������������������������������������������������� 36 Acetylcholine����������������������������������������������������������������� 376 Aconitine������������������������������������������������������������������������ 195 Actinodaphnine���������������������������������������������������������������� 18 Aeginetolide������������������������������������������������������������������� 342 Aldosterone�������������������������������������������������������������������� 166 Alismol��������������������������������������������������������������������������� 165 Alisol B monoacetate����������������������������������������������������� 166 Alpinolide������������������������������������������������������������������������ 40 Amplizone������������������������������������������������������������������������ 27 Anemonin����������������������������������������������������������������������� 192 Anethol��������������������������������������������������������������������������� 355 Apigenin������������������������������������������������������������������������� 290 Artemisinin���������������������������������������������������������������������� 40 Astragaloside IV������������������������������������������������������������ 197 Aucubin������������������������������������������������������������������ 312, 345 AZT���������������������������������������������������������������������������������� 10 Benzyl benzoate��������������������������������������������������������������� 63 Benzylisothiocyanate����������������������������������������������������� 243 Berberine������������������������������������������������������������������������ 202 Beta-amyrin�������������������������������������������������������������������� 272 Beta-elemene�������������������������������������������������������������������� 50 Beta-1,2,3-tri-O-galloyl-4,6-(S)hexahydroxydiphenoyl-d-glucose���������������������������������� 257 Betulinic acid����������������������������������������������������������������� 195 Bicuculline��������������������������������������������������������������������� 329 Bornyl acetate������������������������������������������������������������������ 45 Bulbophythrin A��������������������������������������������������������������� 89 Busulfan������������������������������������������������������������������������� 236 Butylidene phthalide������������������������������������������������������ 356 Byakangelicin���������������������������������������������������������������� 365 Byakangelicol���������������������������������������������������������������� 359 Calanquinone A���������������������������������������������������������������� 97 Calycanthidine����������������������������������������������������������������� 13 Calycanthine�������������������������������������������������������������������� 13 Camptothecin����������������������������������������������������������������� 241 Cardamomin��������������������������������������������������������������������� 34 Carvacrol������������������������������������������������������������������������ 376 Catalpol�������������������������������������������������������������������������� 345 3-S-(+)-Catechol������������������������������������������������������������ 257 Chapecoderin C�������������������������������������������������������������� 165 Chavicol acetate��������������������������������������������������������������� 34 Cineole����������������������������������������������������������������������������� 31 Cis-hinokiresinol���������������������������������������������������� 135, 232 Coelonin������������������������������������������������������������������������� 109 Colchicine���������������������������������������������������������������������� 132 Coniine��������������������������������������������������������������������������� 354 Coriolic acid��������������������������������������������������������������������� 16

Cortisone acetate������������������������������������������������������������ 283 Costunolide���������������������������������������������������������������������� 48 Cuneataside B���������������������������������������������������������������� 210 Curculigoside����������������������������������������������������������������� 139 Curcumenol���������������������������������������������������������������������� 52 Curcumin�������������������������������������������������������������������������� 31 Curdione��������������������������������������������������������������������������� 51 Cymbinodin A���������������������������������������������������������������� 100 Cyperaquinones���������������������������������������������������������������� 74 Decursin������������������������������������������������������������������������� 361 Dehydrocurdione�������������������������������������������������������������� 52 Delphinine���������������������������������������������������������������������� 192 Demethoxycurcumin�������������������������������������������������������� 51 Denbinobin��������������������������������������������������������������������� 102 Dendrobine��������������������������������������������������������������������� 106 Densiflorol B�������������������������������������������������������������������� 89 3-Deoxyaulacocarpin A��������������������������������������������������� 39 Dianthin B���������������������������������������������������������������������� 279 Dihydropyranone����������������������������������������������������������� 260 2-(1,4-Dihydroxycyclohexanyl)-acetic acid������������������ 329 3,4-Dimethoxycinnamyl alcohol������������������������������������ 206 Diosgenin����������������������������������������������������������������������� 132 Doxorubicin������������������������������������������������������������������� 147 Droserone����������������������������������������������������������������������� 291 Elaeochytrin A��������������������������������������������������������������� 354 Embelin�������������������������������������������������������������������������� 299 E-phytol�������������������������������������������������������������������������� 142 Eremanthin����������������������������������������������������������������������� 48 Ergosterol peroxide�������������������������������������������������������� 288 Erianin������������������������������������������������������������������������������ 89 Erianthridin�������������������������������������������������������������������� 106 Erythrodiol��������������������������������������������������������������������� 327 Esculetin������������������������������������������������������������������������� 331 Etoposide�������������������������������������������������������������������������� 15 Falcaindiol���������������������������������������������������������������������� 370 Falcarindiol�������������������������������������������������������������������� 357 Falcarinol����������������������������������������������������������������������� 357 Ferulic acid��������������������������������������������������������������������� 363 Ficusal���������������������������������������������������������������������������� 342 Foenumoside������������������������������������������������������������������ 302 Folicanthine���������������������������������������������������������������������� 14 Forsythialan A���������������������������������������������������������������� 329 Forsythiaside������������������������������������������������������������������ 328 Fluoroquinolone��������������������������������������������������������������� 26 Furanodiene���������������������������������������������������������������������� 52 Galanal A������������������������������������������������������������������������� 67 Galangin��������������������������������������������������������������������������� 43 Galanthamine����������������������������������������������������������������� 132 Gamma amino butyric acid������������������������������������ 238, 359 Geniposidic acid������������������������������������������������������������� 312

ix

x Gentiakochianin������������������������������������������������������������� 322 Gentianine���������������������������������������������������������������������� 319 Gentiopicroside�������������������������������������������������������������� 313 Gentiside A��������������������������������������������������������������������� 321 Germacrone���������������������������������������������������������������������� 53 Gigantol�������������������������������������������������������������������������� 100 [6]-Gingerol��������������������������������������������������������������������� 66 Gingerols�������������������������������������������������������������������������� 31 Gomisin A�������������������������������������������������������������������������� 4 Goodyerin���������������������������������������������������������������������� 111 Goodyeroside A������������������������������������������������������������� 111 Grevillol������������������������������������������������������������������������� 302 Habenariol���������������������������������������������������������������������� 114 Hanalpinol������������������������������������������������������������������������ 40 Hanamyol������������������������������������������������������������������������� 40 Hedychenone�������������������������������������������������������������������� 62 Hedychilactone A������������������������������������������������������������� 58 Hedychilactone B������������������������������������������������������������� 58 Hesperidin���������������������������������������������������������������������� 336 Homoisoflavone������������������������������������������������������������� 157 Homoisoflavanone������������������������������������������������������������ 99 Hydrastine���������������������������������������������������������������������� 193 9-Hydroxy-4-methoxypsoralen�������������������������������������� 359 20-Hydroxyecdysone����������������������������������������������������� 283 6′-Hydroxyyatein������������������������������������������������������������� 15 5-Hydroxyzerumbone������������������������������������������������������ 73 Imperatorin��������������������������������������������������������������������� 358 Indigo����������������������������������������������������������������������������� 240 Indirubin������������������������������������������������������������������������� 240 Isatan B�������������������������������������������������������������������������� 241 Isoandrographolide���������������������������������������������������������� 56 Isochaihulactone������������������������������������������������������������ 355 Isocoronarin D����������������������������������������������������������������� 59 Isovitexin������������������������������������������������������������������������ 247 Jasmolactone B�������������������������������������������������������������� 334 Kaempferol���������������������������������������������������������������������� 57 Kinsenoside���������������������������������������������������������������������� 92 Kwanzoquinone A���������������������������������������������������������� 147 Lawsone������������������������������������������������������������������������� 230 Lepidine������������������������������������������������������������������������� 242 Ligustilide���������������������������������������������������������������������� 356 Linalool�������������������������������������������������������������������������� 336 Lobeline������������������������������������������������������������������������� 350 Longicalycin A��������������������������������������������������������������� 277 Lusianthridin������������������������������������������������������������������ 106 Luteolin�������������������������������������������������������������������������� 246 Lycorine����������������������������������������������������������������� 132, 144 Magnoflorine������������������������������������������������������������������ 208 Manassantin A������������������������������������������������������������������ 12 Mangiferin���������������������������������������������������������������������� 314 Maytansine��������������������������������������������������������������������� 219 Methyl eugenol�������������������������������������������������������������� 244 Methylswertianin����������������������������������������������������������� 326 4-Methylthio-3-butenyl isothiocyanate�������������������������� 244 Miogadial������������������������������������������������������������������������� 67

Chemical Structures Mistletonone������������������������������������������������������������������ 260 Monolaterol���������������������������������������������������������������������� 27 Moronic acid������������������������������������������������������������������ 260 Moscatilin���������������������������������������������������������������������� 106 Myricetin������������������������������������������������������������������������ 226 Myxopyroside���������������������������������������������������������������� 339 n-butyl-4-ol n-propyl phthalate�������������������������������������� 159 N-methyl-actinodaphnine������������������������������������������������� 18 Norcepharadione B (−)-Nordicentrine����������������������������������������������������������� 208 Nudol������������������������������������������������������������������������������ 109 Nyasol���������������������������������������������������������������������������� 135 1-O-(3-hydroxybutyryl) pancratistatin��������������������������� 164 1′-O-caffeoyl-6′-O-galloyl-beta-d-glucopyranose��������� 257 3-O-methyl kaempferol���������������������������������������������������� 72 3-O-methylquercetin�������������������������������������������������������� 79 Oenanthotoxin���������������������������������������������������������������� 371 Okundoperoxide��������������������������������������������������������������� 83 Oleanolic acid�������������������������������������������������������� 199, 270 Oleuropein���������������������������������������������������������������������� 331 Ophiopogonin D������������������������������������������������������������� 151 Orobol 7-O-d-glucoside������������������������������������������������� 230 Osthol����������������������������������������������������������������������������� 368 Ottelione A��������������������������������������������������������������������� 169 Ottelione B��������������������������������������������������������������������� 169 Ottensin���������������������������������������������������������������������������� 69 1,2,3,4,6-penta-O-galloyl-beta-d-glucose���������������������� 205 8-Phenylphenalenone������������������������������������������������������� 26 p-coumaryl alcohol���������������������������������������������������������� 43 p-hydroxycinnamaldehyde����������������������������������������������� 37 Phenylephrine������������������������������������������������������������������ 18 Paeoniflorin�������������������������������������������������������������������� 204 Paeonol��������������������������������������������������������������������������� 205 Pancratistatine�������������������������������������������������������� 132, 153 Panduratin A��������������������������������������������������������������������� 47 Parvisoflavone A�������������������������������������������������������������� 81 Parvisoflavone B�������������������������������������������������������������� 81 Persicarin������������������������������������������������������������������������ 371 Phacelioid����������������������������������������������������������������������� 346 Phellopterin�������������������������������������������������������������������� 359 Phenylimidazole������������������������������������������������������������� 242 Phillyrin������������������������������������������������������������������������� 341 Pholidotol A������������������������������������������������������������������� 123 Physcion��������������������������������������������������������������������������� 94 Pimarane diterpene����������������������������������������������������������� 39 Pinocembrin��������������������������������������������������������������������� 37 Pinoresinol diglucoside�������������������������������������������������� 312 Piperolactam A����������������������������������������������������������������� 10 Plumbagin������������������������������������������������������������������������ 75 Plumbagone�������������������������������������������������������������������� 293 Polyphillin D������������������������������������������������������������������ 154 Pregnane saponin����������������������������������������������������������� 159 Primin����������������������������������������������������������������������������� 298 Pristimerin�������������������������������������������������������������� 219, 223 Procyanidin B-1������������������������������������������������������������� 269

Chemical Structures Prodelphinidin B-2 3,3′-di-O-gallate����������������������������� 226 Progesterone������������������������������������������������������������������� 166 Protoanemonin��������������������������������������������������������������� 207 Quercetin���������������������������������������������������������������� 265, 293 Quercetin 3-rhamnoside����������������������������������������������������� 9 3-R-(−)-epicatechol�������������������������������������������������������� 267 Resveratrol����������������������������������������������������������������������� 82 Retrodihydrochalcone���������������������������������������������������� 142 Rhodanthoside A������������������������������������������������������������ 320 Rhodexin A�������������������������������������������������������������������� 158 Rosmarinic acid������������������������������������������������������������� 372 RPR112378�������������������������������������������������������������������� 168 Ruscogenin��������������������������������������������������������������������� 149 Rutin��������������������������������������������������������������������������������� 54 Saikosaponin d��������������������������������������������������������������� 366 Salaprinol����������������������������������������������������������������������� 224 Salicylic acid�������������������������������������������������������������������� 77 Sapxanthoneone������������������������������������������������������������� 287 Sarsasapogenin��������������������������������������������������������������� 135 Sauchinone����������������������������������������������������������������������� 11 Saxifragifolin B�������������������������������������������������������������� 300 Schisandrin B��������������������������������������������������������������������� 4 Schisanhenol���������������������������������������������������������������������� 2 Schisantherin A���������������������������������������������������������������� 16 Sesquiterpene glycoside of Dendrobium����������������������� 106 [6]-Shogaol���������������������������������������������������������������������� 31 [8]-Shogaol���������������������������������������������������������������������� 65

xi Sinapic acid�������������������������������������������������������������������� 238 Sinapine iodine��������������������������������������������������������������� 240 Sinigrine������������������������������������������������������������������������� 234 Swertiamarine���������������������������������������������������������������� 316 Syringaresinol-di-O-beta-d-glucoside��������������������������� 312 Syringin�������������������������������������������������������������������������� 264 Thalassiolin A���������������������������������������������������������������� 167 Thymidine���������������������������������������������������������������������� 138 Thymol��������������������������������������������������������������������������� 376 Timosaponin AIII����������������������������������������������������������� 135 Torilin����������������������������������������������������������������������������� 368 Trans-resveratrol������������������������������������������������������������ 204 Tricin�������������������������������������������������������������������������������� 77 6-Tridecylresorcylic acid����������������������������������������������� 303 Triptolide������������������������������������������������������������������������ 219 Tryptanthrin������������������������������������������������������������������� 241 Umbelliprenin���������������������������������������������������������������� 365 Ursolic acid�������������������������������������������������������������������� 285 Vanillin����������������������������������������������������������������������������� 89 Veratramine�������������������������������������������������������������������� 163 Verbascoside������������������������������������������������������������������ 332 Verticine������������������������������������������������������������������������� 145 Verticinone��������������������������������������������������������������������� 145 Vitalboside��������������������������������������������������������������������� 200 Xanthorrhizol������������������������������������������������������������� 38, 53 Xanthotoxol�������������������������������������������������������������������� 365 Zerumbone����������������������������������������������������������������������� 69

Foreword It is my pleasure to write a foreword to this book, the result of great effort to give a perspective to the biological activity of a large number of major traditional Chinese medicines. This book may be very helpful in starting new studies in this exciting field. The world has many different medical systems. This diversity is currently under much pressure because owing to globalization only a few seem to survive. Obviously, the various systems are strongly linked with cultures. Western medicine relies strongly on technology, whereas others might be more focused on the human being itself rather than on his/her blood pressure or other measurable physiological or biochemical status. Personal treatment is a very important part of the cure. A recent study showed that a treatment of asthma even with a placebo results in improved well-being of the patient when compared to a nontreated patient, even though physical measurements showed only an improvement for the drug-treated patient. While judging medicines and treatments in any system one should keep in mind the placebo effect, that is, the effect of any medicine or treatment on the mind.1 Unfortunately, it seems a general misconception in the western world that all traditional medicine has no activity, whereas all western drugs are very active. Clearly, this book shows us the richness of Chinese medicines in all kinds of biologically active compounds. Of course, as we learn from this book, for many traditional medicines there is no scientific evidence yet for activity, or when there is clear activity, no information is available on the mode of action. Moreover, the western medical world sees the use of complex mixtures as a negative aspect. Indeed that is a complicating factor as western medicines are mostly single compounds working on a single target, although the successful treatment of HIV patients with mixtures of medicines shows a change in paradigm. When criticizing traditional medicine for using mixtures one should keep in mind that in western society many elderly people are using several drugs at the same time, and in that case one may raise the same questions about how much we know about such mixtures, not to mention the placebo effect of western medicines and the misuse and serious side-effects of medicines being the cause of an estimated 15% of all hospitalizations. All this shows the complexity of traditional medicine and raises the question of how one ought to deal with this. First, we should be aware that the core of western drugs is based on Eurasian, Mediterranean traditional medicine. Morphine, atropine, and salicylic acid are very well-known examples. Drugs such as artemisin, quinine, and cocaine have their origin in traditional medicines in other parts of the world. Apparently, traditional medicine is a major source of leads for drug development. Studies on traditional medicine using the bioassay-guided fractionation approach may be a way for drug development. Although it carries the risk that well-known compounds such as salicylate or GABA are found, at least this will confirm the traditional use of the drug and could be the basis of evidence-based traditional medicine. However, for example, considering that in Chinese medicine different ingredients are mixed in a medicine by purpose, one may hypothesize that more than one active compound is present, and even synergy may play a role. Synergy may occur in many ways, on the level of the effect itself by multitargeting or on the level of pharmacokinetics by effecting metabolism, absorption, and/or excretion of the active compounds. A further complication in studies for active compounds is that prodrugs are present; that is, the real active compound is formed in the gastrointestinal tract (e.g., hydrolysis of glycosides) or in the liver (e.g., oxidation by cytochrome P450 enzymes). As already mentioned, an important aspect of traditional medicine is personalized medicines; that is, each patient gets his/her specific prescription, something western medicine so far has developed only for some very specific medications, but is now a major issue for future drug development as apparently genetic differences between individuals are clearly related to the efficacy of medicines.

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xiv

Foreword

In fact, the real evidence for the activity of traditional medicine should come from clinical trials. From proven activity one may develop a drug in the reverse way, from clinic to lead compound. This might be through the classical bioassay-guided way or using a systems biology approach in which compounds in mixtures are related to activity via, for instance, multivariate analysis. The latter approach will also identify prodrugs and synergy.2 Determining whether to use the classical or novel approach, the first step will always be the choice of plants and medicines with which to start. Rather than studying many plants superficially to prove an activity, one should focus on a few plants and prove (or disprove) their activity and safety (toxicity) and thus come to evidence-based traditional medicine and possibly also to new leads and targets for drug development. There is a window of opportunity now, and in the coming 5 years some traditional medicines must reach the status of evidence-based medicine, recognized by the Food and Drug Administration and/or the European Medicines Agency. If not, interest will disappear, funds will decrease, and one of the last chances to validate traditional medicine will be lost. To avoid this, we need to select from the present platform of basic knowledge on traditional medicine the most promising plants for further studies. This book is an excellent source for searching for candidates for such studies in the field of Chinese medicine. This compilation of information on Chinese medicinal plants is also an excellent source for those who are interested in quality control of these plants, as markers for identity as well as for activity can easily be found in this book. Prof. Dr. R. Verpoorte Natural Products Laboratory, IBL Leiden, the Netherlands

REFERENCES

1. Wechsler ME, Kelley JM, Boyd IOE, Dutile S, Marigowda G, Kirsch I, Israel E, Kaptchuk TJ, 2011, Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med; 365:119–126. 2. Verpoorte R, Choi YH, Kim HK, 2005, Ethnopharmacology and systems biology: A perfect holistic match. J Ethnopharmacol; 100:53–56.

Preface In this impressive volume, Christophe Wiart has characterized and classified medicinal plants from China, Japan, and Korea. It details some 200 medicinal plant species that have been carefully selected for their novelty and pharmacological importance. The potential of traditional Chinese medicines has been known for many thousands of years, but it is only in recent years that there has been a real drive for the globalization of this phenomenon. The real essence of the approach of traditional Chinese medicine comes from the use of complex mixtures of plant extracts that have been developed and handed down through generations. However, this complexity and variety of composition of individual traditional Chinese medicines also provide a major barrier to their acceptance and approval by regulatory agencies in the West. It is clear, however, that medicinal plants can provide an important starting point for standard drug discovery approaches where the natural occurring pharmacological agent has been identified structurally and its pharmacological actions clearly established. The major limitation in this approach is the correct identification of the medicinal plants and the characterization of the pharmacologically active molecules that they produce. This specialist volume classifies the plants according to the Angiosperm Phylogeny Group classification that is the most recognized system for classification of flowering plants. Wiart has used his pharmacological knowledge to select those plant species that are the most prominent candidates for drug discovery. The book provides the latest information on the phytochemical and pharmacological properties of each plant and should provide an excellent starting point for anyone looking to unlock the potential of these important medicinal plants. The most important aspect of this, however, will be the correct identification of the plant species. The detailed photographs and hand-made botanical plates presented in this volume will be of huge benefit. The University of Nottingham has a long-standing interest in the study of drugs from plants. This has been renewed with the establishment of a University campus at Semenyih in Malaysia, and Wiart is a member of the School of Biomedical Sciences that has recently established a formal presence at this campus. Drug discovery is a major priority for the University of Nottingham and the development of new drugs from plants will be an important part of this strategy. Prof. Stephen J. Hill Department of Molecular Pharmacology School of Biomedical Sciences University of Nottingham

xv

Author Dr. Christophe Wiart has been studying the medicinal plants of India, Southeast Asia, China, Korea, and Japan for the last 16 years. He has collected, identified, and classified several hundred species of medicinal plants and is regarded as the most prominent authority in the field of Asian ethnopharmacology, chemotaxonomy, and ethnobotany. He is based in the School of Biomedical Sciences of the University of Nottingham (Malaysia Campus), and currently supervises several PhD students working on the discovery of novel antibacterial, anticancer, antiinflammatory, and ­antioxidant agents from medicinal plants. He has authored several reference books on the medicinal plants of Asia.

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1

Superorder Austrobaileyanae (Croizat) Doweld ex M.W. Chase & Reveal, 2009*

1.1  ORDER AUSTROBAILEYALES TAKHT. EX REVEAL, 1992 The order Austrobaileyales is primitive and comprises three families of flowering plants of which the Schisandraceae is discussed here. Of interest in this clade are series of dibenzocyclooctadiene lignans that are worth studying for pharmacology for their effects on neurodegeneration, cancer, and ageing. Such lignans are particularly abundant in the Schisandraceae.

1.1.1  Family Schisandraceae Blume, 1830, nom. cons., the Schisandra Family The family Schisandraceae consists of 3 genera and about 50 species of flowering plants, found in tropical and temperate regions of eastern Asia. These are aromatic woody climbers that contain tannins and unusual series of dibenzocyclooctadiene lignans. The leaves are simple, alternate, entire, and without stipules. The flowers are small, solitary, axillary, regular, hypogynous, and with a somewhat elongated receptacle. The perianth consists of 5–24 tepals that are spirally arranged in series of 2 or more. The androecium comprises 4–80 stamens that are spirally arranged. The filaments are short. The anthers are basifixed, tetrasporangiate, and dithecal. The gynoecium comprises numerous carpels that are free and spirally arranged. Each carpel contains 2–5 marginal ovules. The fruits are berry-like and made of numerous carpels. The family is yet to be fully investigated for pharmacology. Some of the most promising species in this family are Kadsura scandens Bl. and Schisandra chinensis (Turcz.) Baill. 1.1.1.1  Kadsura scandens Bl. [From Japanese Kadsura, and from Latin scandens = climbing] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië by Karl Ludwig von Blume in 1825. Blume (1796–1862) was deputy director of agriculture in Bogor. Common names: Akar kapala patong, akar dama daura (Malay). Synonym: Kadsura cauliflora Bl. Habitat: It is a large woody climber found in the rainforests of Thailand, Malaysia, and Indonesia. Diagnosis: Kadsura scandens Bl. grows to a length of 15 m. The bark is dark, fissured, and striated. The petiole is 3 cm long. The leaves are simple, alternate, and without stipules. The blade is coriaceous, broadly ovate, round at the base, with 5 pairs of secondary nerves, and 10 cm × 6 cm to 20 cm × 12 cm. The flowers are unisexual, axillary, cauliflorous, rose pink, and 1.5 cm in diameter. The corolla comprises three sepals that are triangular and connate *

The superorder Austrobaileyanae consists of the single order Austrobaileyales.

1

2

Medicinal Plants of China, Korea, and Japan

FIGURE 1.1  Kadsura scandens Bl.

at the base. The petals are oblong, fleshy, and blunt. In male flowers, the stamens are numerous and produced from a fleshy receptacle. The carpels in female flowers are numerous too. The fruits are showy, red, sweetsop-like, glossy, fleshy, and consist of numerous carpels that are sessile, globose, beaked, and less than 1.5 cm in diameter (Figure 1.1). Medicinal uses: In Malaysia, a decoction of the roots is used to treat rheumatism. In Indonesia, this plant is used to treat cough, abdominal pain, diarrhea, skin diseases, and to excite the discharge of urine. H3C

CH3

H3CO

OCH3 H3CO

OCH3 OH

OCH3

Schisanhenol

Pharmacology: The pharmacological property of Kadsura scandens Bl. is apparently insufficiently explored yet. The plant may contain some lignans that may be involved in the antiinflammatory and antipyretic properties mentioned above. One such lignan could be schisanhenol that impaired the production of superoxide anions in the xanthine/xanthine oxidase experiment.1 Tannins that abound in members of the family Schisandraceae may be responsible for the antidiarrheal property of the plant. Note that the diuretic property of the

Superorder Austrobaileyanae (Croizat) Doweld ex M.W. Chase & Reveal, 2009

3

plant could involve lignans, as schisandrin B protected rodents against gentamicin-induced kidney damage.2 Bioresource: In vitro pharmacological study of schisanhenol for its effect on neurodegeneration. The next plant discussed in this section is Schisandra chinensis (Turcz.) Baill. 1.1.1.2  Schisandra chinensis (Turcz.) Baill. [From Greek schizein = to cleave, and andros = man, and from Latin chinensis = from China] History: This plant was first formally described in Bulletin de la Société Impériale des Naturalistes de Moscou by Nicolai Stepanovitch Turczaninow in 1837. Turczaninow (1796–1863) was a Russian botanist. Common names: Schisandra, wu wei zi (Chinese), gomishi (Japanese), nam o mi ja (Korean). Basionym: Kadsura chinensis Turcz. Synonyms: Maximowiczia amurensis Rupr., Maximowiczia chinensis (Turcz.) Rupr., Schisandra chinensis var. leucocarpa P.H. Huang & L.H. Zhuo. Habitat: It is a dioecious perennial woody climber found in the forests of China, Japan, Korea, and Russia. It is cultivated as an ornamental plant for the garden, as a culinary plant, and as a medicinal plant. Diagnosis: Schisandra chinensis (Turcz.) Baill. is 5 m long. Latex is present and the fresh leaves release a lemony smell when crushed. The petiole is 0.9–5 cm long and glabrous. The blade is obovate, 4.5 cm × 2.5 cm to 10 cm × 6.5 cm, membranaceous, and with 4–6 pairs of secondary nerves. The blade is cuneate at the base, serrulate, and shortly acuminate at the apex. The flowers are axillary and solitary. The perianth comprises 5–9 white tepals that are 0.65 cm × 0.2 cm to 1 cm × 0.5 cm and glabrous. The male flowers have 5 stamens. The female flowers comprise 15–40 carpels. The fruits are edible, pinkish red, globose, glossy, fleshy, 0.75 cm long, and grouped into a sort of grape (Figure 1.2).

FIGURE 1.2  Schisandra chinensis (Turcz.) Baill. (From Coll.: Q. Lin. Flora of China. No. 991. Academia Sinica (IBSC). Guangzhou, Guangdong, China. Hill, shattered forest cover, fertile soil. Alt.: 1250 m.)

4

Medicinal Plants of China, Korea, and Japan

Medicinal uses: In Korea, the fruits are eaten to promote digestion and the circulation of blood postpartum and to treat lung diseases and cough. In China, this plant is used to invigorate, to reduce diuresis, and to treat asthma, diarrhea, dysentery, and gonorrhea. The plant has been included in recent editions of the Russian National Pharmacopoeia. Pharmacology: Schisandra chinensis (Turcz.) Baill. abounds with lignans of pharmacological interest such as gomisin A. Gomisin A inhibited 12-O-tetradecanoylphorbol-13acetate-induced ear edema in rodents.3 Is gomisin A involved in the antiasthmatic property mentioned above? Note that gomisin A induced vasodilation of rings of rat thoracic aorta by partially activating the endothelium-dependent nitric oxide pathway; hence the use of the plant to promote blood circulation.4 Gomisin A protected rodents against acetaminophen-induced hepatocellular damage.5 Another hepatoprotective lignan isolated from this plant is schisandrin B that protected rodents against CCl4-induced hepatocellular damage by a mechanism involving mitochondrial glutathione redox.6 In addition, schisandrin B intensified the passive avoidance-response in rodents as assessed by the step-through task experiment.7 H3C

H3C

CH3 OH

OCH3

O O

OCH3

OCH3 OCH 3

Gomisin A

CH3

OCH3

O O

OCH3

OCH3

OCH3

Schisandrin B

Schisandrin B protected myocardial ischemia-reperfusion injury partly by inducing heat shock protein 25 and heat shock protein 70 expression in rodents.8 Besides, schisandrin B inhibited P-glycoprotein-mediated drug efflux that is one of the principal causes of cancer multidrug resistance.9 Furthermore, schisandrin B lowered hepatic cholesterol and triglyceride levels (by up to 50% and 52%, respectively) in rodents suffering from experimentally induced hypercholesterolemia.10 Finally, schisandrin B, given orally at a dose of 10 mg/kg/day, protected rodents against mercury poisoning.11 The lignans deoxyschisandrin, gomisin N, and wuweizisu C protected cultured rat cortical neurons against glutamate-induced cellular damage.12 Schisantherin C displayed a cytotoxic effect against human lung adenocarcinoma epithelial (A549) cells cultured in vitro.13 Tannins that abound in members of the family Schisandraceae may be responsible for the antidiarrheal and antidysentery properties mentioned earlier. Bioresource: In vitro pharmacological study of schisantherin C for its effect on lung cancer. Lignans of pharmaceutical interest are found in the next clade: the superorder Magnolianae, discussed in Chapter 2.

REFERENCES

1. Lu H, Liu GT, 1992, Antioxidant activity of dibenzocyclooctene lignans isolated from Schisandraceae. Planta Med; 58(4):311–313.

Superorder Austrobaileyanae (Croizat) Doweld ex M.W. Chase & Reveal, 2009

5

2. Chiu PY, Leung HY, Ko KM, 2008, Schisandrin B enhances renal mitochondrial antioxidant status, functional and structural integrity, and protects against gentamicin-induced nephrotoxicity in rats. Biol Pharm Bull; 31(4):602–605. 3. Yasukawa K, Ikeya Y, Mitsuhashi H, Iwasaki M, Aburada M, Nakagawa S, Takeuchi M, Takido M, 1992, Gomisin A inhibits tumour promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Oncology; 49(1):68–71. 4. Park JY, Lee SJ, Yun MR, Seo KW, Bae SS, Park JW, Lee YJ, Shin WJ, Choi YW, Kim CD, 2007, Gomisin A from Schisandra chinensis induces endothelium-dependent and direct relaxation in rat thoracic aorta. Planta Med; 73(15):1537–1542. 5. Yamada S, Murawaki Y, Kawasaki H, 1993, Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats. Biochem Pharmacol; 46(6):1081–1085. 6. Ip SP, Poon MK, Che CT, Ng KH, Kong YC, Ko KM, 1996, Schisandrin B protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione redox status in mouse liver. Free Radic Biol Med; 21(5):709–712. 7. Pan SY, Han YF, Carlier PR, Pang YP, Mak DH, Lam BY, Ko KM, 2002, Schisandrin B protects against tacrine-and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice. Planta Med; 68(3):217–220. 8. Chiu PY, Ko KM, 2004, Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats. Mol Cell Biochem; 266(1–2):139–144. 9. Qiangrong P, Wang T, Lu Q, Hu X, 2005, Schisandrin B a novel inhibitor of P-glycoprotein. Biochem Biophys Res Commun; 335(2):406–411. 10. Pan SY, Dong H, Zhao XY, Xiang CJ, Fang HY, Fong WF, Yu ZL, Ko KM, 2008, Schisandrin B from Schisandra chinensis reduces hepatic lipid contents in hypercholesterolaemic mice. J Pharm Pharmacol; 60(3):399–403. 11. Stacchiotti A, Li Volti G, Lavazza A, Schena I, Aleo MF, Rodella LF, Rezzani R, 2011, Different role of Schisandrin B on mercury-induced renal damage in vivo and in vitro. Toxicology; 286(1–3):48–57. 12. Kim SR, Lee MK, Koo KA, Kim SH, Sung SH, Lee NG, Markelonis GJ, Oh TH, Yang JH, Kim YC, 2004, Dibenzocyclooctadiene lignans from Schisandra chinensis protect primary cultures of rat cortical cells from glutamate-induced toxicity. J Neurosci Res; 76(3):397–405. 13. Min HY, Park EJ, Hong JY, Kang YJ, Kim SJ, Chung HJ, Woo ER et al., 2008, Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells. Bioorg Med Chem Lett; 18(2):523–526.

2

Superorder Magnolianae Takht., 1967

The superorder Magnolianae consists of the orders Piperales, Canellales, Magnoliales, Chloranthales, and Laurales. These living fossils and the Austrobaileyanae, with which they share the ability to produce lignans, have a common ancestor. Magnolianae are chemically characterized by their ability to accumulate substantial amounts of isoquinoline alkaloids. The evidence gathered so far clearly indicates that members of this clade provide isoquinolines and/or lignans that should undergo more pharmacological studies in the field of oncology, microbiology, parasitology, and neurology. Cytotoxic: The isoquinoline alkaloid neolitsine isolated from Cassytha filiformis L. (order Laurales, family Lauraceae) abrogated the survival of human epithelial cervical cancer (Hela) and mouse embryonic fibroblast (3T3) cells cultured in vitro.1 Members of the genus Goniothalamus (Blume) Hook. f. & Thomson (order Magnoliales, family Annonaceae) augment a styryllactone that disrupted intracellular redox balance and induced cdc25C degradation in human breast cancer (MDA-MB231) cells cultured in vitro.2 The monotetrahydrofuran gamma-lactone longifolicin isolated from the leaves and stems of Asimina longifolia Kral (order Magnoliales, family Annonaceae) was dramatically cytotoxic against human pancreatic carcinoma cells cultured in vitro with an IC50 value below 10−7 μg/mL.3 A lignan isolated from Magnolia officinalis Rehder & E.H. Wilson (order Magnoliales, family Magnoliaceae) abrogated the survival of human erythromyeloblastoid leukemia (K562), human epithelial cervical cancer (Hela), and human lung adenocarcinoma epithelial (A549) cells cultured in vitro with IC50 values of 3.9, 1.5, and 3.7 μg/mL, respectively.4 The alkaloid boldine isolated from Peumus boldus Molina (order Laurales, family Monimiaceae) may have some effect on brain cancer as it inhibited the growth of human neuronal glioblastoma (U138-MG), human glioblastoma-astrocytoma (U87-MG) cells, and mouse glioma (C6) cells at doses of 80, 250, and 500 μM, respectively.5 Sesquiterpenes isolated from the bark and leaves of Zygogynum pancheri (Baill.) Vink and Zygogynum acsmithii Vink (order Canellales, family Winteraceae) abrogated the survival of several cancer cell-lines cultured in vitro.6 The lignan (−)-dihydroguaiaretic acid ­isolated from the roots of Endiandra anthropophagorum Domin (order Laurales, family Lauraceae) exhibited a potent cytotoxic effect against human lung adenocarcinoma epithelial (A549) cells with an IC50 value of 7.4 μM.7 Another magnolianaeous alkaloid of interest is (+)-N-(2hydroxypropyl)lindcarpine isolated from Actinodaphne pruinosa Nees (order Laurales, family Lauraceae) that exhibited cytotoxic activity against mouse leukemia (P388) cells with an IC50 value of 3.9 μg/mL.8 Antibacterial, antifungal: Unusual series of phenanthrenes alkaloids, such as sampagine, ­isolated from Eupomatia species (order Magnoliales, family Eupomatiaceae) with strong antifungal, antimycobacterial, and cytotoxic properties have been reported.9 The 2,3-­­dihydrobenzofurans eupomatenoid-3 and eupomatenoid-5 isolated from the leaves of Piper regnellii (Miq.) C. DC. (order Piperales, family Piperaceae) abrogated the survival of the dermatophyte fungi Trichophyton rubrum cultured in vitro.10 The lignan licarin A isolated from Aristolochia taliscana Hook. & Arn. (order Piperales, family Aristolochiaceae) exhibited a potent antimycobacterial activity in vitro.11 7

8

Medicinal Plants of China, Korea, and Japan

Parasiticidal: A dichloromethane extract of bark of Warburgia salutaris (Bertol.) Chiov. (order Canellales, family Canellaceae) abrogated the survival of Trypanosoma brucei with an IC50 value of 10.6 μg/mL on probable account of sesquiterpenes.12,13 Antiviral: The flavonoid lawinal isolated from members of the genus Desmos Lour. (order Magnoliales, family Annonaceae) inhibited the replication of the human immunodeficiency virus cultured in H9 lymphocytes with an IC50 value of 0.02 μg/mL.14 The flavans (+)-myristinins A and D isolated from Knema elegans Warb. (order Magnoliales, family Myristicaceae) inhibited the enzymatic activity of DNA polymerase in vitro.15 Central nervous system: The tetracyclic piperidine alkaloid himbacine isolated from the bark of Galbulimima belgraveana Bailey (order Magnoliales, family Himantandraceae) displayed a potent muscarinic antagonistic effect.16 The sesquiterpenes polygodial and drimanial isolated from the bark of Drymis winteri Forst. (order Canellales, family Winteraceae) exhibited antinociceptive and central analgesic effects.17 Cosmetics: The isoquinoline alkaloid cepharadione B isolated from Houttuynia cordata Thunb. (order Piperales, family Saururaceae) inhibited the enzymatic activity of tyrosinase with an IC50 value of 170 μM.18 Some of the most interesting alkaloids and lignans are found in the orders Laurales and Piperales, discussed in this chapter.

2.1  ORDER PIPERALES BERCHT. & J. PRESL, 1820 The order Piperales consists of five families of flowering plants of which the Saururaceae is ­discussed here.

2.1.1  Family Saururaceae F. Voigt in L.C.M. Richard, 1811, nom. cons., the Lizard’s-Tail Family The family Saururaceae consists of 4 genera and 7 species of rhizomatous herbs found in eastern Asia and North America. These are aromatic, perennial, tanniferous herbaceous plants with simple, alternate, and stipulated leaves. The inflorescence is a densely flowered, terminal, bracteate spike or a raceme. The flowers are tiny, perfect, hypogynous, and without perianth. The androecium consists of 6–8 stamens arranged in two alternating whorls. The filaments are slender. The anthers are large, tetrasporangiate, dithecal, and open by longitudinal slits. The gynoecium consists of 3–5 carpels that are free or united to form a compound unilocular ovary with parietal placentation. The fruits are somewhat fleshy and made of a single- or many-seeded carpels. The seeds are minute. The pharmacological potentials of this family are yet to be explored. The family produces ­lignans, alkaloids, and flavonoids of pharmacological interest. Houttuynia cordata Thunb. is discussed next. 2.1.1.1  Houttuynia cordata Thunb. [After Dutch biologist Maarten Houttuyn (1720–1798), and from Latin cordata = heart-shaped] History: This plant was first formally described in Kongl. Vetenskaps Academiens Nya Handlingar by Carl Peter Thunberg in 1783. Thunberg (1743–1828) was a Swedish botanist. Common names: Chameleon plant, heartleaf, bishop’s weed, ji cai (Chinese), dokudami (Japanese), yak mo mil (Korean). Synonyms: Polypara cochinchinensis Lour., Polypara cordata Kuntze. Habitat: It is an invasive perennial herb found in China, Taiwan, Bhutan, India, Indonesia, Japan, Korea, Burma, Nepal, and Thailand. It is cultivated as an ornamental plant for ­gardens and a as a culinary plant.

9

Superorder Magnolianae Takht., 1967

FIGURE 2.1  Houttuynia cordata Thunb. (From Coll.: K. C. Jain and R. C. Bharadwaja. Herbarium of the Forest Research Institute, Dehra Dun, India. Plants of Kulu Valley. Date: 1950.)

Diagnosis: Houttuynia cordata Thunb. grows to a height of 70 cm. The rhizome is creeping, thin, and edible. The stems are creeping and stoloniferous. The stipular sheath is 1–2.5 cm long and ciliate. The fresh leaves have a peppery scent when crushed. The petiole is 1–3.5 cm long. The blade is edible, spear-shaped, 2.5 cm × 5.5 cm, papery, densely glandular, purplish below, cordate at the base, shortly acuminate at the apex, and has 5–7 pairs of secondary nerves. The inflorescence is 2.5 cm × 0.5 cm. The involucral bracts are oblong, 1.5 cm long, pure white, and round at the apex. The fruits are capsular, 0.25 cm long, and present persistent styles (Figure 2.1). Medicinal uses: In China, this plant is used to check hemoptysis, to heal hemorrhoids, to break fever, to treat infection, skin diseases, bone injury, tumors, costiveness, indigestion, diarrhea, intoxication, and inflamed swellings. It is also used to heal abscesses, wounds, and to expel worms from the intestine. In Cambodia, Laos, and Vietnam, this plant is used to induce menses and to treat dysentery, measles, inflammation of the eyes, and urticaria. Pharmacology: The essential oil distilled from this plant contains methyl n-nonyl ketone, lauryl aldehyde, and capryl aldehyde that abrogated the survival of the herpes simplex virus, influenza virus, and human immunodeficiency virus cultured in vitro.19 Besides, an extract of the plant abrogated the survival of the herpes simplex virus cultured in vitro20 on OH OH O

HO

O OH

O

O

OH OH

Quercetin 3-rhamnoside

OH

OH

10

Medicinal Plants of China, Korea, and Japan

probable account of norcepharadione B.18,20 In addition, quercetin 3-rhamnoside extracted from the plant abrogated the survival of the influenza virus cultured in vitro.21 An extract of the plant inhibited human colon adenocarcinoma (HT-29) cell survival via apoptosis induction on probable account of alkaloids.22 This plant contains alkaloids such as aristolactam B, piperolactam A, aristolactam A, norcepharadione B, cepharadione B, and splendidine that exhibited some levels of cytotoxic activities against human lung adenocarcinoma epithelial (A-549), human ovary adenocarcinoma (SK-OV-3), human skin melanoma (SK-MEL-2), and human colorectal adenocarcinoma (HCT-15) cells cultured in vitro.23 O

O H3CO

N3 O

H3CO

H3CO

HO

OH

O

NH

NH

O

N NH

H3C O Piperolactam A

Norcepharadione B

AZT

The anti-inflammatory property of this plant is confirmed: an extract of the plant curbed the inflammation induced by carrageenan in the rat pleurisy experiment.24 This property could be owed to the flavonoids quercitrin and quercetin-3-O-beta-D-galactopyranoside that showed noteworthy antioxidant effects in the 2,2-diphenyl–1-picrylhydrazyl experiment.18 Note that polyphenols isolated from the leaves abrogated bovine serum albumin fragmentation by copper–hydrogen peroxide.25 Polyphenols may account for the astringent and styptic uses of the plant. Another anti-inflammatory material involved here could be the essential oil that inhibited the release of lipopolysaccharideinduced prostaglandin E2 from mouse peritoneal macrophages with an IC50 value of 44.8 μg/mL. Moreover, the essential oil inhibited the enzymatic activity of cyclooxygenase-2 with an IC50 value of 30.9 μg/mL.26 An extract of the plant boosted the multiplication of mouse splenic lymphocytes dosedependently and inhibited the enzymatic activity of the severe acute respiratory syndrome-associated coronavirus-like protease and RNA-dependent RNA polymerase.27 An extract of the plant exhibited antibacterial effects against murine salmonellosis, and hence the antiseptic use of the plant.28 Bioresource: In vitro pharmacological study of norcepharadione B for its effect on human immunodeficiency virus infection. Aristolactams probably account for the antibacterial property of the plant and are found in Saururus chinensis (Lour.) Baill., discussed next. 2.1.1.2  Saururus chinensis (Lour.) Baill. [From Latin Saururus = reptile’s tail, and chinensis = from China] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Chinese lizard’s tail, san bai cao (Chinese), hangesho (Japanese), sam baek cho (Korea). Basionym: Spathium chinense Lour. Synonyms: Saururopsis chinensis (Lour.) Turcz., Saururopsis cumingii C. DC., Saururus ­cernuus Thunb., Saururus loureiri Decne. Habitat: It is a perennial herb found in wet places in China, Taiwan, India, Japan, Korea, the Philippines, and Vietnam.

11

Superorder Magnolianae Takht., 1967

FIGURE 2.2  Saururus chinensis (Lour.) Baill. (From Coll.: Y. Tsiang. Det.: D. Merrill. Flora of Kwangtung. Herbarium of the College of Agriculture. Sun Yatsen University, Canton. No. 2065. In pool, herb 70 cm high. Loc.: Kochow district, near Sing-tung. Date: May 4, 1929.)

Diagnosis: Saururus chinensis (Lour.) Baill. grows to a height of more than 1 m. The rhizome is creeping, white, and thick. The stems are creeping at the base and erect at the apex. The stipular sheath is 0.2–1 cm long and slightly clasping. The petiole is 1–3 cm long and glabrous. The blade is spear shaped, 10 cm × 5 cm to 20 cm × 10 cm, papery, densely glandular, cordate at the base, and acute at the apex; it has 5–7 pairs of secondary nerves and a whitish patch at the base. The inflorescence is an elongated, curved, 10–20 cm long, taillike whitish spike. The flowers are minute and innumerable. The bract beneath each flower is spatulate. The filaments are longer than the anthers. The fruits are globose, 0.25 cm in diameter, and tuberculate (Figure 2.2). Medicinal uses: In China, this plant is used to excite the discharge of urine, diuretic, to treat infection, malaria, to heal abscesses, to expel worms from the intestines, and affords a laxative remedy. In Cambodia, Laos, and Vietnam, the leaves are made into a paste that is applied to wounds and ulcers. Constituents: The plant contains series of lignans such as sauchinone, saucernetin-7, saucerneol D, 2′-hydroxydihydroguaiaretic acid, machilin D, and manassantin A.29 Pharmacology: The anti-inflammatory property of the plant is confirmed: the lignan saucerneol D protected rodents against airway hyper-responsiveness in the ovalbumin aerosol experiment and inhibited the production of immunoglobulin E.30 Oral administration of an extract of leaves of Saururus chinensis (Lour.) Baill. protected rodents against the development of atopic dermatitis-like skin lesions induced by picryl chloride confirming the healing property of the plant.31 CH3 H3C H

O

O H

H O

O

O

Sauchinone

O

12

Medicinal Plants of China, Korea, and Japan

Sauchinone protected rats against CCl4-induced hepatocellular damage29 and inhibited the induction of apoptosis of mouse glioma (C6) cells by staurosporine.32 Saucernetin-7 potently compromised the proliferation of human promyelocytic leukemia (HL-60) cells.33 H3C

CH3 HO

CH3

CH3

O O

O OCH3

OH

OCH3

OCH3

H3CO OCH3

OCH3 Manassantin A

Saucerneol D inhibited the enzymatic activity of DNA topoisomerase I and II34 and could be responsible for the parasiticidal effect of the plant.35 Manassantin A exhibited cytotoxic activities against human hepatocellular carcinoma (SK-Hep-1), human prostate cancer (PC-3), human prostate carcinoma (DU-145), human ductal breast epithelial tumor (T-47D), human epithelial cervical cancer (Hela), and human skin melanoma (SK-MEL-2) cells cultured in vitro via apoptosis induction.36,37 Note that manassantin A exhibited an immunosuppressive effect in vitro38 and inhibited cAMPinduced melanin production in B16 melanoma cells.39 Besides, 2′-hydroxydihydroguaiaretic acid and machilin D showed an antioxidant effect in the thiobarbituric acid reactive substances experiment with IC50 values of 3.3 and 3.8 μM, respectively.40 The aristolactam alkaloid aristolactam BII isolated from this plant protected cultured primary rat cortical neurons against glutamate-induced cellular damage.41 Bioresource: In vitro pharmacological study of manassantin A for its effect on cancer. Alkaloids abound in the next clade: the order Laurales, discussed in the following section.

2.2  ORDER LAURALES JUSS. EX BERCHT. & J. PRESL, 1820 The order Laurales comprises seven families of flowering plants of which the Hernandiaceae and Calycanthaceae are discussed here.

2.2.1  Family Calycanthaceae Lindl., 1819, nom. cons., the Strawberry Shrub Family The family Calycanthaceae consists of 3 genera and 6 species of shrubs or treelets, confined to China and temperate North America. Calycanthaceae are aromatic and produce unusual series of pyrrolidinoindoline alkaloids such as calycanthine, calycanthidine, and folicanthine. The leaves are simple, opposite and without stipules. The flowers are large with an urceolate hypanthium. The perianth comprises 15–30 tepals that are spirally arranged on the outside of the hypanthium. The androecium consists of 5–30 stamens that are spirally arranged at the top of the hypanthium. Inside the fertile stamens, 10–25 staminodes are present. The gynoecium comprises 5–35 carpels that are distinct and spirally arranged within the hypanthial cup. The style is elongate, filiform, and presents a dry decurrent stigma. The fruits consist of numerous achenes enclosed in an enlarged, fleshy, and oily hypanthium. The seeds are poisonous.

13

Superorder Magnolianae Takht., 1967 H3C H3C NH

H

N

N

NH H3C

N

N

N CH3

Calycanthine

N H

H

CH3

Calycanthidine

Calycanthine inhibits the release of gamma amino butyric acid.42 This alkaloid is found in Chimonanthus praecox (L.) Link, described next. 2.2.1.1  Chimonanthus praecox (L.) Link [From Greek cheimon = winter, and anthos = flower, and from Latin praecox = early] History: This plant was first formally described in Species Plantarum, Editio Secunda by Carl Linnaeus in 1762. Linnaeus (1707–1778) was a Swedish botanist. Common names: Winter sweet, la mei (Chinese), ro bai (Japanese). Basionym: Calycanthus praecox L. Synonyms: Butneria praecox (L.) C.K. Schneid., Chimonanthus baokanensis D.M. Chen & Z.L. Dai, Chimonanthus baokanensis var. yupiensis D.M. Chen & Z.L. Dai, Chimonanthus caespitosus T.B. Chao et al., Chimonanthus fragrans Lindl., Chimonanthus fragrans var. grandiflorus Lindl., Chimonanthus parviflorus Raf., Chimonanthus praecox var. concolor Makino, Chimonanthus praecox var. grandiflorus (Lindl.) Makino, Chimonanthus praecox var. intermedius Makino, Chimonanthus praecox var. reflexus B. Zhao, Chimonanthus yunnanensis W.W. Sm, Meratia fragrans Loisel., Meratia praecox (L.) Rehder & E.H. Wilson, Meratia yunnanensis (W.W. Sm) S.Y. Hu. Habitat: This elegant deciduous shrub is native to Japan and cultivated through most of China as well as in other temperate areas of the world as a decorative plant, particularly for its sweetly fragrant flowers. Diagnosis: Chimonanthus praecox (L.) Link grows to a height of 15 m. The stems are grayish brown and lenticelled. The buds are axillary. The bud scales are circular, imbricate and hairy. The petiole is 0.3–1.5 cm long and hairy. The blade is elliptical, 5 cm × 2 cm to 30 cm × 15 cm, papery, with 4–6 pairs of secondary nerves, a round base, and an acute apex. The flowers are solitary, 1.5–4.5 cm in diameter, and sweetly fragrant. The flower pedicel is 0.5 cm long. The perianth comprises 15–20 yellowish white tepals that are 0.5 cm × 0.5 cm to 2 cm × 1.5 cm. The outer tepals are orbicular, puberulent, and round at the apex; the median tepals are elliptical; and the inner tepals are orbicular. The androecium comprises 5–8 stamens that are 0.4 cm long. The filaments are broad. The anthers are glabrous. The 2–15 staminodes are subulate, 0.3 cm long, and hairy. The gynoecium comprises 5–15 carpels that are hirtellous at the base. The pseudocarp is urceolate, 2 cm × 1 cm to 5 cm × 2.5 cm, woody, constricted at the apex, and with 9 or 10 apical appendages. The 3–10 achenes are brown, elliptical, 1.5 cm × 0.5 cm, and hairy at the base (Figure 2.3). Medicinal uses: In China, the flowers boiled in water provide a liquid that is drunk to sooth sore throat. Dipped in oil, the flowers are applied to burns. The dried leaves are used to stimulate the secretion of saliva. Pharmacology: The alkaloids calycanthine and folicanthine isolated from an extract of seeds showed remarkable antifungal activities against plant pathogenic fungi Exserohilum

14

Medicinal Plants of China, Korea, and Japan

FIGURE 2.3  Chimonanthus praecox (L.) Link. (From Herbarium Florae Sinensis. Comm. Ex Herb Inst. Bot. Austro-Sinensis. Academiae Sinicae. Loc.: Canton, China; Shantung Taishan, China. Date: July 23, 1963.)

turcicum, Bipolaris maydis, Alternaria solani, Sclerotinia sderotiorum, and Fusarium oxysportium cultured in vitro.43 Note that some pyrrolidinoindoline alkaloids are analgesic and may account for the medicinal uses mentioned above. H3C H3C

H

N

N

N N

CH3

H

CH3 Folicanthine

One such alkaloid is hodgkinsine isolated from Psychotria sp. (order Gentianales, family Rubiaceae) that induced a dose-dependent, naloxone reversible, analgesic effect in the thermal and capsaicin-induced pain experiments.44 The bitterness of the flowers might account for the sialagogue effect of the plant or a stimulation of the muscarinic receptor might be involved. One might be curious to investigate the parasympathomimetic property of calycanthine and folicanthine. Bioresource: In vitro pharmacological study of folicanthine for its effect on Alzheimer’s disease. Alkaloids abound in the next clade: the family Hernandiaceae.

15

Superorder Magnolianae Takht., 1967

2.2.2  Family Hernandiaceae Blume, 1826, nom. cons., the Hernandia Family The family Hernandiaceae consists of 4 genera and about 60 species of trees, shrubs, or climbers that are widespread in tropical regions. Hernandiaceae commonly produce lignans, benzylisoquinoline, and aporphine alkaloids. The leaves are alternate, simple, or compound and without stipules. The inflorescence is a cyme. The perianth consists of 4–8 imbricate tepals arranged in a single whorl. The androecium comprises 3–5 stamens arranged in a single whorl and alternate with the tepals. The filaments present a pair of basal nectariferous appendages. The anthers open by 2 valves. The gynoecium consists of a single carpel folded to form a unilocular ovary. The fruits are dry, winged, and enclose a single seed. An example of Hernandiaceae is Hernandia ovigera L. that is grown as a tropical street-tree. Hernandiaceae abound with bioactive isoquinolines and cytotoxic lignans such as podophyllotoxin. 7′-Acetylpicropodophyllin and epiyangambin isolated from Hernandia ovigera L. compromised the transformation of murine epidermal (JB6) cells cultured in vitro with IC50 values of 0.15 and 0.4 μg/ mL, respectively.45 6′-Hydroxyyatein, (−)-hernone and nymphone abrogated the survival of mouse leukemia (P-388), human nasopharyngeal carcinoma (KB), human lung adenocarcinoma epithelial (A549), and human colon cancer (HT-29) cells cultured in vitro.46 The plants discussed in this section include Illigera appendiculata Bl and Illigera luzoniensis (Presl) Merr. H3C

O

O

O HO

HO

O

H O

O O

O

OH

O O

H

H3CO

O

OCH3 OCH3 6′-Hydroxyyatein

O

OCH3

H3CO OH Etoposide

2.2.2.1  Illigera appendiculata Bl. [After Johann Karl Wilhelm Illiger (1775–1813), director of the Zoological Museum in Berlin, and from Latin appendiculata = having appendages] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië by Karl Ludwig von Blume in 1826. Blume (1796–1862) was deputy director of agriculture in Bogor. Common name: Maralipit (Malay). Habitat: It is a climber found in the forests of India, Burma, Malaysia, and Indonesia. Diagnosis: Illigera appendiculata Bl. grows to a height of 20 m. The leaves are trifoliate. The petiole is 10 cm long. The leaflets are membranaceous, pale green, ovate, rough beneath, acute at the apex, with 2–3 nerves, and 9 cm × 15 cm to 16.5 cm × 10 cm. The petiolule is 0.52 cm long. The inflorescence is a lax and 20-cm-long panicle. The flowers are 0.6 cm long, with 5 oblong pale-pink petals. The calyx is puberulous, pale pink with darker margins, tubular, and constricted above the ovary. The androecium

16

Medicinal Plants of China, Korea, and Japan

FIGURE 2.4  Illigera appendiculata Bl. (From Coll.: N. P. Balakrishnan. Botanical Survey of India. Andaman–Nicobar Circle, Port Blair. Flora of South Andamans. No. 646. Loc.: Andamans, Beadonabad, edges of forests. Date: November 30, 1973.)

comprises 10 staminodes. The fruits are oblong with a pair of broad wings that are 0.5 cm long (Figure 2.4). Medicinal uses: In Malaysia, a paste of leaves is applied to boils and rheumatism. Pharmacology: Apparently unknown. The anti-inflammatory property could involve some fatty acid derivatives such as coriolic acid and glycerol 1-monolinolate extracted from Hernandia ovigera L. that inhibited the enzymatic activity of cyclooxygenase-2.47 Other possible anti-inflammatory candidates could be some isoquinoline alkaloids as boldine isolated from Peumus boldus Molina (order Laurales, family Monimiaceae) displayed anti-inflammatory activity in the carrageenan-induced paw edema experiment with an oral ED50 value of 34 mg/kg.48 Lignans could be involved as well, as schisantherin A isolated from the fruits of Schisandra sphenanthera Rehder & E.H. Wilson (family Schisandraceae, order Austrobaileyales) impaired the generation of cytokines by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.49 HO

CH3 CH3

O O COOH

OH Schisantherin A

H3CO

O H3CO

OCH3

OCH3

O

Coriolic acid

Bioresource: In vitro pharmacological study of actinodaphnine for its effect on acne. Isoquinolines may account for the antiseptic property mentioned above. Such alkaloids could be actinodaphnine and N-methyl actinodaphnine that exhibited dramatic antibacterial activities in vitro against Gram-positive Bacillus cereus, Micrococcus sp., and Staphylococcus aureus.50 Such alkaloids occur in Illigera luzoniensis (Presl) Merr., discussed next.

Superorder Magnolianae Takht., 1967

17

2.2.2.2  Illigera luzoniensis (Presl) Merr. [After Johann Karl Wilhelm Illiger (1775–1813), director of the Zoological Museum in Berlin, and from Latin luzoniensis = from Luzon] History: This plant was first formally described in Reliquiae Haenkeanae by Karel Boriwog Presl in 1835. Presl (1794–1852) was a Czechoslovakian botanist. Common name: Tai wan qing teng (Chinese). Synonyms: Henschelia luzonensis C. Presl, Gronovia ternata Blco., Illigera meyeniana Kunth ex Walpers, Illigera pubescens Merr., Illigera ternata (Blco.) Dunn. Habitat: It is a climber found in the forests of Taiwan, Japan, and the Philippines. Diagnosis: The stems of the Illigera luzoniensis (Presl) Merr. are angular and sappy. The leaves are 3 foliolate. The petiole is 4.5–10 cm long, rugose, and hairy. The petiolules are 0.5–1.5 cm long. The blade is papery, broadly ovate, 3.5 cm × 3 cm to 15 cm × 10 cm, with 3–5 nerves, round at the base, and acute at the apex. The inflorescence is an axillary cyme that is 5–15 cm long and hairy. The flowers are green. The outer tepals are 1 cm × 0.3 cm to 1.5 cm × 0.5 cm and the inner tepals are densely hairy. The filaments are 0.75 cm long. The ovary is tetragonous and hairy. The fruits have 2–4 wings, with the largest wings being 2.5 cm wide (Figure 2.5). Medicinal use: In the Philippines, the sap from the stems is ingested to treat headache.

FIGURE 2.5  Illigera luzoniensis (Presl) Merr. (From Coll.: G. Edano. Flora of the Philippines. Herbarium, Bureau of Science. No. 77860. Loc.: Philippines, Talimbobong, Palawan. Date: June 1929.)

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Medicinal Plants of China, Korea, and Japan

Pharmacology: The plant abounds with isoquinoline alkaloids that may account for its  medicinal property. Such alkaloids are actinodaphnine, launobine, dicentrine N-methyl-actinodaphnine, O-methylbulbocapnine, and liriodenine that inhibited the aggregation of platelets. Besides, actinodaphnine and O-methylbulbocapnine induced strong vasodilation.51 The isoquinoline alkaloid N-methyl-actinodaphnine isolated from Illigera luzoniensis (Presl) Merr. is a selective alpha1-adrenoceptor antagonist that could account for the medicinal property of the plant 52,53 as it is able to reduce blood pressure. Isoquinolines are often cytotoxic and one might be curious to look for anticancer isoquinolines or lignans in this plant. The lignan (−)-deoxypodophyllotoxin abrogated the survival of human colon carcinoma DLD-1, human leukemic lymphoblast CCRF-CEM, human promyelocytic leukemia HL-60, and human neuroblastoma ­I MR-32 cells with IC50 values of 0.0057, 0.0067, 0.00004, and 0.0035 μg/mL, respectively.54 O NH

O

H3CO OH Actinodaphnine OH HO

O N

O

CH3

HN

CH3

H3CO OH N-methyl-actinodaphnine

Phenylephrine

Bioresource: In vitro pharmacological study of N-methyl-actinodaphnine for its effect on alopecia. Cytotoxic agents are common in the next clade: the superorder Lilianae, discussed in Chapter 3.

REFERENCES

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Superorder Magnolianae Takht., 1967

19

3. Ye Q, Alfonso D, Evert D, McLaughlin JL, 1996, Longifolicin, longicoricin, and gigantetroneninone, three novel bioactive mono-tetrahydrofuran annonaceous acetogenins from Asimina longifolia (annonaceae). Bioorg Med Chem; 4(4):1537–1545. 4. Youn UJ, Chen QC, Jin WY, Lee IS, Kim HJ, Lee JP, Chang MJ, Min BS, Bae KH, 2007, Cytotoxic lignans from the stem bark of Magnolia officinalis. J Nat Prod; 70(10):1687–1689. 5. Gerhardt D, Horn AP, Gaelzer MM, Frozza RL, Delgado-Cañedo A, Pelegrini AL, Henriques AT, Lenz G, Salbego C, 2008, Boldine: A potential new antiproliferative drug against glioma cells. Invest New Drugs; 27(6):517–525. 6. Allouche A, Apel C, Martin MT, Dumontet V, Guéritte F, Litaudon M, 2009, Cytotoxic sesquiterpenoids from Winteraceae of Caledonian rainforest. Phytochem; 70(4):546–553. 7. Davis RA, Barnes EC, Longden J, Avery VM, Healy PC, 2009, Isolation, structure elucidation and cytotoxic evaluation of endiandrin B from the Australian rainforest plant Endiandra anthropophagorum. Bioorg Med Chem; 17(3):1387–1392. 8. Rachmatiah T, Mukhtar MR, Nafiah MA, Hanafi M, Kosela S, Morita H, Litaudon M, Awang K, Omar H, Hadi AH, 2009, (+)-N-(2-hydroxypropyl)lindcarpine: A new cytotoxic aporphine isolated from Actinodaphne pruinosa Nees. Molecules; 14(8):2850–2856. 9. Kluza J, Mazinghien R, Degardin K, Lansiaux A, Bailly C, 2005, Induction of apoptosis by the plant alkaloid sampangine in human HL-60 leukemia cells is mediated by reactive oxygen species. Eur J Pharmacol; 525(1–3):32–40. 10. Koroishi AM, Foss SR, Cortez DA, Ueda-Nakamura T, Nakamura CV, Dias Filho BP, 2008, In vitro antifungal activity of extracts and neolignans from Piper regnellii against dermatophytes. J Ethnopharmacol; 117(2):270–277. 11. León-Díaz R, Meckes M, Said-Fernández S, Molina-Salinas GM, Vargas-Villarreal J, Torres J, LunaHerrera J, Jiménez-Arellanes A, 2010, Antimycobacterial neolignans isolated from Aristolochia taliscana. Mem Inst Oswaldo Cruz; 105(1):45–51. 12. Nibret E, Ashour ML, Rubanza CD, Wink M, 2010, Screening of some Tanzanian medicinal plants for their trypanocidal and cytotoxic activities. Phytother Res; 24(6):945–947. 13. Mahmoud II, Kinghorn AD, Cordell GA, Farnsworth NR, 1980, Potential anticancer agents. XVI. Isolation of bicyclofarnesane sesquiterpenoids from Capsicodendron dinisii. J Nat Prod; 43(3):365–371. 14. Wu JH, Wang XH, Yi YH, Lee KH, 2003, Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos. Bioorg Med Chem Lett; 13(10):1813–1815. 15. Deng JZ, Starck SR, Li S, Hecht SM, 2005, (+)-Myristinins A and D from Knema elegans which inhibit DNA polymerase beta and cleave DNA. J Nat Prod; 68(11):1625–1628. 16. Chackalamannil S, Doller D, McQuade R, Ruperto V, 2004, Himbacine analogs as muscarinic receptor antagonists––Effects of tether and heterocyclic variations. Bioorg Med Chem Lett; 14:3967–3970. 17. Martini LH, Cereser L, Junior IZ, Jardim FM, Vendite DA, Frizzo ME, Yunes RA, Calixto JB, Wofchuk S, Souza DO, 2006, The sesquiterpenes polygodial and drimanial in vitro affect glutamatergic transport in rat brain. Neurochem Res; 31(3):431–438. 18. Chou SC, Su CR, Ku YC, Wu TS, 2009, The constituents and their bioactivities of Houttuynia cordata. Chem Pharm Bull (Tokyo); 57(11):1227–1230. 19. Hayashi K, Kamiya M, Hayashi T, 1995, Virucidal effects of the steam distillate from Houttuynia cordata and its components on HSV-1, influenza virus, and HIV. Planta Med; 61(3):237–241. 20. Chiang LC, Chang JS, Chen CC, Ng LT, Lin CC, 2003, Antiherpes simplex virus activity of Bidens pilosa and Houttuynia cordata. Am J Chin Med; 31(3):355–362. 21. Choi HJ, Song JH, Park KS, Kwon DH, 2009, Inhibitory effects of quercetin 3-rhamnoside on influenza A virus replication. Eur J Pharm Sci; 37(3–4):329–333. 22. Tang YJ, Yang JS, Lin CF, Shyu WC, Tsuzuki M, Lu CC, Chen YF, Lai KC, 2009, Houttuynia cordata Thunb extract induces apoptosis through mitochondrial-dependent pathway in HT-29 human colon ­adenocarcinoma cells. Oncol Rep; 22(5):1051–1056. 23. Kim SK, Ryu SY, No J, Choi SU, Kim YS, 2001, Cytotoxic alkaloids from Houttuynia cordata. Arch Pharm Res; 24(6):518–521. 24. Lu HM, Liang YZ, Yi LZ, Wu XJ, 2006, Anti-inflammatory effect of Houttuynia cordata injection. J Ethnopharmacol; 104(1–2):245–249. 25. Toda S, 2005, Antioxidative effects of polyphenols in leaves of Houttuynia cordata on protein fragmen­ tation by copper–hydrogen peroxide in vitro. J Med Food; 8(2):266–268. 26. Li W, Zhou P, Zhang Y, He L, 2011, Houttuynia cordata, a novel and selective COX-2 inhibitor with antiinflammatory activity. J Ethnopharmacol; 133(2):922–927.

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27. Lau KM, Lee KM, Koon CM, Cheung CS, Lau CP, Ho HM, Lee MY et al., 2008, Immunomodulatory and antiSARS activities of Houttuynia cordata. J Ethnopharmacol; 118(1):79–85. 28. Kim GS, Kim DH, Lim JJ, Lee JJ, Han DY, Lee WM, Jung WC et al., 2008, Biological and antibacterial activities of the natural herb Houttuynia cordata extract against the intracellular bacterial pathogen salmonella within RAW 264.7 macrophage. Biol Pharm Bull; 31(11):2012–2017. 29. Sung SH, Lee EJ, Cho JH, Kim HS, Kim YC, 2000, Sauchinone, a lignan from Saururus chinensis, attenuates CCl4-induced toxicity in primary cultures of rat hepatocytes. Biol Pharm Bull; 23(5):666–668. 30. Jung JY, Lee KY, Lee MY, Jung D, Cho ES, Son HY, 2011, Antioxidant and antiasthmatic effects of saucerneol D in a mouse model of airway inflammation. Int Immunopharmacol; 11(6):698–705. 31. Choi MS, Kim EC, Lee HS, Kim SK, Choi HM, Park JH, Han JB et al., 2008, Inhibitory effects of Saururus chinensis (LOUR.) BAILL on the development of atopic dermatitis-like skin lesions in NC/Nga rodent. Biol Pharm Bull; 31(1):51–56. 32. Song H, Kim YC, Moon A, 2003, Sauchinone, a lignan from Saururus chinensis, inhibits staurosporineinduced apoptosis in C6 rat glioma cells. Biol Pharm Bull; 26(10):1428–1430. 33. Seo BR, Lee KW, Ha J, Park HJ, Choi JW, Lee KT, 2004, Saucernetin-7 isolated from Saururus chinensis inhibits proliferation of human promyelocytic HL-60 leukemia cells via G0/G1 phase arrest and induction of differentiation. Carcinogenesis; 25(8):1387–1394. 34. Lee YK, Seo CS, Lee CS, Lee KS, Kang SJ, Jahng Y, Chang HW, Son JK, 2009, Inhibition of DNA topoisomerases I and II and cytotoxicity by lignans from Saururus chinensis. Arch Pharm Res; 32(10): 1409–1415. 35. García-Estrada C, Prada CF, Fernández-Rubio C, Rojo-Vázquez F, Balaña-Fouce R, 2010, DNA topoisomerases in apicomplexan parasites: Promising targets for drug discovery. Proc Biol Sci; 277(1689):1777–1787. 36. Hahm JC, Lee IK, Kang WK, Kim SU, Ahn YJ, 2005, Cytotoxicity of neolignans identified in Saururus chinensis towards human cancer cells. Planta Med; 71(5):464–469. 37. Song SY, Lee I, Park C, Lee H, Hahm JC, Kang WK, 2005, Neolignans from Saururus chinensis inhibit PC-3 prostate cancer cell growth via apoptosis and senescence-like mechanisms. Int J Mol Med; 16(4):517–523. 38. Park SY, Lee SH, Choi WH, Koh EM, Seo JH, Ryu SY, Kim YS, Kwon DY, Koh WS, 2007, Immunosuppressive lignans isolated from Saururus chinensis. Planta Med; 73(7):674–678. 39. Lee HD, Lee WH, Roh E, Seo CS, Son JK, Lee SH, Hwang BY, Jung SH, Han SB, Kim Y, 2011, Manassantin A inhibits cAMP-induced melanin production by down-regulating the gene expressions of MITF and tyrosinase in melanocytes. Exp Dermatol; 20(9):761–763. 40. Lee WS, Baek YI, Kim JR, Cho KH, Sok DE, Jeong TS, 2004, Antioxidant activities of a new lignan and a neolignan from Saururus chinensis. Bioorg Med Chem Lett; 14(22):5623–5628. 41. Kim SR, Sung SH, Kang SY, Koo KA, Kim SH, Ma CJ, Lee HS, Park MJ, Kim YC, 2004, Aristolactam BII of Saururus chinensis attenuates glutamate-induced neurotoxicity in rat cortical cultures probably by inhibiting nitric oxide production. Planta Med; 70(5):391–396. 42. Chebib M, Duke RK, Duke CC, Connor M, Mewett KN, Johnston GAR, 2003, Convulsant actions of calycanthine. Toxicol Appl Pharmacol; 190(1):58–64. 43. Zhang JW, Gao JM, Xu T, Zhang XC, Ma YT, Jarussophon S, Konishi Y, 2009, Antifungal activity of alkaloids from the seeds of Chimonanthus praecox. Chem Biodivers; 6(6):838–845. 44. Verotta L, Orsini F, Sbacchi M, Scheildler MA, Amador TA, Elisabetsky E, 2002, Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids. Bioorg Med Chem; 10(7):2133–2142. 45. Gu JQ, Park EJ, Totura S, Riswan S, Fong HH, Pezzuto JM, Kinghorn AD, 2002, Constituents of the twigs of Hernandia ovigera that inhibit the transformation of JB6 murine epidermal cells. J Nat Prod; 65(7):1065–1068. 46. Chen IS, Chen JJ, Duh CY, Tsai IL, 1997, Cytotoxic lignans from formosan Hernandia nymphaeifolia. Phytochem; 45(5):991–996. 47. Jang DS, Cuendet M, Su BN, Totura S, Riswan S, Fong HH, Pezzuto JM, Kinghorn AD, 2004, Constituents of the seeds of Hernandia ovigera with inhibitory activity against cyclooxygenase-2. Planta Med; 70(10):893–896. 48. Backhouse N, Delporte C, Givernau M, Cassels BK, Valenzuela A, Speisky H, 1994, Anti-inflammatory and antipyretic effects of boldine. Agents Actions; 42(3–4):114–117. 49. Ci X, Ren R, Xu K, Li H, Yu Q, Song Y, Wang D, Li R, Deng X, 2010, Schisantherin A exhibits anti-inflammatory properties by down-regulating NF-kappaB and MAPK signaling pathways in ­lipopolysaccharide-treated RAW 264.7 cells. Inflammation; 33(2):126–136.

Superorder Magnolianae Takht., 1967

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50. Tsai IL, Liou YF, Lu ST, 1989, Screening of isoquinoline alkaloids and their derivatives for antibacterial and antifungal activities. Gao Xiong Yi Xue Kexue Za Zhi; 5(3):132–145. 51. Chen KS, Wu YC, Teng CM, Ko FN, Wu TS, 1997, Bioactive alkaloids from Illigera luzonensis. J Nat Prod; 60(6):645–647. 52. Guh JH, Ko FN, Yu SM, Wu YC, Teng CM, 1995, Pharmacological evaluation of N-methyl-actinodaphnine, a new vascular alpha-adrenoceptor antagonist, isolated from Illigera luzonensis. Eur J Pharm; 279(1):33–41. 53. Willems E, Heiligers J, Vries PD, Kapoor K, Tom B, Villalón C, Saxena P, 2001, Alpha1-adrenoceptor subtypes mediating vasoconstriction in the carotid circulation of anaesthetized pigs: Possible avenues for antimigraine drug development. Cephalgia; 21(2):110–119. 54. Chen JJ, Hung HC, Sung PJ, Chen IS, Kuo WL, 2011, Aporphine alkaloids and cytotoxic lignans from the roots of Illigera luzonensis. Phytochem; 72(6):523–532.

3

Superorder Lilianae Takht., 1967*

3.1  COMMELINIDS Members of the Commelinids contain a broad array of phenolic substances (stilbenes, anthraquinones, phenanthrenes, flavonoids, diarylheptanoids, and coumarins) and some diterpenes of compelling pharmacological interest. One could reasonably contemplate the possibility of discovering cytotoxic, antibacterial, antifungal, and anti-inflammatory phenolic substances of pharmacological interest from the Commelinids. Cytotoxic: Myristoleic acid isolated from Serenoa repens (W. Bartram) Small (order Arecales, family Arecaceae) induced apoptosis in human prostate adenocarcinoma (LNCaP) cells cultured in vitro.1 A 1,4-naphthoquinone isolated from the inflorescence of Paepalanthus latipes Silveira (order Poales, family Eriocaulaceae) abrogated the survival of McCoy cells cultured in vitro, with a cytotoxic index of 35.8 μg/mL.2 Antibacterial, antifungal: Dracorhodin and dracorubin isolated from the resin of Daemonorops draco (Willd.) Blume (order Arecales, family Arecaceae) inhibited the growth of Gram-negative Staphylococcus aureus, Gram-negative Klebsiella pneumoniae, Mycobacterium smegmafis, and Candida albicans cultured in vitro.3 Emodin and protocatechuic acid isolated from Eriocaulon buergerianum Körn. (order Poales, family Eriocaulaceae) displayed antibacterial effects against Gram-negative Staphylococcus aureus with a minimum inhibitory dose of 32 μg/mL.4 An anthraquinone isolated from the flowers of Xyris pilosa Kunth (order Poales, family Xyridaceae) abrogated the survival of the fungi Fusarium oxysporum cultured in vitro.5 A dihydroisocoumarin isolated from the aerial part of Xyris pterygoblephara Steud. (order Poales, family Xyridaceae) exhibited antifungal properties against the dermatophyte fungi Epidermophyton floccosum, Trichophyton mentagrophytes, and Trichophyton rubrum as potently as amphotericin B.6 Anti-inflammatory: Series of phenanthrene derivatives including juncutol, juncusol, and dehydrojuncusol isolated from Juncus acutus L. (order Poales, family Juncaceae) displayed selective inhibition of inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated murine macrophages (RAW264.7) cultured in vitro.7 The coumarin umbelliferone isolated from Typha domingensis Pers. (order Poales, family Thyphaceae), given at doses 90 mg/kg, protected rodents in the ovalbumin aerosol experiment.8 Cosmetology: The flavonoid isopanduratin A isolated from Kaempferia pandurata Roxb. (order Zingiberales, family Zingiberaceae) inhibited the enzymatic activity of tyrosinase with an IC50 value of 10.5 μM.9 Trans- and cis-geranic acids isolated from Cymbopogon citratus (DC.) Stapf (order Poales, family Poaceae) inhibited the enzymatic activity of tyrosinase with IC50 values of 0.1 and 2.3 mM, respectively.10 *

The superorders Lilianae (Monocots), comprising 11 orders of flowering plants, and Magnolianae share an ancestor. Members of the Lilianae are classified into two major groups: the Commelinids and the non-Commelinids.

23

24

Medicinal Plants of China, Korea, and Japan

The Commelinids comprise the orders Dasypogonales, Arecales, Poales, Zingiberales, and Commelinales.

3.1.1  Order Commelinales Mirb. ex Bercht. & J. Presl, 1820 The order Commelinales comprises five families of flowering plants of which the Pontederiaceae is discussed here. 3.1.1.1  Family Pontederiaceae Kunth, 1816, nom. cons., the Water-Hyacinth Family The family Pontederiaceae consists of 9 genera and 30 species of aquatic plants widespread in tropical and subtropical regions. The leaves are arranged in a basal rosette or distributed along the stems. The blade shows parallel nervations. The inflorescence is a raceme, a spike, or a panicle. The perianth consists of 2 whorls of 3 tepals that are connate at the base. The androecium includes 2 whorls of 3 stamens. The filaments are adnate to the perianth. The anthers are tetrasporangiate and dithecal. The gynoecium consists of 3 carpels united to form a compound, superior, trilocular ovary with axile placentation. The fruits are loculicidal capsules enclosing numerous tiny seeds. The in vitro pharmacological study of this family is apparently left undone despite the presence of phenylphenalenone derivatives. Eichhornia crassipes (Mart.) Solms is the first plant discussed in this section. 3.1.1.1.1  Eichhornia crassipes (Mart.) Solms [After Johann Albrecht Friedrich Eichhorn of Prussia (1779–1856), and from Latin crassipes = with a thick stalk] History: This plant was first formally described in Nova Genera et Species Plantarum Brasiliensium by Carl Friedrich Philipp von Martius in 1823. Martius (1794–1868) was a German botanist. Common names: Water hyacinth, feng yan lan (Chinese), hotei aoi (Japanese), bu re ok jam (Korean). Basionym: Pontederia crassipes Mart. Synonyms: Eichhornia speciosa Kunth, Heteranthera formosa Miq., Piaropus crassipes (Mart.) Raf., Piaropus mesomelas Raf., Pontederia azurea Sw., Pontederia crassipes Mart., Pontederia crassipes Roem. & Schult., Pontederia elongata Balf. Habitat: This elegant, pantropical, aquatic, perennial, free-floating, and invasive weed is found in South America. Diagnosis: The roots of Eichhornia crassipes (Mart.) Solms are fibrous. The leaves are floating or immersed, thick, fleshy, somewhat spongy, smooth, and glossy. The petiole is swollen at the base and 3.5–35 cm long. The blade is orbicular, glossy, fleshy, and 2.5 cm × 3.5 cm to 10 cm × 9.5 cm. The inflorescence is a spike with 4–15 flowers. The spathes are obovate and 4–10 cm long. The flowers open after sunrise and wilt by night. The perianth is light blue and develops 6 lobes that are obovate and 1.5–3.5 cm long. The anthers are 0.2 cm long. The style is trilobed. The fruits contain 11–15-winged seeds that are 0.2 cm long (Figures 3.1 and 3.2). Medicinal uses: In Indonesia, this plant is used as vegetable. In Malaysia, the flowers are used to treat skin infection. Constituents: Eichhornia crassipes (Mart.) Solms contains phenylphenalenones including 8-phenylphenalenone and dimeric phenalenes.11,12 The flowers contain flavonoid glycosides.13

Superorder Lilianae Takht., 1967

25

FIGURE 3.1  Eichhornia crassipes (Mart.) Solms. (From Coll.: L.G. Saw. Forest Research Institute of Malaysia. Date: August 26, 2006.)

FIGURE 3.2  (See color insert.) Eichhornia crassipes (Mart.) Solms.

26

Medicinal Plants of China, Korea, and Japan

Pharmacology: The antiseptic property is confirmed as an extract of the plant abrogated the survival of a broad spectrum of bacteria cultured in vitro14 (on probable account of phenylphenalenone). O

OH O

OH

O N

R

F R1

HO 8-Phenylphenalenone

Fluoroquinolone

Bioresource: In vitro pharmacological study of phenylphenalenones for its effect on bacterial infection. The next plant discussed in this section is Monochoria hastata (L.) Solms. 3.1.1.1.2  Monochoria hastata (L.) Solms [From Greek mono = one, and choria = on its own, and from Latin hastata = spear-shaped with the basal lobes facing outward] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Arrowleaf false pickerel weed, arrowleaf Monochoria, chacha ayer, kankon ayer (Malay), jian ye yu jiu hua (Chinese). Basionym: Pontederia hastata L. Synonyms: Monochoria dilatata (Buch.-Ham.) Kunth, Monochoria hastifolia C. Presl, Monochoria sagittata (Roxb.) Kunth, Pontederia dilatata Buch.-Ham., Pontederia sagittata Roxb. Habitat: This perennial aquatic herb grows in pools, rice fields, and ditches and is found in China, Bhutan, Cambodia, India, Indonesia, Malaysia, Burma, Nepal, Sri Lanka, and Vietnam. Diagnosis: The rhizome of Monochoria hastata (L.) Solms is short. The leaves are 30–60 cm long. The blade is fleshy, hastate, broad, and 5 cm × 5 cm to 15 cm × 15 cm. The flowers are crowded on a short 6-cm-long raceme included in the leaf sheath. The pedicels are 1.5–6.5 cm long. The petals are purplish, 1.5 cm long, and present green keels. The capsules are globose and 1.5 cm in diameter (Figure 3.3). Medicinal uses: In Indonesia, the rhizome is pounded with charcoal and the resulting mixture is applied to itches. In the Philippines, the fresh leaves are applied to boils. Pharmacology: Apparently unknown. The plant may contain some phenylphenalenones such as monolaterol that has been isolated from Monochoria elata Ridl.15 One might be curious to find antibacterial phenylphenalenones from Monochoria hastata (L.) Solms. Bioresource: Antibacterial phenylphelanones: Phytochemical study and in vitro pharmacological study of monolaterol for its effect on cancer.

27

Superorder Lilianae Takht., 1967

FIGURE 3.3  Monochoria hastata (L.) Solms. (From Coll.: C. Curtis. Loc.: Malay Peninsula, Pulau Penang. Gardens 19. Date: October 1939.) H3C

OH HO

N

CH3

O O

N

O

H

O Monolaterol

CH3

Amplizone

The next plant discussed in this section is Monochoria vaginalis (Burm. f.) C. Presl. 3.1.1.1.3  Monochoria vaginalis (Burm. f.) C. Presl [From Greek mono = one, and choria = on its own, and from Latin vaginalis = sheathed] History: This plant was first formally described in Flora indica: cui Accedit Series Zoophy­ torum Indicorum nec non Prodromus Florae Capensis by Nicolaas Burman in 1768. Burman (1734–1793) was professor of botany at Amsterdam. Common names: Heart shape false pickerel weed, ya she cao (Chinese), ko nagi (Japanese), mul dal gae bi (Korean). Basionym: Pontederia vaginalis Burm. f.

28

Medicinal Plants of China, Korea, and Japan

Synonyms: Monochoria vaginalis var. pauciflora (Bl.) Merr., Pontederia plantaginea (Roxb.) Kunth. Habitat: This aquatic herb grows in rice fields, ditches, ponds, and swamps and is found in China, Bhutan, Cambodia, India, Indonesia, Japan, Korea, Laos, Malaysia, Burma, Nepal, Pakistan, the Philippines, Russia, Sri Lanka, Thailand, Vietnam, Africa, and Australia. Diagnosis: The stems of Monochoria vaginalis (Burm. f.) C. Presl are erect and fleshy. The radical leaves have a broad sheath. The petiole is 3–50 cm long. The blade is narrowly cordate, 2 cm × 0.5 cm to 20 cm × 10 cm, and acute at the apex. The flowering stems are 10–35 cm long. The inflorescence has up to 12 flowers. The peduncle is 1–3 cm long. The perianth comprises 6 tepals that are purplish, ovate, and 1.5 cm long. The anthers are 0.4 cm long. The capsules are ovoid and 1 cm long. The seeds are elliptical and minute (Figure 3.4). Medicinal uses: In Burma, this plant is used to treat indigestion and asthma and to assuage toothache. In China, the flowers are eaten. In Taiwan, this plant is used to treat cholera and to mitigate stomachache. In Malaysia, this plant is used at parturition. In Indonesia, this plant is used to cure stomach and liver illnesses, toothache, asthma, and fever. Constituents: This plant contains stigmasterol 3-O-beta-d-glucopyranoside that is antioxidant.16 Pharmacology: Insufficiently explored. The plant probably stores some phenylphenalenones with antibacterial activity against Gram-negative Vibrio cholerae. Bioresource: Antibacterial phenylphelanones: Phytochemical study and in vitro pharmacological study of phenylphenalenone for its effect on bacterial infection. Phenolics of pharmacological interest abound in the next clade: the order Zingiberales.

FIGURE 3.4  Monochoria vaginalis (Burm. f.) C. Presl. (From Coll. N. Ummul, R. Kiew, and H. Kueh. Flora of Malaya. Forest Research Institute Malaysia. Kepong, Malaysia. No.56913. Loc.: Malaysia, Pahang, Pekan, Nenasi Road, Kampung Meranti, Jalan Nenasi, secondary peat swamp, near riverine, or ponds, 3°11.15′N–103°26.23′E. Alt.: 8 m. Date: March 29, 2007.)

Superorder Lilianae Takht., 1967

29

3.1.2  Order Zingiberales Griseb., 1854 The order Zingiberales consists of eight families of which the Zingiberaceae and the Cannaceae are discussed here. 3.1.2.1  Family Cannaceae Juss., 1789, nom. cons., the Canna Family The family Cannaceae consists of the single genus Canna L. that comprises about 50 species of ginger-like herbs native to the tropical and subtropical part of the New World. Cannaceae are erect and develop from a tuberous starchy rhizome. The leaves are large, simple, and spirally arranged. The blade presents a prominent midrib and numerous lateral nerves. The inflorescence is a terminal cyme. The flowers are showy, perfect, epigynous, and irregular. The calyx comprises 3 sepals that are green or purplish, free, and spirally arranged. The corolla comprises 3 petals, one smaller than the others. The androecium consists of 1 stamen. The gynoecium consists of 3 carpels united to form a compound, is inferior, and has a trilocular ovary. The fruits are warty capsules. The commonly cultivated garden cannas are mostly of hybrid origin, with Canna indica L. as a primary parent. Canna indica L. is examined in this section. 3.1.1.2.1  Canna indica L. [From Latin canna = tube, and indica = from India] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Indian shot plant, mei ren jiao (Chinese), choukuyou kana (Japanese). Synonyms: Canna aurantiaca Roscoe, Canna bidentata Bertol., Canna carnea Roscoe, Canna cearensis Huber, Canna chinensis Willd., Canna cinnabarina Bouché, Canna coccinea Mill., Canna coccinea Roscoe, Canna coccinea var. bicolor Kraenzl., Canna coccinea W.T. Aiton, Canna compacta Roscoe, Canna concinna Bouche, Canna discolor Lindl., Canna edulis Ker Gawl., Canna exigua Bouché, Canna flavescens Link, Canna formosa Bouché, Canna heliconiifolia Bouché, Canna heliconiifolia var. xalapensis Kraenzl., Canna humilis Bouché, Canna indica var. coccinea Willd., Canna indica var. edwardsii Regel, Canna indica var. flava (Roscoe) Roscoe ex Baker, Canna indica var. limbata Petersen, Canna indica var. nepalensis (D. Dietr.) Baker, Canna indica var. orientalis Roscoe ex Baker, Canna indica var. rubra Aiton, Canna lagunensis Lindl., Canna lambertii Lindl., Canna lanuginosa Roscoe, Canna limbata Roscoe, Canna lutea Baker, Canna lutea Mill., Canna lutea var. aurantiaca Regel, Canna Maxima Lodd. ex Roscoe, Canna nepalensis D. Dietr., Canna occidentalis Roscoe, Canna orientalis Roscoe, Canna orientalis var. flava Roscoe, Canna pallida Roscoe, Canna polyclada Wawra, Canna pulchra Hassk., Canna rubra Willd., Canna sanctae-rosae Kraenzl., Canna seleriana Kraenzl., Canna sellowi Bouché, Canna speciosa Roscoe ex Sims, Canna surinamensis Bouche, Canna sylvestris Roscoe, Canna textoria Noronha, Canna variabilis Willd., Canna warszewiczii A. Dietr. Habitat: It is a magnificent perennial ginger-like herb native to tropical America and is cultivated as an ornamental plant throughout the tropical belt. Diagnosis: Canna indica L. is erect and grows from a fleshy and starchy rhizome. The sheath is glabrous. The blade is glabrous, ovate, 20 cm × 10 cm to 60 cm × 30 cm, obtuse at the base, and acuminate at the apex. The inflorescence is a raceme bearing a 1- to 2-flowered cincinni. The primary bracts are up to 15 cm long. The secondary bracts are up to 10 cm long. The floral bracts are persistent, obovate 3 cm long, and glaucous. The bracteoles are triangular and 2 cm long. The flowers are showy, red, yellow, or orange, and 5 cm long. The pedicels are 1.5 cm long. The sepals are narrowly triangular and

30

Medicinal Plants of China, Korea, and Japan

FIGURE 3.5  (See color insert.) Canna indica L.

0.9 cm × 0.2 cm to 1.5 cm × 0.5 cm. The corolla is 6.5 cm long. The corolla tube is 1.5 cm long. The corolla lobes are lanceolate and 3.5 cm × 0.5 cm to 5 cm × 0.7 cm. The androecium includes 3–4 staminodes that are narrowly obovate and 4.5–7.5 cm long. The fruits are capsular, elliptical, and 1.5 cm × 1 cm to 3 cm × 2 cm. The seeds are black, globose, and 0.5 cm in diameter (Figure 3.5). Medicinal uses: In China, the rhizomes are boiled in water and the resulting liquid is drunk to treat gonorrhea, probably because of the red color of the flowers. In Cambodia, Laos, and Vietnam, the starch from the rhizomes is applied to swellings and insect bites. The rhizomes are boiled in water and the resulting liquid is drunk to treat yaws. In the Philippines, a decoction of rhizomes is consumed to excite the discharge of urine and to check nose bleeding. Pharmacology: Extracts of Canna indica L. exhibited dramatic central and peripheral analgesic activities in the hot plate and acetic acid-induced abdominal writhing experiments, as well as an anthelminthic property against Pheritima posthuma.17 Besides, an extract of rhizomes inhibited the enzymatic activity of the human immunodeficiency virus reverse transcriptase.18 Finally, an extract of seeds showed a remarkable antioxidant effect in the 2,2-diphenyl-1-picrylhydrazyl experiment.19 One might be curious to find antibacterial agents against Treponema pertenue and other spirochaetes from the rhizomes of this plant. Bioresource: Anti-human immunodeficiency virus agent(s). Several antioxidant agents have been isolated from the next clade: the family Zingiberaceae. 3.1.2.2  Family Zingiberaceae Martinov, 1820, nom. cons., the Ginger Family The family Zingiberaceae consists of about 45 genera and 700 species of gingers native to Southeast Asia. The Zingiberaceae are perennial, rhizomatous, and aromatic herbs that contain flavonoids, arylheptanoids, and diterpenes of pharmacological interest. The leaves are simple. The blade

31

Superorder Lilianae Takht., 1967

p­ resents a prominent midrib and numerous lateral nerves. The inflorescence is a cyme. The flowers are perfect, epigynous, and zygomorphic. The calyx consists of 3 sepals that are greenish and united below to form a tube. The corolla is tubular with 3 linear or oblong lobes. The lip is broad, entire, or trilobed. The androecium is made of 1 fertile stamen that is tetrasporangiate and dithecal. The gynoecium consists of 3 carpels united into a compound, inferior ovary that is trilocular. The stigma is papillate and protrudes beyond the anthers. The fruits are capsular. The seeds are numerous, aromatic, arillate, and with a floury albumen. Several members of Zingiberaceae are used as a spice, as a source of starch, or as pharmaceutical products. Cardamom fruit (British Pharmacopoeia, 1963) consists of the dried seeds of Elettaria cardamomum var. minuscula Burkill. It has carminative properties. Amomum (Indian Pharmaceutical Codex, 1955) consists of the dried seeds of Amomum aromaticum Roxb. (Bengal Cardamom) or Amomum subulatum Roxb. (Nepal or Greater Cardamom). It is used in India as a substitute for cardamom. O

OH

HO

OH OCH3

OCH3 Curcumin

O

HO

H3CO

H (CH2)n

CH3

HO Gingerols CH3

O H3C

CH3 Cineole O

H3CO

CH3

HO [6]-Shogaol

East Indian arrowroot starch is made from the rhizomes of several species of Curcuma L. Ginger (British Pharmacopoeia, 1963) consists of the scraped and dried rhizomes of Zingiber officinale Roscoe, commercially known as unbleached Jamaica ginger. Ginger has carminative properties and

32

Medicinal Plants of China, Korea, and Japan

is sometimes added to purgatives in the belief that it prevents griping. It is also used as flavoring agent in Asian dishes. Besides, ginger has received extensive attention because of its antioxidant, anti-inflammatory, and antitumor activities. Most researchers have considered the alkylphenols gingerols and shogaols as the active components of ginger.20,21 [6]-Shogaol, for instance, exhibited a potent cytotoxic activity against human lung adenocarcinoma epithelial (A549), human ovary adenocarcinoma (SK-OV-3), human skin melanoma (SK-MEL-2), and human colorectal adenocarcinoma (HCT-15) cells cultured in vitro.22 Turmeric extracted from the rhizomes of Curcuma domestica Valeton is a common ingredient of curry powder and has gained popularity as a health supplement. Turmeric (British Pharmaceutical Codex, 1949) contains the yellow pigment curcumin and has been used to treat cholecystitis. Curcumin inhibits the growth of human rhabdomyosarcoma (A204), mouse melanoma (BT16), human glioblastoma-astrocytoma, epithelial-like (U-87), human colon cancer (HT-29), human large-cell lung cancer (NCI-H460), human osteosarcoma (HOS), and human leukemic lymphoblast (CCRF-CEM) cells cultured in vitro.23–28 Curcumin is also hepatoprotective, neuroprotective, and antioxidant.29–31 Zedoary (Japanese Pharmacopoeia, 1961) consists of the rhizomes of Curcuma zedoaria (Christm.) Roscoe that has been used as an aromatic stimulant and is carminative. In fact, most medicinal Zingiberaceae are used to treat gastrointestinal ailments. The first plant described in this section is Alpinia conchigera Griff. 3.1.2.2.1  Alpinia conchigera Griff. [After Prospero Alpini (1553–1617), an Italian botanist, and from the Greek konche = a shellfish] History: This plant was first formally described in Notulae ad Plantas Asiaticas by William Griffith in 1851. Griffith (1810–1845) was a British botanist. Common names: Langkwas ranting (Malay), jie bian shan jiang (Chinese). Synonym: Languas conchigera (Griff.) Burkill. Habitat: This perennial ginger grows in the open country near villages in China, Bangladesh, Cambodia, India, Indonesia, Laos, Malaysia, Burma, Thailand, and Vietnam. The rhizome is used in Thai cooking. Diagnosis: Alpinia conchigera Griff. is a small ginger that grows to a height of 50 cm. The rhizome is aromatic. The ligule is entire, 0.5 cm long, and tomentose. The petiole is 0.5–1 cm long. The blade is lanceolate, 20 cm × 5 cm to 30 cm × 10 cm, glabrous, obtuse at the base, and acute at the apex. The panicle is 25 cm long and terminal. The bracts are 0.5 cm long. The bracteoles are funnel-shaped, 0.3 cm long, and obliquely truncate at the apex. The calyx is pale green, cupular, 0.3 cm long, and trifid at the apex. The corolla is dull pale green with a red marking at the lip. The corolla lobes are 0.7 cm long. The lateral staminodes are red, quadrate, and 0.1 cm long. The labellum is obovate, 0.5 cm long, concave, and purple at the base. The filaments are pale yellowish, 0.5 cm long, and slender. The anthers are 0.2 cm long. The ovary is pyriform and glabrous. The berries are globose, red, 1 cm in diameter, and enclose 3–5 strongly aromatic seeds (Figures 3.6 and 3.7). Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used treat fatigue, to check uterine hemorrhages, to treat bronchitis, jaundice, headache, and vertigo, and as a postpartum remedy. In Malaysia, this plant is used to treat rheumatism and arthritis, and as a postpartum remedy. The rhizomes of Alpinia conchigera Griff. are used in traditional Thai medicine to cure indigestion. Pharmacology: The anti-inflammatory property of Alpinia conchigera Griff. has been validated experimentally: an extract of the plant exhibited antinociceptive activity in the acetic acid-induced abdominal writhing, the hot plate, and the formalin experiments, and antiinflammatory activity in the carrageenan-induced paw edema experiment.32 These effect are possibly mediated by a chalcone: cardamomin.33

Superorder Lilianae Takht., 1967

33

FIGURE 3.6  Alpinia conchigera Griff. (From Coll.: L.G. Saw, A. Howard, III, and M. McLaughlin. Flora of Malaya. No. 44598. Loc.: Malaysia, Kedah, Langkawi, Gunung Raya, Lebuk Semilang, primary lowland dipterocarp forest, 6°20′N–99°50′E. Alt.: 100 m. Date: May 6, 1996.)

FIGURE 3.7  (See color insert.) Alpinia conchigera Griff.

34

Medicinal Plants of China, Korea, and Japan

HO

OCH3

OH

O

Cardamomin

CH2

O H3C

OH

O

O Chavicol acetate

H3C

N H Acetaminophen

Other anti-inflammatory agents obtained from Alpinia conchigera Griff. are chavicol acetate and 1′S-1′-acetoxyeugenol acetate.34 The rhizomes contain an essential oil principally consisting of cineole and beta-bisabolene that showed moderate levels of antifungal and antibacterial activity in vitro.35 Besides, the rhizomes contain series of diaryheptanoids as well as flavones that probably play a role in some of the medicinal uses listed above.34 An extract of the rhizomes has been shown to abrogate the survival of a broad array of micro-organisms.35 Note that 1′S-1′-acetoxyeugenol acetate enhanced the apoptotic effects of paclitaxel in human breast adenocarcinoma (MCF-7) cells through nuclear factor-kappa B inactivation.36 Bioresource: In vitro pharmacological study of 1′S-1′-acetoxyeugenol acetate for its effect on cancer. The next plant discussed in this section is Alpinia elegans (Presl) K. Schum. 3.1.2.2.2  Alpinia elegans (Presl) K. Schum. [After Prospero Alpini (1553–1617), an Italian botanist, and from Latin elegans = elegant] History: This plant was first formally described in Reliquiae Haenkeanae by Karel Boriwog Presl in 1827. Presl (1794–1852) was a Czechoslovakian botanist. Common name: Tagbak (the Philippines). Habitat: This stout perennial ginger is found solely in the Philippines. Diagnosis: Alpinia elegans (Presl) K. Schum. grows to a height of 3 m from a stout rhizome. The stems are swollen at the base and leafy throughout. The leaves are leathery, spreading, lanceolate, 25 cm × 5 cm to 60 cm × 20 cm, and pointed at the apex. The petiole is stout and short. The inflorescence is 30 cm long. The calyx is 4 cm long. The corolla is pale strawcolored and 6.5 cm long. The corolla tube is cylindrical. The upper corolla lobe is 4 cm long, concave, and white. The lip is as long as the corolla lobes and spreading. The capsules are elliptical, woody, 4 cm long, split into 3 valves, and are crowned by the persistent calyx. Medicinal uses: In the Philippines, this plant is used externally to treat paralysis and is ­consumed to treat hemoptysis and urticaria, and to mitigate headache.

Superorder Lilianae Takht., 1967

35

Pharmacology: Apparently unknown. One could infer that the first medicinal property mentioned above could be owed to an antiviral effect against poliovirus. Note that an extract of Curcuma longa L. inhibited the replication of the hepatitis B virus cultured in vitro.37 Besides, arylheptanoids isolated from Alpinia officinarum Hance abrogated the survival of the influenza virus (H1N1) cultured in vitro.38 Flavones isolated from Kaempferia parviflora Wall. ex Baker (order Zingiberales, family Zingiberaceae) inhibited the enzymatic activity of human immunodeficiency virus protease with IC50 values of 19 μM.39 In addition, acetoxychavicol acetate isolated from the rhizomes of Alpinia galanga (L.) Willd., abrogated the survival of the human immunodeficiency virus ­cultured in vitro.40 Bioresource: Pharmacological study of acetoxychavicol acetate for its effect on human immunodeficiency virus infection. Alpinia galanga (L.) Willd. is discussed next. 3.1.2.2.3  Alpinia galanga (L.) Willd. [After Prospero Alpini (1553–1617), an Italian botanist, and from Chinese liang-kiang = mild ginger] History: This plant was first formally described in Species Plantarum, Editio Secunda by Carl Linnaeus in 1762. Linnaeus (1707–1778) was a Swedish botanist. Common names: Java galangal, lankuas (Malay), hong dou kou (Chinese), dai koryokyo (Japanese). Basionym: Maranta galanga L. Habitat: This perennial ginger grows in the forests of China, Taiwan, India, Indonesia, Malaysia, Burma, Thailand, and Vietnam. The rhizome is used in Thai, Malay, and Indonesian cooking. Diagnosis: The rhizome of Alpinia galanga (L.) Willd. is tuberous, pinkish, thick, edible, and aromatic. The pseudostems are 1.5 m tall. The ligule is orbicular and 0.5 cm long. The petiole is 0.5 cm long. The blade is oblong, 25 cm × 5 cm to 35 cm × 10 cm, hairy, attenuate at the base, and acute at the apex. The panicle is 20 cm × 30 cm. The rachis is glabrous or hairy. The branches are numerous, 2–4 cm long, and with 3 and 6 flowers. The bracts and bracteoles are persistent. The bracteoles are lanceolate and 0.8 cm long. The flowers are green-white and fragrant. The calyx is tubular, 0.6 cm long, and persistent. The corolla tube is 1 cm long. The corolla lobes are oblong and 1.5 cm long. The lateral staminodes are purple, linear, and 0.5 cm long. The labellum is white with red lines, spatulate, 2 cm long, and bifid at the apex. The filament is 1 cm long and the anther is 0.7 cm long. The capsules are red, oblong, slightly contracted at the middle, 1 cm × 0.5 cm to 1.5 cm × 0.5 cm, thin, glabrous, and enclose 3–6 seeds (Figure 3.8). Medicinal uses: The rhizome of Alpinia galanga (L.) Willd. has been incorporated in the Indian Pharmaceutical Codex (1960) under the name of Galanga Major as a remedy for flatulence, rheumatism, and catarrhal infection. In Cambodia, Laos, and Vietnam, the rhizomes are used to cure flatulence, to treat dysentery, cancer, food poisoning, and epilepsy. In Malaysia, the rhizomes are used in food, especially after childbirth, and for skin care. The seeds are used to cure flatulence, diarrhea, and vomiting. In Indonesia, the rhizomes are used to cure spleen diseases, herpes, earache, and postpartum infection. In the Philippines, the rhizomes are used to invigorate and to treat rheumatism.

36

Medicinal Plants of China, Korea, and Japan

FIGURE 3.8  Alpinia galanga (L.) Willd. (From Coll.: Sumbing and Sewan. Flora of Sabah. Herbarium of the Forest Department Sandakan. No. 125686. Loc.: Malaysia, Labang, Sepulut forest reserve, along the ­r iversides. Alt.: m.a.s.l.)

Pharmacology: The antiseptic property of Alpinia galanga (L.) Willd. has been validated experimentally: an extract of the plant abrogated the survival of Gram-positive Bacillus subtilis, Staphylococcus aureus, Streptococcus epidermis, and Gram-negative Enterobacter aerogene, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium, cultured in vitro.41 H3C O O

H CH2

O H3C

O Acetoxychavicol acetate

In addition, a crude extract of rhizomes exhibited antibacterial activity against Gram-negative Salmonella typhi, Escherichia coli, and Gram-positive vancomycin-resistant Enterococcus faecalis with inhibition of 92%, 82%, and 8%, respectively, at 400 μg/mL, on account of acetoxychavicol acetate.42 Besides, an extract of the plant abrogated the survival of the yeast Cryptococcus neoformans and  the dermatophyte fungi Microsporum gypseum cultured in vitro on probable account of ­acetoxychavicol acetate.43,44 The anticancer property of the plant has been substantiated: an extract of rhizomes abrogated the survival of cancer cells on probable account of acetoxychavicol.45 Acetoxychavicol exhibited chemopreventive effects on chemically induced tumor formation in the skin, mouth, colon, esophagus,

37

Superorder Lilianae Takht., 1967

and pancreas.46–50 Furthermore, acetoxychavicol abrogated the survival of Ehrlich’s ascites carcinoma, hepatocellular carcinoma, human colon cancer, and human myeloid leukemic cells cultured in vitro via apoptosis induction.51–54

HO

O

OH

O

Pinocembrin

Another cytotoxic agent in this plant is the flavonoid pinocembrin that abrogated the survival of several cancer cell-lines cultured in vitro via apoptosis induction.55 The anti-inflammatory property of this plant is confirmed: acetoxychavicol acetate inhibited the generation of nitric oxide by macrophages stimulated with bacterial lipopolysaccharides with an IC50 value of 2.3 μM.56 Furthermore, acetoxychavicol acetate and acetoxy eugenol acetate abrogated the secretion of beta-hexosaminidase by rat basophilic leukemia (RBL-2H3) cells stimulated with immunoglobulin E cells with IC50 values of 15 and 19 μM, respectively.57 Moreover, acetoxychavicol acetate markedly protected rodents against gastric mucosal insults.58 Another anti-inflammatory agent in this plant is p-coumaryl alcohol-gamma-O-methyl ether that attenuated intracellular reactive oxygen species and curved interferon gamma production in mouse CD4+ T lymphocyte cells stimulated with an antibody.59 OH O p-Hydroxycinnamaldehyde

The plant contains p-hydroxycinnamaldehyde that inhibited the release of hyaluronan, sulfated glycosaminoglycans, and metalloproteinase-2 primary human chondrocytes challenged with interleukin-1b.60 Extracts of rhizomes diminished the glycemia of rabbits.61 Note that 4′-hydroxycinnamaldehyde was cytotoxic against promyelocytic leukemia (HL-60) and human histiocytic lymphoma (U937) cells via apoptotic induction.62 Bioresource: In vitro pharmacological study of p-hydroxycinnamaldehyde for its effect on arthritis. The next plant discussed in this section is Alpinia globosa (Lour.) Horan. 3.1.2.2.4  Alpinia globosa (Lour.) Horan. [After Prospero Alpini (1553–1617), an Italian botanist, and from Latin globosa = globose] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. de Loureiro (1717–1791) was a Portuguese botanist. Common names: Chinese Cardamom, cui guo shan jiang (Chinese). Basionym: Amomum globosum Lour. Habitat: This perennial ginger grows wild or is cultivated in Vietnam and China. The seeds are used as a spice. Diagnosis: The pseudostems of Alpinia globosa (Lour.) Horan. are 1.5 m tall. The ligule is bifid, 2 cm long, and hairy. The petiole is 5 cm long. The blade is oblong, 45 cm × 10 cm to

38

Medicinal Plants of China, Korea, and Japan

70 cm × 15 cm, glabrous, attenuate at the base, and acute at the apex. The panicle is cylindrical, 30 cm × 5 cm, and hairy. The branches are numerous, 3.5 cm long, and apically 4–8-flowered. The bracteoles are oblong, 1 cm long, and membranaceous. The calyx is 1 cm long and trifid at the apex. The corolla lobes are linear and 1 cm long. The lateral staminodes are subulate. The labellum is white with purple stripes, oblong, 1 cm long, contracted at the base, and emarginate at the apex. The filament is 1.5 cm long. The anther is 0.5 cm long. The ovary is globose and hairy. The fruits are capsular, red, globose, and 1 cm in diameter (Figure 3.9). Medicinal uses: In China and Vietnam, this plant is used to cure flatulence. The seeds are used to induce menses and afford a remedy for malarial fever and poisoning. Pharmacology: Apparently unknown. One can reasonably assume that the carminative property mentioned above is owed to some essential oils that are commonly found in members of the genus Alpinia Roxb. The gynecological property of the plant could be owed to some phenolic estrogenic agents such as xanthorrhizol. H3C

H

HO

CH3 CH3

H3C Xanthorrhizol

Xanthorrhizol isolated from the rhizomes of Curcuma zanthorrhiza Roxb. elicited estrogenic activity in vitro.63 Besides, a diarylheptanoid isolated from Curcuma comosa Roxb. exhibited estrogenic activity both in vitro and in vivo experiments through agonistic action on estrogen receptors.64

FIGURE 3.9  Alpinia globosa (Lour.) Horan.

39

Superorder Lilianae Takht., 1967

One could infer that the antiplasmodial property of the plant involves diterpenes or flavonoids. Pimarane diterpenes isolated from Kaempferia marginata Carey ex Roscoe abrogated the survival of Plasmodium falciparum.65 Flavone derivatives isolated from Kaempferia parviflora Wall. ex Baker abrogated the survival of Plasmodium falciparum.66

HO OH CH3

HO

COOCH3

CH3 CH2

CH3

O O

H H3C



H CH3 Pimarane diterpene

H3C



CH3 3-Deoxyaulacocarpin A

The diterpene 3-deoxyaulacocarpin A isolated from the seeds of Aframomum zambesiacum (Baker) K.Schum. (order Zingiberales, family Zingiberaceae) exhibited a potent antimalarial activity against Plasmodium falciparum achieving an IC50 value of 4.97 μM.67 Bioresource: In vitro pharmacological study of 3-deoxyaulacocarpin A for its effect on malaria. The next plant discussed in this section is Alpinia japonica (Thunb.) Miq. 3.1.2.2.5  Alpinia japonica (Thunb.) Miq. [After Prospero Alpini (1553–1617), an Italian botanist, and from Latin Japonica = from Japan] History: This plant was first formally described in Systemat Vegetabilium. Editio Decima Quarta by Carl Peter Thunberg in 1784. Thunberg (1743–1828) was a Swedish botanist. Common names: Japanese Alpinia, shan jiang (Chinese), hana myoga (Japanese), kkot yang ha (Korean). Basionym: Globba japonica Thunb. Synonyms: Alpinia agiokuensis Hayata, Languas agiokuensis (Hayata) Sasaki, Languas japonica (Thunb.) Sasaki. Habitat: It is a perennial ginger found in China and Japan and is grown as an ornamental plant. Diagnosis: The pseudostems of Alpinia japonica (Thunb.) Miq. are 70 cm long. The ligule is bifid, 0.2 cm long, and hairy. The petiole is 2 cm long. The blade is elliptical, 25 cm × 5 cm to 40 cm × 7 cm, hairy, attenuate at the base, and acuminate at the apex. The raceme is 30 cm long. The rachis is densely tomentose. The involucral bracts are lanceolate, 10 cm long, and deciduous at anthesis. The bracteoles are tiny and deciduous. The flowers are paired on the rachis. The calyx is clavate, 1.2 cm long, hairy, and trifid at the apex. The corolla tube is 1 cm long, reddish, and puberulent. The corolla lobes are oblong, 1 cm long, and abaxially tomentose. The central corolla lobe is hood-like. The lateral staminodes are linear and 0.5 cm long. The labellum is white marked with red stripes, ovate, 0.5 cm wide, irregularly notched, and bifid at the apex. The stamen is 1.4 cm long. The ovary is densely tomentose. The capsules are red, globose, 1.5 cm in diameter, hairy, and present a persistent calyx at the apex. The seeds are 0.5 × 0.3 cm, polygonal, and release a camphor-like odor when crushed (Figure 3.10).

40

Medicinal Plants of China, Korea, and Japan

FIGURE 3.10  Alpinia japonica (Thunb.) Miq.

Medicinal uses: In China, the fruits are used to treat indigestion and the rhizomes provide a remedy for boils. Constituents: Alpinia japonica Miq. contains series of sesquiterpenes of which 4-alphahydroxydihydroagarofuran, alpha-agarofuran, beta-eudesmol, hanalpinol, alpiniol, alpinolide, hanamyol, and pogostol probably contribute to the antiseptic property of the rhizome.68–70 Pharmacology: One might be curious to look for antibiotic agents in the rhizome Alpinia japonica (Thunb.) Miq. H3C

HO O H3C

H

H

H H

O

H3C H3C

CH3

CH3

 

O

O

Hanalpinol

O

O O

CH3 H3C

O

H3C

CH3

CH3

O Artemisinin

Alpinolide

CH3

HO CH3 O

H3C Hanamyol

CH3

O

Superorder Lilianae Takht., 1967

41

Bioresource: Pharmacological study of hanalpinol for its effect on malaria. The next plant discussed in this section is Alpinia melanocarpa Ridl. 3.1.2.2.6  Alpinia melanocarpa (Teijsm. & Binn.) Ridl. [After Prospero Alpini (1553–1617), an Italian botanist, and from Greek melano = black, and karpos = fruit] History: This plant was first formally described in Natuurkundig Tijdschrift voor Nederlandsch-Indië by Johannes Elias Teijsmann and Simon Binnendijk in 1862. Teijsmann (1808–1882) and Binnendijk (1821–1883) were Dutch botanists. Common names: Black-fruited Alpinia, munkanang (Malay). Basionym: Hellenia melanocarpa Teijsm. & Binn. Habitat: This perennial ginger grows by the seaside in Malaysia and Borneo. Diagnosis: The pseudostems of Alpinia melanocarpa Ridl. are greenish, 1 m tall, and slender. The rhizome is stout and aromatic. The leaves are oblong, acute at the apex, asymmetrical at the base, and 18 cm × 5 cm. The panicle is 15 cm long, has short branches, and displays 3 flowers. The calyx is 1.5 cm long, white, and funnel-shaped. The corolla lobes are oblong, blunt, and white tinged with purple. The base of the lip is narrow, the limb is bilobed, and the lobes are oblong, blunt, and white. The 2 staminodes are small. The fruits are peashaped black or red capsules. The seeds are light brown and embedded in a white aril (Figure 3.11). Medicinal uses: In Malaysia, a decoction of the flowers is ingested to treat cholera. A decoction of rhizomes is ingested as a postpartum medicine. Pharmacology: The anticholera property of the plant has not been validated experimentally yet but members of the family Zingiberaceae have been shown to produce a broad range of antibacterial phenolic and terpene substances. The chalcone panduratin A isolated from Boesenbergia rotunda (L.) Mansf. exhibited dramatic antibacterial activity against staphylococcal isolates.71 [10]-Gingerol and [12]-gingerol isolated from Zingiber officinale Roscoe effectively inhibited the growth of Gram-negative oral Porphyromonas gingivalis, Porphyromonas endodontalis, and Prevotella intermedia cultured in vitro.72 Xanthorrhizol isolated from Curcuma zanthorrhiza Roxb. exhibited some levels of antibacterial activity against Gram-positive Bacillus cereus, Clostridium perfringens, Listeria monocytogenes, Staphylococcus aureus and Gram-negative Salmonella typhimurium and Vibrio parahaemolyticus cultured in vitro.73 Difurocumenonol isolated from Curcuma amada Roxb. exhibited a remarkable antibacterial activity against Gram-negative and Gram-positive bacteria.74 The diterpene miogadial isolated from Zingiber mioga (Thunb.) Rosc. exhibited some antibacterial property.75 Bioresource: In vitro pharmacological study of difurocumenonol for its effect on acne. The next plant discussed in this section, Alpinia officinarum Hance, is also used to treat cholera. 3.1.2.2.7  Alpinia officinarum Hance [After Prospero Alpini (1553–1617), an Italian botanist, and from Latin officinare = sold as an herb] History: This plant was first formally described in Journal of the Linnean Society, Botany by Henry Fletcher Hance in 1873. Hance (1827–1886) was a British diplomat.

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.11  Alpinia melanocarpa Ridl. (From Coll.: Y.P. Ching. Det: Paie I. Sarawak Forest Department. No. 37864. Loc.: Malaysia, Tg. Batu beach, Bintulu, 4th Division. Sandy soil. Alt.: a.s.l. Date: October 22, 1976; February 2, 1983.)

Common names: Lesser galangal, gao liang jiang (Chinese), raosu (Japanese), Synonyms: Languas officinarum (Hance) Farw., Languas officinarum (Hance) P.H. Hô. Habitat: This ginger is found in China, Cambodia, Laos, and Vietnam. It is cultivated in Asia for the rhizomes that are edible and medicinal. Diagnosis: The rhizome of Alpinia officinarum Hance is elongate and terete. The pseudostems are 1 m tall. The leaves are sessile. The ligule is lanceolate, entire, 2–5 cm long, and membranaceous. The blade is linear, 20 cm × 1 cm to 30 cm × 2.5 cm, and elliptical. The raceme is erect and 5–10 cm long. The rachis is tomentose. The bracteoles are tiny. The calyx is 1 cm long and trifid at the apex. The corolla lobes are oblong and 1.5 cm long. The labellum is white and 2 cm long. The filaments are 1 cm long. The anthers are 0.5 cm long. The fruits are capsular, red, globose, and 1 cm in diameter (Figure 3.12). Medicinal uses: Galanga (British Pharmaceutical Codex, 1934) consists of the rhizomes of lesser galangal and has been used as an infusion to promote digestion. In China, the rhizomes are used to promote digestion, to treat diarrhea and cholera, to assuage toothache, and to break malarial fever. In Cambodia, Laos, and Vietnam, this plant is used to cure fatigue and to mitigate toothache and headache. Pharmacology: The carminative property of Alpinia officinarum Hance is most probably owed to alpha-pinene, beta-pinene, eucalyptol, and alpha-terpineolin.76 Besides, the plant contains some arylheptanoids that displayed a dramatic cytotoxic effect against neuroblastoma cells cultured in vitro via apoptosis induction.77 Other arylheptanoids obtained from this plant abrogated the survival of the influenza virus (H1N1) cultured in vitro and inhibited platelet-activating factor receptor binding activities.38,78 The anti-inflammatory property is confirmed: an extract of Alpinia officinarum Hance abrogated the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides on probable account of arylheptanoids.79,80

43

Superorder Lilianae Takht., 1967

FIGURE 3.12  Alpinia officinarum Hance.

In addition, the plant contains series of arylheptanoids with antiemetic properties.81 Other arylheptanoids obtained from the rhizomes inhibited the enzymatic activity of 5-alpha-reductase in vitro82 and inhibited the enzymatic activity of pancreatic lipase.82,83 Another inhibitor of pancreatic lipase present in this plant is 3-methylethergalangin.84

OH HO p-Coumaryl alcohol

Alpinia officinarum Hance contains some antioxidant agents such as p-coumaryl alcohol.85 The antibacterial property of this plant is confirmed: an extract of rhizomes abrogated the survival of Gram-positive Staphylococcus aureus and Streptococcus pneumoniae cultured in vitro.86 The rhizomes contain a substantial amount of flavonoids including galangin that exhibited compelling pharmacological activities including chemopreventive properties.87

HO

O

OH OH

O Galangin

Bioresource: In vitro pharmacological study of p-coumaryl alcohol for its effect on skin ageing. The next plant discussed in this section is Amomum compactum Sol. ex Maton.

44

Medicinal Plants of China, Korea, and Japan

3.1.2.2.8  Amomum compactum Sol. ex Maton [From Greek amomon = an Indian spice used by the Romans, and from Latin compactum = growing in compact form] History: This plant was first formally described in Transactions of the Linnean Society of London by William George Maton in 1811. Maton (1774–1835) was a British physician. Common names: Chester Cardamom, round cardamom, Java amomum, zhao wa bai dou kou (Chinese). Synonym: Amomum kepulaga Sprague & Burkill. Habitat: It is a perennial ginger native to Indonesia and is cultivated in Asia for its aromatic fruits. Diagnosis: Amomum compactum Sol. ex Maton is 1.5 m tall. The leaves are sessile. The ligule is orbicular, bifid, and 0.5 cm long. The blade is elliptical, 25 cm × 5 cm to 50 cm × 10 cm, glabrous, and acute at the apex. The inflorescence is a cylindrical spike that is 5 cm × 2.5 cm. The bracts are yellow, ovate, 2.5 cm long, striate, persistent, and ciliate at the margin. The bracteoles are tubular. The calyx is 1 cm long, hairy, and trifid at the apex. The corolla is whitish. The corolla tube is 1.2 cm long. The corolla lobes are oblong and 1 cm long. The labellum is yellowish and purple, elliptical, 1.5 cm × 1 cm to 2 cm × 1.5 cm, concave, and hairy. The filament is hairy at the base. The anther is elliptical and minute. The ovary is hairy. The capsules are yellowish, 1.5 cm in diameter, slightly 9-grooved when dry, and hairy. The seeds are polyhedral and 0.5 cm in diameter (Figure 3.13). Medicinal uses: In China, this plant is used to stop vomiting, to mitigate stomachache, to break malarial fever, and to treat eye diseases and gout. In Malaysia, this plant is used to treat cough, colds, liver diseases, and rheumatism and to mitigate stomachache. In Indonesia, this plant is used to cure fatigue, to treat rheumatism, catarrhal infection, and impotence, to perfume the mouth, and to cleanse wounds. Pharmacology: The anti-inflammatory and analgesic properties of the plant have been validated: Lee and coworkers88 proved that Amomum compactum Sol. ex Maton had antiasthmatic activity in rodent. Besides, the gastroprotective property of Amomum compactum Sol. ex Maton is confirmed: an extract of Amomum xanthioides Wall. ex Baker protected rodents against HCl-

FIGURE 3.13  Amomum compactum Sol. ex Maton.

45

Superorder Lilianae Takht., 1967

induced gastric damage.89 Moreover, extracts of Amomum subulatum Roxb. inhibited the gastric damages induced by aspirin in rodents.90 The anti-inflammatory and analgesic agents involved here are yet to be identified but one can reasonably think of bornyl acetate. Bornyl acetate isolated from the essential oil of Amomum villosum Lour. displayed significant analgesic and anti-inflammatory properties in rodents.91,92 Bioresource: Anti-inflammatory and/or antiasthmatic agent(s). Bornyl acetate is present in Amomum villosum Lour., discussed next. 3.1.2.2.9  Amomum villosum Lour. [From Greek amomon = an Indian spice used by the Romans, and from Latin villosum = hairy] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Hairy amomum, sha ren (Chinese). Habitat: This perennial ginger grows wild in the wet and shady spots in the forests of China, Cambodia, India, Laos, Burma, Thailand, and Vietnam. The plant is cultivated for its edible fruits. Diagnosis: Amomum villosum Lour. grows to a height of 2.5 m. The rhizome is procumbent and covered with brown scale-like sheaths. The leaves are sessile. The ligule is orbicular and 0.5 cm long. The blade is elliptical, 25 cm × 3 cm to 35 cm × 5 cm, glabrous, and acute at the apex. The spike is elliptical. The bracts are lanceolate and 1.5 cm long. The bracteoles are tubular and 1 cm long. The calyx is white, 1.5 cm long, hairy, and trifid at the apex. The corolla tube is 2 cm long. The corolla lobes are white, obovate, and 1.5 cm × 0.5 cm to 2 cm × 0.7 cm. The labellum is whitish with purple spots, orbicular, 2 cm wide, convex, clawed at the base, and bifid at the apex. The filament is 0.5 cm long. The anther is 0.5 cm long. The ovary is white and hairy. The fruits are a purple, green, brownish capsules that are globose, 2 cm in diameter, and spiny. The capsules contain several seeds that are polygonal, edible, and strongly aromatic (Figure 3.14). Medicinal uses: In China, the seeds are used to cure indigestion, flatulence, fatigue, dysentery, and constipation, to prevent miscarriage, and to excite the discharge of urine. H3C

CH3 CH3 CH3 O O Bornyl acetate

Constituents: Quercitrin and isoquercitrin (as well as ethyl octacosate, docosyl hexylate, stigmast-4-ene-1,3-dione, beta-sitosterol, and daucosterol) have been obtained from the plant.93,94 Pharmacology: The carminative and digestive properties of Amomum villosum Lour. are most probably owed to the presence of essential oils in the rhizomes. The nootropic, diuretic, and progesteronemic properties of Amomum villosum Lour. are yet to be explored. The essential oils of this plant contains bornyl acetate that exhibited analgesic and antiinflammatory effects in rodents.91,92 Bioresource: Phytochemical study and in vitro pharmacological study of bornyl acetate for its effect on inflammation. The next plant discussed in this section is Boesenbergia rotunda (L.) Mansf.

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.14  Amomum villosum Lour.

3.1.2.2.10  Boesenbergia rotunda (L.) Mansf. [After Clara and Walter Boesenberg, in-laws of the German botanist Carl Ernst Otto Kuntze (1843– 1907), and from Latin rotunda = round] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Fingerroot, Chinese ginger, kra chai (Thai), ao chun jiang (Chinese), obangajutsu (Japanese). Basionym: Curcuma rotunda L. Synonyms: Boesenbergia pandurata (Roxb.) Schltr., Kaempferia pandurata Roxb. Habitat: This perennial ginger is found in the forests of India, Indonesia, Thailand, Malaysia, and Sri Lanka. It is cultivated for its aromatic fruits. Diagnosis: Boesenbergia rotunda (L.) Mansf. grows to a height of 50 cm. The rhizome is bright yellow, odd, very peculiarly hand-shaped, edible, and strongly aromatic. The leaves are arranged in groups of 3 or 4. The sheaths are red. The ligule is bifid and 0.5 cm long. The petiole is 7–15 cm long and channeled. The blade is ovate or orbicular, 25 cm × 7 cm to 50 cm × 10 cm, round at the base, and acute or acuminate at the apex. The inflorescence is 3–7 cm long. The bracts are lanceolate and 4–5 cm long. The flowers are aromatic. The calyx is 2 cm long and bifid at the apex. The corolla is pink. The corolla tube is 5 cm long. The corolla lobes are oblong and 2 cm long. The lateral staminodes are light pink, obovate, and 1.5 cm long. The labellum is whitish with pink stripes, 3.5 cm long, concave, and crisped. The filament is short. The connective appendage is reflexed, bifid, and 0.3 cm long (Figure 3.15). Medicinal uses: In China, Cambodia, Laos, and Vietnam, the rhizomes are used to cure flatulence, fatigue, and dysmenorrhea, and to promote the discharge of bile. In Malaysia, the rhizomes are used to break malarial fever, to cure cough and fatigue, and is given postpartum. In Indonesia, the rhizomes are used to excite the discharge of urine and to treat cough, flatulence, and gynecological inflammation.

47

Superorder Lilianae Takht., 1967

FIGURE 3.15  Boesenbergia rotunda (L.) Mansf. (From Coll.: W. Fox. Dept. of Syst. Botany, University of Aarhus (Herbarium AAU). Loc.: Malay Peninsula, Pulau Penang. Alt.: 750 feet. Date: July 1899.)

Pharmacology: The carminative property of Boesenbergia rotunda (L.) Mansf. is most probably owed to the presence of essential oils. Besides, this plant contains the cyclohexenyl chalcone derivatives hydroxypanduratin A and panduratin A that showed remarkable anti-inflammatory activity in the 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in rodents.95

H HO

OH

H OH

O

CH3 H H3C

CH3

Panduratin A

Moreover, panduratin A isolated from the rhizomes of Boesenbergia pandurata Schult. showed significant antioxidant effect in the rat brain homogenate experiment.96 4-Hydroxypanduratin A and panduratin A isolated from Boesenbergia rotunda (L.) Mansf. inhibited the enzymatic activity of dengue 2 virus NS3 protease.97 Hydroxypanduratin A isolated from Boesenbergia pandurata Schult. impeded the enzymatic diligence of human immunodeficiency virus protease achieving an IC50 value of 5.6 μM.98 Another flavonoid of pharmacological interest found in Boesenbergia rotunda (L.) Mansf. is 2,6-dihydroxy-4-methoxydihydrochalcone that significantly inhibited tumor necrosis factor-alphainduced cytotoxicity in cancer cells at 10 μM.99 Note that pandurantin A induced apopotosis in human lung adenocarcinoma epithelial (A549) cells cutured in vitro.100

48

Medicinal Plants of China, Korea, and Japan

Bioresource: In vitro pharmacological study of hydroxypanduratin A for its effect on human immunodeficiency virus infection. The next plant discussed in this section is Costus speciosus (J. König) Sm. 3.1.2.2.11  Costus speciosus (J. König) Sm. [From Latin costus = cost, and speciosus = showy] History: This plant was first formally described in Transactions of the Linnean Society of London by Johann Gerhard König in 1791. König (1728–1785) was a German botanist. Common names: Spiral ginger, tawar (Malay), bi qiao jiang (Chinese). Basionym: Banksea speciosa J. König. Synonyms: Banksia speciosa König, Costus formosanus Nakai, Costus speciosus var. hirsutus Blume, Costus speciosus var. leocalyx (K. Schum.) Nakai, Costus spicatus var. pubescens Griseb., Hellenia grandiflora Retz. Habitat: This perennial ginger grows in damp open spots in Malaysia, Cambodia, Laos, Vietnam, Thailand, Sri Lanka, the Philippines, Australia, and Indonesia. It is a common tropical ornamental plant. Diagnosis: The stems of Costus speciosus (J. König) Sm. are 2 m tall, reddish, and spiral. The leaves are shortly petiolate, 18 cm × 10 cm, hairy below, and oblong acuminate. The spike is ovate, terminal, and 15 cm long. The bracts are ovate, mucronate, red, and 2 cm long. The calyx is short and red. The corolla lobes are 6 cm long, white, showy, and often pinkish. The lip is 12 cm wide, white and yellow. The stamen is 6 cm long, hairy, and orange (Figure 3.16). Medicinal uses: In Cambodia, Laos, and Vietnam, the juice extracted from this plant is ingested to treat diarrhea. In Indonesia, this plant is used to treat eye diseases. In Laos and Malaysia, this plant is used to make a bath to break fever. In Malaysia, the flowers are used to exorcize. Constituents: Diosgenin, prosapogenin B of dioscin, diosgenone, cycloartanol, 25-en-cycloartenol, and octacosanoic acid occur in the rhizomes.101 Pharmacology: Costus speciosus (J. König) Sm. contains a methyl ester of p-coumaric acid that is antifungal.102 An extract of roots exhibited antihyperglycemic, antihyperlipemic, and antioxidative effects in alloxan-induced diabetic rodents on possible account of the sesquiterpene lactones costunolide and eremanthin.103–105 Costunolide has exhibited an impressive array of pharmacological properties, including anti-inflammatory, antifungal, and antiviral properties.106–109 H2C

CH3

CH3 CH2 CH3

O

H2C

O



O

O Costunolide



Eremanthin

Besides, costunolide elicited anticarcinogenic activity in animals.110–113 Furthermore, costunolide induced differentiation in human promyelocytic leukemia (HL-60) and exhibited cytotoxic activities against various human cancer cells cultured in vitro.114–117 In addition, costunolide was able to induce apoptosis in human promyelocytic leukemia (HL-60) and human histiocytic lymphoma (U937) cells cultured in vitro.118–122 Costunolide interacted with

Superorder Lilianae Takht., 1967

49

FIGURE 3.16  (See color insert.) Costus speciosus (J. König) Sm.

microtubule proteins and inhibited the growth of human breast adenocarcinoma (MCF-7) cells cultured in vitro.123 Costunolide inhibited the enzymatic activity of telomerase in human breast cancer cells.124 Note that costunolide attenuated the expression of tumor necrosis factor-alpha, interleukin-1, interleukin-6, inducible nitric oxide synthase, monocyte chemotactic protein 1, and cyclooxygenase-2 in activated microglia.125 Bioresource: In vitro pharmacological study of costunolide for its effect on breast cancer. The next plant discussed in this section is Curcuma aromatica Salisb. 3.1.2.2.12  Curcuma aromatica Salisb. [From Arabic kurkum = turmeric, and from Latin aromatica = fragrant] History: This plant was first formally described in The Paradisus Londinensis by Richard Anthony Salisbury in 1807. Salisbury (1761–1829) was a British botanist. Common names: Wild turmeric, yu jin (Chinese), haruukon (Japanese). Habitat: This superb perennial ginger is native to India and is cultivated in Burma, Bhutan, Nepal, and Sri Lanka for its fragrant rhizome. Diagnosis: Curcuma aromatica Salisb is 1 m tall. The rhizome is brightly yellow inside, elliptical, fleshy, edible, and strongly aromatic. The blade is elliptical, 30 cm × 10 cm to 60 cm × 20 cm, hairy, attenuate at the base, and acute at the apex. The inflorescence is a cylindrical spike that is 15 cm long. The bracts at the apex are light pink, ovate, and 5 cm long. The calyx is hairy and 1.5 cm long. The corolla tube is funnel-shaped, 2.5 cm long, and hairy at the throat. The corolla lobes are pinkish, oblong, and 1.5 cm long. The lateral staminodes are yellowish, obovate, and 1.5 cm long. The labellum is yellow, obovate, 2.5 cm long, and emarginate at apex (Figure 3.17). Medicinal uses: In China, the rhizomes are used to cure flatulence, fatigue, epilepsy, delirium, and rheumatism and to induce menses.

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Medicinal Plants of China, Korea, and Japan

Pharmacology: The essential oil of Curcuma aromatica Salisb. contains curdione, germacrone, cineole, germacrone-4,5-epoxide, beta-elemene, and linalool that probably account for the carminative property mentioned above.126 Note that this essential oil and an aqueous extract exhibited antitumor properties against esophageal cancer and hepatoma in rodents on probable account of beta-elemene that has been found to inhibit the multiplication of human and murine tumor cells in vitro and in vivo.127–131 Besides, an aqueous extract of the plant induced apoptosis and G2/M arrest in human colon carcinoma LS-174-T cells cultured in vitro.132 CH3 H2C H2C

CH2 CH3

H

H

CH3

Beta-elemene

Besides, beta-elemene has been used to treat carcinomas of the brain, liver, breast, and other tissues as well as leukemia in China.133–136 In addition, beta-elemene abrogated the survival of human lung cancer cells.135 The anti-inflammatory property of this plant is most probably owed to curcumin. Curcumin isolated from this plant protected rodents against passive cutaneous anaphylaxis triggered by immunoglobulin E.137 Curcumin might also have been involved in the anticonvulsive property of the plant as, at a dose of 100 mg/kg, it protected rodents against electroshock-induced seizures.138 Note that an extract of Curcuma aromatica Salisb. displayed some levels of estrogenic activity in vitro.139 Bioresource: In vitro pharmacological study of beta-elemene for its effect on cancer. The next plant discussed in this section is Curcuma pallida Lour.

FIGURE 3.17  Curcuma aromatica Salisb. (From Coll.: J. Skornickova. Flora of Indonesia. No. 74715. Loc.: Indonesia, Kalimantan, Timor, Tubu region. Date: May 25, 2001.)

51

Superorder Lilianae Takht., 1967

3.1.2.2.13  Curcuma pallida Lour. [From Arabic kurkum = turmeric, and from Latin pallida = pale] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Red leaf spice ginger, temu kuning (Malay), er chu (Chinese). Habitat: This ginger is found in Malaysia, the Philippines, and Indonesia. Diagnosis: The rhizome of Curcuma pallida Lour. is large, fleshy, and orange inside. The leaves are arranged in pairs, lanceolate, green with a purple central mark, and 50 × 15 cm. The inflorescence is a spike that is 50 cm tall and made of 20 bracts that are green, pinkish, showy, and lanceolate. The calyx is 0.75 cm long. The staminodes are oblong. The lip is oblong, bilobed, and yellowish and orange. The anther is spurred. Medicinal uses: In China, this plant is used to cure fatigue, to sooth inflammation, to increase the fluidity and the circulation of blood, and to alleviate painful menses. In Taiwan, this plant is used to treat heart diseases, cholera, gonorrhea, irregular menses, and snakebites. In Cambodia, Laos, and Vietnam, this plant is used to cure fatigue, to promote menses, and for food. In Malaysia, this plant is used to cure fatigue and as protection against evil spirits. In Indonesia, this plant is used postpartum. In the Philippines, this plant is used to heal wounds and ulcers. O

OH

HO

OH OCH3 Demethoxycurcumin

Pharmacology: A decoction of Curcuma pallida Lour. exhibited a mild antimutagenic activity against benzo[a]pyrene in rodents on probable account of arylheptanoids such as curcumin, demethoxycurcumin, and bisdemethoxycurcumin that abrogated the ­survival of human ovarian carcinoma cell line cultured in vitro.140,141 Besides, ­f uranodiene, germacrone, neocurdione, curcumenol, isocurcumenol, aerugidiol, ­zedoarondiol, curcumenone, curcumin, and curdione extracted from the plant protected rodents  against d-galactosamine/bacterial lipopolysaccharide-induced hepatocellular damage.142 O CH3

CH3

O

CH3 CH3

Curdione

The anti-inflammatory property of Curcuma pallida Lour. is confirmed: curdione inhibited the generation of prostaglandin E2 by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides with an IC50 value of 1.1 μM.143

52

Medicinal Plants of China, Korea, and Japan CH3

CH3

O

CH3

Furanodiene

Other anti-inflammatory sesquiterpenes extracted from the plant are furanodiene and furanodienone that inhibited 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in rodents.144 Moreover, dehydrocurdione isolated from the plant exhibited analgesic and antipyretic activities in the acetic acid-induced abdominal writhing experiment and the Baker’s yeast experiment, respectively. In addition, dehydrocurdione displayed anti-inflammatory activity in the carrageenaninduced paw edema experiment.145

H O CH3 CH3



O Curcumenol

H3C

CH3

O CH3

H3C

CH3 H3C

CH3



Dehydrocurdione

Finally, curcumenol obtained from the rhizomes elicited potent analgesic properties in several pain experiments.146 Extracts of the plant showed antibacterial and antifungal properties in vitro, the later property probably owed to ethyl p-methoxycinnamate.147,148 Bioresource: In vitro pharmacological study of curdione for its effect on inflammation. The next plant discussed in this section is Curcuma zanthorrhiza Roxb. 3.1.2.2.14  Curcuma zanthorrhiza Roxb. [From Arabic kurkum = turmeric, and from Greek xantho = yellow, and rhiza = root] History: This plant was first formally described in Flora Indica; or Descriptions of Indian Plants by William Roxburgh in 1820. Roxburgh (1751–1815) was a Scottish botanist. Common names: False turmeric, temu lawak, temoe lawak (Malay), yin ni e zhu (Chinese). Habitat: It is a perennial ginger found by the riversides of Indonesia, Malaysia, and Thailand. It is cultivated for food. Diagnosis: Curcuma zanthorrhiza Roxb. grows to a height of 2 m. The rhizome is deep orange inside and edible. The petiole is 10 cm long. The blade is green with a purple midrib, oblong, and 40 cm × 15 cm to 80 cm × 20 cm. The inflorescence is a spike that is 25 cm × 10 cm. The bracts are reddish violet. The calyx is whitish, 1.5 cm long, hairy, and trifid at the apex. The corolla tube is 3.5 cm long. The corolla lobes are pale purple, ovate, and 1.5 cm long. The lateral staminodes are yellowish, tinged with purple, and oblong. The labellum is yellowish, square, and 2 cm wide. The anther is 0.5 cm long.

53

Superorder Lilianae Takht., 1967

Medicinal uses: In Malaysia, the rhizomes are used to treat abdominal and liver illnesses including jaundice. The rhizomes are also a remedy for malarial fever, constipation, lack of milk, dysentery, hemorrhoids, putrefied wounds, and allergies. O CH3

CH3 CH3

CH3 Germacrone

Pharmacology: Curcuma zanthorrhiza Roxb. is anti-inflammatory: an extract of the plant inhibited the mouse ear edema induced by 12-O-tetradecanolyphorbol-13-acetate149 on probable account of an arylheptanoid that displayed a remarkable anti-inflammatory activity in the ethyl phenylpropiolate-induced ear edema experiment.150 Besides, arylheptanoids extracted from the plant elicited remarkable anti-inflammatory activities in the carrageenan-induced paw edema experiment.151 Another anti-inflammatory and analgesic agent found in this plant is the sesquiterpene germacrone that displayed some levels of activities in the carrageenan-induced paw edema experiment and the acetic acid-induced abdominal writhing experiment.152 Curcuma zanthorrhiza Roxb. has a chemopreventive property: an extract of the plant abrogated 7,12-dimethylbenz[a]anthraceneinduced bacterial mutagenesis of Salmonella typhimurium.149 H3C

H

HO

H3C

CH3 CH3

Xanthorrhizol

Besides, this plant contains xanthorrhizol that inhibited the proliferation of human breast adenocarcinoma (MCF-7) and human colorectal carcinoma (HCT-116) cells cultured in vitro via apoptosis induction.153,154 Xanthorrhizol is also anticandidal, antioxidant, antibacterial, antifungal, and estrogenic.63,155–159 Xanthorrhizol derivatives extracted from the plant showed antibabesial activity.160 In addition, an extract of the plant displayed antiplasmodial property in vitro on probable account of xanthorrhizol.161 The hepatoprotective property of the plant has been validated.162 Bioresource: In vitro pharmacological study of xanthorrhizol for its effect on breast cancer. The next plant discussed in this section is Globba aurantiaca Miq. 3.1.2.2.15  Globba aurantiaca Miq. [From Indonesian galoba and from Latin aurantiaca = orange-yellow] History: This plant was first formally described in Flora van Nederlandsch Indie, Eerste Bijvoegsel by Friedrich Anton Wilhelm Miquel in 1861. Miquel (1811-1871) was a Dutch botanist. Common names: Pua gumbur, menderong gajah (Malay). Habitat: It is a perennial ginger found in the rainforests of Malaysia and Indonesia.

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Medicinal Plants of China, Korea, and Japan

Diagnosis: Globba aurantiaca Miq. is 50 cm tall. The blades are asymmetrical, elliptical, hairy below, 20 cm × 9 cm, and emerge from a hairy sheath. The peduncle is 25 cm long and hairy. The panicle is 10–25 cm long. The branches are 0.75 cm long. The flowers are few and orange. The bracts are oblong, hairy, and orange. The calyx is funnel-shaped and 0.75 cm long. The calyx lobes are short and blunt. The corolla tube is 1.5 cm long. The corolla lobes are large and oblong. The staminodes are short. The lip is short, broad, oblong, bilobed, and display a central brown spot. The anther spurs are triangular (Figure 3.18). Medicinal use: In Malaysia, the rhizomes are boiled in water and the liquid obtained is drunk as a postpartum remedy. Pharmacology: Apparently unknown. Quercetin 3-rutinoside, also known as rutin, has been obtained from this plant.163 Rutin displayed an impressive number of pharmacological activities including antioxidant, hepatoprotective, anti-inflammatory, and neuroprotective activities.164–167 OH OH HO

O

O OH OH

O CH3 OH

OH

O

O

O OH OH OH Rutin

FIGURE 3.18  Globba aurantiaca Miq. (From Coll.: Hamid. Flora of Malay Peninsula. Forest Department. No. 4973. Loc.: Malaysia, Kuala Lumpur. Date: November 25, 1919.)

Superorder Lilianae Takht., 1967

55

Bioresource: In vitro pharmacological study of rutin for its effect on neurodegeneration. The next plant discussed in this section is Globba pendula Roxb. 3.1.2.2.16  Globba pendula Roxb. [From Indonesian galoba and from Latin pendula = pendulous] History: This plant was first formally described in Asiatic Researches by William Roxburgh in 1810. Roxburgh (1751–1815) was a Scottish botanist. Common names: Silver comet, halia hutan (Malay). Habitat: This perennial ginger grows in the rainforests of Burma, Thailand, Malaysia, and Indonesia. Diagnosis: The pseudostems of Globba pendula Roxb. are 1 m tall. The leaves are elliptical or ovate, purplish beneath, cuspidate or caudate, glabrous, and 30 × 12 cm. The ligule is round and hairy. The sheaths are red and hairy at the margin. The inflorescence is 5 cm long and has few flowers. The flowers are orange. The calyx is funnel-shaped and develops unequal lobes. The corolla tube is 1.5 cm long. The corolla lobes are 0.75 cm long. The staminodes are oblanceolate. The lip is narrow, bilobed, and displays a maroon spot. The filament is 1.5 cm long (Figure 3.19).

FIGURE 3.19  Globba pendula Roxb. (From Coll.: S. Emiza, K. Imin, and A. Angan. Flora of Malaya. Forest Research of Malaya. No. 59485. Loc.: Malaysia, Perak, Kuala Kangsar, Bubu Forest Reserve, Gunung Bubu. Trail to Gunung Bubu from Ulu Kenas. Date: July 7, 2009.)

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Medicinal Plants of China, Korea, and Japan

Medicinal uses: In Malaysia, the rhizomes are used to make a drink given postpartum and it is used to expel worms from the intestines. Constituents: Globba pendula Roxb. contains a labdane diterpene, indirubin, vanillin, vanillic acid, 2(3H)-benzoxazolone, as well as beta-sitosteryl-beta-d-glucopyranoside, betasitosterol, 7-alpha-hydroxysitosterol, and isoandrographolide.168 Pharmacology: Isoandrographolide displayed remarkable cytotoxic properties against human breast adenocarcinoma (MCF-7), human prostate cancer (PC-3), and human large-cell lung cancer (NCI-H460) cells cultured in vitro with IC50 values of 7.9, 8.7, and 9.0 μM, respectively.168 One might be curious to assess the anthelminthic potential of isoandrographolide. O OH

O

CH3

HO H3C

H

CH2

OH

Isoandrographolide

Bioresource: In vitro pharmacological study of isoandrographolide for its effect on cancer. The next plant discussed in this section is Globba schomburgkii Hook. f. 3.1.2.2.17  Globba schomburgkii Hook. f. [From Indonesian galoba, and after the German explorer, and botanist Moritz Richard Schomburgk (1811–1891)] History: This plant was first formally described in Botanical Magazine by Sir Joseph Dalton Hooker in 1876. Hooker (1817–1911) was a British botanist. Common names: Ginger lily plant, yellow dancing ladies, shuang chi wu hua jiang (Chinese). Habitat: This perennial ginger grows in the rainforests of Burma, Thailand, and Vietnam. It is cultivated as an ornamental plant for gardens. Diagnosis: The pseudostems of Globba schomburgkii Hook. f. are 50 cm tall. The ligule is short. The petiole is 0.5 cm long. The blade is linear or lanceolate, 15 cm × 3 cm to 20 cm × 4.5 cm, glabrous, obtuse at the base, and acuminate at the apex. The inflorescence is a pendulous raceme that is 3–10 cm long. The bracts are lanceolate and 1.2 cm long. The flowers are yellow. The calyx is campanulate and 0.5 cm long. The corolla tube is 1 cm long and hairy. The corolla lobes are ovate. The lateral staminodes are lanceolate and curved. The labellum is yellowish, cuneate, and bifid. The filament is curved and 1 cm long. The anther presents a pair of wing-like appendages. The ovary is tuberculate (Figure 3.20). Medicinal uses: In Laos, this plant is used to break fever. In Cambodia, Laos, and Vietnam, this plant is used to check bleeding and to heal wounds.

57

Superorder Lilianae Takht., 1967

FIGURE 3.20  Globba schomburgkii Hook. f. (From Coll.: C.W. Wang. Flora of Yunnan. FAN Memorial Institute of Biology. No. 75465. Loc.: Mixed forest, Che-li Hsian, China. Date: August 1936.)

Pharmacology: Apparently unknown. The plant produces kaempferol that is anti-inflammatory and could be implicated in the antipyretic and wound-healing properties mentioned above.163,169 OH HO

O

OH OH

O Kaempferol

In addition, kaempferol isolated from Impatiens balsamina L. (order Geraniales, family Balsaminaceae) compromised the growth of antibiotic-resistant Propionibacterium acnes and could be accountable for the antiseptic use of Globba schomburgkii Hook. f.170 Bioresource: In vitro pharmacological study of kaempferol for its effect on acne. The next plant discussed in this section is Globba variabilis Ridl. 3.1.2.2.18  Globba variabilis Ridl. [From Indonesian galoba, and from Latin variabilis = variable] History: This plant was first formally described in Transactions of the Linnean Society of London, Botany by Sir Henry Nicholas Ridley in 1893. Ridley (1855–1956) was a British botanist. Habitat: This perennial ginger grows in the rainforests of Malaysia.

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Medicinal Plants of China, Korea, and Japan

Diagnosis: Globba variabilis Ridl. is 30 cm tall. The leaves are obovate, cuspidate, glabrous, 25 cm long, and hairy. The sheaths are hairy. The peduncle is 25 cm long. The bracts are large, ovate, and orange. The panicle is short, dense, and 3 cm long. The branches are 1.5 cm long. The calyx is 0.5 cm long, short, hairy, and orange. The corolla is 0.75 cm long. The corolla lobes are ovate. The staminodes are linear, oblong, and blunt. The capsules are globose and orange. Medicinal uses: In Malaysia, this plant is used to heal sores and as a postpartum remedy. Pharmacology: Apparently unknown. Bioresource: Phytochemical and pharmacological studies and anti-inflammatory agent(s). The next plant discussed in this section is Hedychium coronarium J. König.

3.1.2.2.19  Hedychium coronarium J. König [From Greek hedys = sweet, and chion = snow, referring to the sweet-scented white flowers, and from Latin coronarium = used for or belonging to garlands] History: This plant was first formally described in Observationes Botanicae by Johann Gerhard König in 1783. König (1728–1785) was a German botanist. Common names: Ginger lily, white ginger, ganda suli (Malay), jiang hua (Chinese), hanashukusya (Japanese), kkot saeng gang (Korean). Synonyms: Hedychium coronarium var. baimao Z.Y. Zhu, Hedychium coronarium var. chrysoleucum Bak., Hedychium spicatum Buch.-Ham. ex Sm. Habitat: This perennial ginger grows in the forests of China, Taiwan, Bhutan, India, Indonesia, Malaysia, Burma, Nepal, Sri Lanka, Thailand, Vietnam, and Australia. It is native to India and cultivated as an ornamental plant. Diagnosis: The pseudostems of Hedychium coronarium J. König are 2 m tall. The leaves are sessile. The ligule is 2.5 cm long and membranaceous. The blade is oblong, 20 cm × 4.5 cm to 40 cm × 9 cm, hairy, and acute at the apex. The spike is elliptical and 10 cm × 5 cm to 20 cm × 8 cm. The bracts are imbricate, ovate, 4.5 cm × 2.5 cm, and have 2 or 3 flowers. The flowers are pure white, showy, and fragrant. The calyx is 4 cm long and split on one side. The corolla tube is 8 cm long and slender. The lobes are lanceolate and 5 cm long. The central lobe is spatulate and mucronate. The lateral staminodes are oblong and 5 cm long. The labellum is whitish, obcordate, 5 cm wide, and bifid. The filament is 3 cm long. The anther is 1.5 cm long. The ovary is sericeous (Figures 3.21 and 3.22). Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used to invigorate. In Indonesia, this plant is used to gargle, to soothe swellings, and to break fever. In the Philippines, this plant is used to treat tonsillitis. O

O O

CH3

O CH3

CH2

CH2

OH H3C

CH3 Hedychilactone A

H3C

CH3

OH

Hedychilactone B

59

Superorder Lilianae Takht., 1967

Pharmacology: The anti-inflammatory property of Hedychium coronarium J. König has been validated: extracts of the plant exhibited analgesic and anti-inflammatory properties in the acetic acid-induced abdominal writhing experiment and the carrageenan-induced paw edema experiment, respectively, on probable account of the labdane diterpenes hedychilactones A, B, and C.171,172 O OH

O

CH3

H3C CH3

CH2

H

Isocoronarin D

Other labdane diterpenes of interest found in this plant are coronarin A, B, C, and D that are cytotoxic.173,174 Isocoronarin D isolated from this plant elicited compelling cytotoxic potencies in  vitro against human hepatocellular carcinoma (S102), human bile duct epithelial carcinoma (HuCCA-1), human lung adenocarcinoma epithelial (A549), human malignant T-lymphoblastic (MOLT-3), human nasopharyngeal carcinoma (KB), human epithelial cervical cancer (Hela), human breast cancer (MDA-MB231), human promyelocytic leukemia (HL-60), mouse leukemia (P388), and human hepatocellular liver carcinoma (HepG2) cells cultured in vitro.175

FIGURE 3.21  Hedychium coronarium J. König. (From Det.: Singapore. Forest Research Institute, Kepong, Malaysia. Ref. F.R.I. 42/38 (II). N.B. A 613. Date: April 21, 1950.)

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.22  (See color insert.) Hedychium coronarium J. König.

Besides, coronarin C protected primary cultured mouse hepatocytes against d-galactosamineinduced cellular damage.176 The rhizomes of Hedychium coronarium König contain an antimicrobial essential oil with trans-meta-mentha-2,8-diene, linalool, 1,8-cineole, beta-pinene, and alpha-terpineol.177,178 Bioresource: In vitro pharmacological study of isocoronarin D for its effect on cancer. The next plant discussed in this section is Hedychium longicornutum Griff. ex Baker. 3.1.2.2.20  Hedychium longicornutum Griff. ex Baker [From Greek hedys = sweet, and chion = snow, referring to the sweet-scented white flowers, and longicornutum = with long horn] History: This plant was first formally described in The Flora of British India by John Gilbert Baker in 1892. Baker (1834–1920) was a British botanist. Common names: Ubat chaching, tepus lada (Malay). Habitat: This perennial ginger grows on small trees in the rainforests of Malaysia and Indonesia. It is cultivated as an ornamental plant. Diagnosis: The root of Hedychium longicornutum Griff. ex Baker is large, thick, and fleshy. The pseudostems are 60 cm tall. The leaves are cuneate, hairy, and 30 × 12 cm. The ligule is 6 cm long. The sheath is hairy. The spike is 12 cm long. The lower bracts are ovate. The upper bracts are lanceolate, brown, and silky. The calyx is spathaceous, oblique, pink, and 3 cm long. The corolla is 9 cm long. The corolla lobes are narrow, linear, and red. The filament is 15 cm long and pinkish white. The anther is linear and orange. The capsules are oblong, hairy, brown, and contain 15 seeds that are embedded in a crimson aril (Figure 3.23). Medicinal uses: In Malaysia, the roots are used to assuage earache and to expel worms from the intestines. Pharmacology: One could reasonably infer that the vermifuge property of the plant implies the presence of some nematocidal labdane diterpenes. Bioresource: Isolation of nematocidal labdane diterpenes. The next plant discussed in this section is Hedychium spicatum Buch.-Ham. ex Sm.

Superorder Lilianae Takht., 1967

61

FIGURE 3.23  Hedychium longicornutum Griff. ex Baker. (From Coll.: Y.Y. Sam and H. Othman. Flora of Malaya. Forest Research Institute Malaysia. Loc.: Malaysia, Baling, Kedah. Date: April 26, 2001.)

3.1.2.2.21  Hedychium spicatum Buch.-Ham. ex Sm. [From Greek hedys = sweet, and chion = snow, referring to the sweet-scented white flowers, and from Latin spicatum = with flowers in spikes] History: This plant was first formally described in The Cyclopaedia; or, Universal Dictionary of Arts by Francis Buchanan-Hamilton in 1811. Buchanan-Hamilton (1762–1829) was a Scottish physician. Common names: Spiked ginger lily, cao guo yao (Chinese), sanna (Japanese). Habitat: This perennial ginger grows in the forests of China, Taiwan, Bhutan, India, Burma, Nepal, and Thailand. The plant is cultivated for its fragrance and beauty. Diagnosis: The rhizome of Hedychium spicatum Buch.-Ham. ex Sm. has a characteristic bitter camphor-like taste and a strong aromatic odor. The pseudostems are 1 m tall. The leaves are sessile. The ligule is 2.5 cm long and membranaceous. The blade is elliptical, 10–3 cm × 40–10 cm, and acute at the apex. The spike is 20 cm long and laxly flowered. The bracts are oblong, 3 cm long, and have a single flower. The flowers are fragrant. The calyx is 3.5 cm long and trifid. The corolla is pale yellowish. The corolla tube is 8 cm long. The corolla lobes are linear, 2.5 cm long, and purplish. The lateral staminodes are white and bilobed. The lobes are clawed and acute at the apex. The labellum is yellowish. The filament is pale reddish. The capsules are globose, 2.5 cm in diameter, and have 3 valves. Each valve contains 6 seeds (Figure 3.24). Medicinal uses: In China, the plant is used to treat stomachache and toothache. In Taiwan, the plant is used to cure flatulence. In India, the essential oil of this plant has been used to perfume soaps, hair oils, face powders, and incenses. Pharmacology: The carminative property of the plant is most probably owed to the essential oil it produces. The essential oil extracted from Hedychium spicatum Buch.-Ham. ex Sm. abrogated the survival of Pediculus humanus capitis.179 Besides, extracts of rhizomes inhibited the growth of both Gram-positive and Gram-negative bacteria.180 Hedychium spicatum Buch.-Ham. ex Sm. contains series of labdane diterpenes that abrogated the

62

Medicinal Plants of China, Korea, and Japan

FIGURE 3.24  Hedychium spicatum Buch.-Ham. ex Sm. (From Coll.: L. Wray. Perak Museum Herbarium. Flora of the Malay Peninsula.)

s­ urvival of human colon adenocarcinoma (Colo-205), human epithelial carcinoma (A-431), human breast adenocarcinoma (MCF-7), and human lung adenocarcinoma epithelial (A549) cells cultured in vitro.181 The anti-inflammatory property of the plant is owed to hedychenone.182 Note that some other labdane diterpenes extracted from this plant inhibited the enzymatic activity of alpha-glucosidase.183 O CH3

H3C

CH3

CH3

O

Hedychenone

Bioresource: In vitro pharmacological study of hedychenone for its effect on cancer. The next plant discussed in this section is Kaempferia rotunda L. 3.1.2.2.22  Kaempferia rotunda L. [After Engelbert Kaempfer (1651–1716), chief surgeon for the East India Company, and from Latin rotunda = round] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Indian crocus, kunchur (Malay), hai nan san qi (Chinese). Habitat: This peculiar ginger grows in open grasslands and rainforests in China, Taiwan, India, Indonesia, Malaysia, Burma, Sri Lanka, and Thailand. It is also cultivated as an ornamental plant.

63

Superorder Lilianae Takht., 1967

Diagnosis: The rhizome of Kaempferia rotunda L. is tuberous. The ligule is broadly triangular and 0.3 long. The petiole is 2 cm long and channeled. The blade is pale green above, purplish below, lanceolate, 17 cm × 7.5 cm to 25 cm × 9.5 cm, and cuneate at the base. The inflorescence is sessile, with 4–6 flowers, and emerges from the rhizome before the leaves. The flowers are fragrant. The bracts are light purple-brown. The bracteoles are 2 cm long and the apex is bifid. The calyx is 4.5–7 cm long and trifid. The corolla lobes are spreading, white, linear, and 5 cm long. The lateral staminodes are erect, white, lanceolate, 5 cm × 1.5 cm, and acute at the apex. The labellum is lilac, orbicular, and bifid. The gynoecium is 0.5 cm long and hairy (Figure 3.25). Medicinal uses: In Malaysia, the rhizomes are used to treat flatulence. In Indonesia, this plant is used to cure indigestion. In the Celebes, a bath of this plant is said to cure all sickness. In the Philippines, the rhizomes are used to mitigate stomachache and to heal wounds.

O O Benzyl benzoate

Pharmacology: The carminative and digestive properties of Kaempferia rotunda L. are likely to be due to the essential oil that is present in the rhizomes. The essential oil contains mainly benzyl benzoate, n-pentadecane, and camphene.184 Benzyl benzoate exhibited insecticidal property against neonate larvae of Spodoptera littoralis with an LC50 value of 5.6 μg/cm2.185 Other insecticidal constituents in the plant are unusual series of cyclohexane derivatives that displayed antifeedant activity against larvae of Spodoptera littoralis.186

FIGURE 3.25  Kaempferia rotunda L.

64

Medicinal Plants of China, Korea, and Japan

Besides, the plant contains 1,2′-hydroxy-4,4′,6′-trimethoxy-chalcone that showed a remarkable antioxidant effect in the 2,2-diphenyl-1-picrylhydrazyl experiment.187 3-Deacetylcrotepoxide isolated from this plant inhibited the aggregation of platelets induced by arachidonic acid.188 The wound-healing property of the plant has not been yet substantiated, but such a property has been observed in the case of Kaempferia galanga L.189 Bioresource: In vitro pharmacological study of 1, 2′-hydroxy-4,4′,6′-trimethoxy-chalcone for its effect on skin ageing. The next plant discussed in this section is Phaeomeria imperialis Lindl. 3.1.2.2.23  Phaeomeria imperialis Lindl. [From Greek phaios = dark, and meris = part, and from Latin imperialis = majestic] History: This plant was first formally described in An Introduction to the Natural System of Botany by John Lindley in 1836. Lindley (1799–1865) was a British botanist. Common names: Torch ginger, porcelain rose, kantan (Malay). Basionym: Alpinia magnifica Roscoe. Synonyms: Nicolaia eliator (Jack) Horan., Nicolaia speciosa Horan., Phaeomeria speciosa Horan. Habitat: It is a perennial ginger found in Malaysia, Thailand, and Indonesia. It is cultivated as an ornamental plant and for food. The flower buds are used in several Malaysian and Thai dishes. Diagnosis: The pseudostems of Phaeomeria imperialis Lindl. are 3 m tall. The leaves are glabrous and 60 cm × 35 cm. The peduncle is 90 cm tall. The spike is cone-shaped, pinkish-red, and up to 15 cm long. The involucral bracts are ovate, oblong, spreading, pink, 12 cm × 6 cm, and fleshy. The floral bracts are linear and pink. The corolla tube is 3 cm long and dark red. The corolla lobes are lorate and golden yellow. The fruits are green, hairy, and 3 cm in diameter (Figure 3.26). Medicinal uses: In Malaysia, this plant is used to alleviate earache and to wash wounds. In Indonesia, the leaves are used as perfume.

FIGURE 3.26  (See color insert.) Phaeomeria imperialis Lindl.

65

Superorder Lilianae Takht., 1967

Pharmacology: One might be curious to study the pharmacological properties of members of the genus Phaeomeria Lindl. Bioresource: Phytochemical and pharmacological investigations and cosmetology. The next plant discussed in this section is Zingiber chrysostachys Ridl. 3.1.2.2.24  Zingiber chrysostachys Ridl. [From Prakrit singabera = ginger, and from Greek chryso = golden, and stachys = spike] History: This plant was first formally described in Journal of the Straits Branch of the Royal Asiatic Society by Sir Henry Nicholas Ridley in 1899. Ridley (1855–1956) was a British botanist. Habitat: This perennial ginger grows in the rainforests of Malaysia. Diagnosis: The pseudostems of Zingiber chrysostachys Ridl. are slender, 60 cm tall, and purplish. The leaves are elliptical, acuminate or acute, and 15 cm × 4.5 cm. The ligule is 3 cm long. The peduncles are 6 cm long and thick. The spike is 15 cm long and cylindrical. The bracts are broad, truncate, retuse, and yellow. The corolla is white. The corolla lobes are lanceolate acute and 3 cm long. The lip is narrow and linear. The lobes are ovate, blunt, and white. The midlobe is bifid dotted crimson. The anther cells are elliptical and pink spotted (Figure 3.27). Medicinal use: In Malaysia, this plant is used to break fever. Pharmacology: Apparently unknown. Note that Zingiber officinale Roscoe contains [8]-paradol and [8]-shogaol that inhibited the enzymatic activity of cyclooxygenase-2.190 Therefore, one can reasonably frame the hypothesis that the antipyretic property of Zingiber chrysostachys Ridl. involves some alkylphenols or arylheptanoids. O H3CO

HO

CH3

[8]-Shogaol

FIGURE 3.27  Zingiber chrysostachys Ridl. (From Perak Museum Herbarium. Flora of the Malay Peninsula. Coll.: L. Wray.)

66

Medicinal Plants of China, Korea, and Japan

Bioresource: In vitro pharmacological study of [8]-shogaol for its effect on inflammation. The next plant discussed in this section is Zingiber griffithii Backer. 3.1.2.2.25  Zingiber griffithii Baker [From Prakrit singabera = ginger, and after Dr. William Griffith (1810–1845), British surgeon and botanist in Malaysia] History: This plant was first formally described in The Flora of British India by John Gilbert Baker in 1892. Baker (1834–1920) was a British botanist. Common names: Tepus merah, tepus kechil (Malay). Habitat: This perennial ginger grows in the rainforests of Malaysia and Indonesia. Diagnosis: The pseudostems of Zingiber griffithii Baker grow to a height of 1 m. The leaves are elliptical, acuminate, hairy below, and 25 cm × 10 cm. The spikes are fusiform and 10–15 cm long. The peduncle is 10 cm long. The bracts are broad, ovate, hairy, pink, and 3 cm long. The calyx is spathaceous and 0.75 cm long. The corolla tube is 3 cm long. The corolla lobes are lanceolate, acute, and connate at the base. The midlobe is lanceolate. The anthers are brown with a yellow beak. Medicinal uses: In Malaysia, this plant is used for to break fever and to treat asthma. Pharmacology: Apparently unknown. The antipyretic property of Zingiber griffithii Backer could implicate some alkylphenols that could mediate the antiasthmatic property as well. For instance, [6]-gingerol isolated from Zingiber officinale Roscoe ­protected rodents against airway hyper-responsiveness in the ovalbumin aerosol experiment.191 O H3CO

HO

OH CH3

[6]-Gingerol

Bioresource: In vitro pharmacological study of [6]-gingerol for its effect on allergies. The next plant discussed in this section is Zingiber mioga (Thunb.) Rosc. 3.1.2.2.26  Zingiber mioga (Thunb.) Rosc. [From Prakrit singabera = ginger, and from Japanese myoga = Zingiber mioga (Thunb.) Rosc.] History: This plant was first formally described in Systemat Vegetabilium. Editio Decima Quarta by Carl Peter Thunberg in 1784. Thunberg (1743–1828) was a Swedish botanist. Common names: Myoga ginger, rang he (Chinese), myoga (Japanese), yang ha (Korean). Synonyms: Amomum mioga Thunb., Zingiber echuanense Y.K. Yang, Zingiber oligophyllum K. Schum.

67

Superorder Lilianae Takht., 1967

Habitat: This perennial ginger grows in moist places in the mountain valleys of China and Japan. The plant is often cultivated for its edible flower buds. Diagnosis: The rhizome of Zingiber mioga (Thunb.) Rosc. is yellowish. The ligule is bilobed, 0.3–1.2 cm long, and membranaceous. The petiole is 1.5 cm long. The blade is narrowly elliptical, 20 cm × 5 cm to 35 cm × 6 cm, and acute or acuminate at the apex. The inflorescence is elliptical and 5–7 cm long. The peduncle is 15 cm long. The bracts are reddish and elliptical. The calyx is 3 cm long. The corolla lobes are yellowish, lanceolate, membranaceous, and 3 cm × 0.5 cm. The labellum is ovate and 3 cm long. The central lobe is yellow and 2.5 cm × 1.5 cm. The lateral lobes are 1.3 cm × 0.5 cm. The anther is 1 cm long. The connective appendage is 1 cm long. The capsules are ovoid and loculicidally dehiscent. The seeds are embedded in a white aril (Figure 3.28). Medicinal uses: In China, this plant is used to treat malaria, insect bites and inflammation of the eyes. Pharmacology: The diterpenes galanals A and B isolated from the flowers of Zingiber mioga (Thunb.) Rosc. showed a remarkable cytotoxic effect against Jurkat human T-cell leukemia via apoptosis induction.192 Besides, galanals A and B are antimicrobial and probably antiplasmodial.75 CHO CHO CH3

CH3 O

H

CHO CHO

H3C



CH3 Galanal A

H3C



FIGURE 3.28  Zingiber mioga (Thunb.) Rosc.

H CH3 Miogadial

OH

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Medicinal Plants of China, Korea, and Japan

The anti-inflammatory property of the plant is confirmed: the plant contains a labdane diterpene that inhibited the aggregation of platelets and inhibited the enzymatic activity of 5-lipoxygenase.193 Other labdane diterpenes found in the plant are miogadial and mioganal 1 that are pungent.194 Note that miogadial is a potent transient receptor potential cation channel A1 agonist.195 One might be curious to look for antiplasmodial agents in this plant. Bioresource: In vitro pharmacological study of galanal A for its effect on cancer. The next plant discussed in this section is Zingiber ottensii Valeton. 3.1.2.2.27  Zingiber ottensii Valeton [From Prakrit singabera = ginger, and after Ottens, assistant of Carl Theodoric Valeton] History: This plant was first formally described in Bulletin du Jardin Botanique de Buitenzorg by Carl Theodoric Valeton in 1918. Valeton (1855–1929) was a Dutch botanist. Common name: Lempoyang hitam (Malay). Habitat: This perennial ginger is common in orchards, gardens, and waste grounds of Malaysia and Indonesia. It is cultivated for food and as an ornamental plant. Diagnosis: The rhizome of Zingiber ottensii Valeton is dark purple inside. The pseudostems are 50 cm tall. The leaves are 12 cm × 7.5 cm to 20 cm × 9 cm, elliptical or lanceolate, acuminate at the apex, and round at the base. The petiole is minute and hairy. The spike is elliptical and 15 cm long. The bracts are bright red and retuse. The flowers are pinkish. The calyx is 1.5 cm long and bilobed. The corolla tube is 5 cm long. The lip is oblong, acute, and emarginate. The staminodes are ovate (Figure 3.29). Medicinal uses: In Malaysia, this plant is used as a sedative for convulsion, as a postpartum remedy, and to treat lumbago. Constituents: The rhizomes of Zingiber ottensii Valeton are known to contain humulene, zerumbone, zerumbone epoxide, and labdane diterpenes including ottensin.196,197

FIGURE 3.29  Zingiber ottensii Valeton. (From Coll.: H.N. Ridley. Flora of Kedah. Date: June 1893.)

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Superorder Lilianae Takht., 1967

Pharmacology: Note that zerumbone may account for the analgesic property of the plant as zerumbone isolated from Zingiber zerumbet (L.) Roscoe ex Sm. elicited potent analgesic activity in the acetic acid-induced abdominal writhing experiment and the hot plate experiment.198 One could possibly think of GABAergic labdane diterpenes or arylheptanoids. O CH3 O

O CH3

CH2

CH3

H3C



H3C

CH3

Zerumbone



CH3 Ottensin

Bioresource: In vitro pharmacological study of zerumbone for its effect on cancer. The next plant discussed in this section is Zingiber purpureum Roxb. 3.1.2.2.28  Zingiber purpureum Roxb. [From Prakrit singabera = ginger, and from Latin purpureum = purple] History: This plant was first formally described in Asiatic Researches by William Roxburgh in 1810. Roxburgh (1751–1815) was a Scottish botanist. Common names: Cassumunar ginger, Bengal ginger, bangle, bonglai putih (Malay). Synonym: Zingiber cassumunar Roxb. Habitat: It is a perennial ginger native to India, Cambodia, Laos, and Vietnam. Diagnosis: The rhizome of Zingiber purpureum Roxb. is thick and yellow inside. The pseudostems are 1 m tall. The leaves are elliptical or oblong, hairy below, and 29 cm × 6 cm to 55 cm × 10 cm. The peduncle is 35 cm long. The spike is cylindrical. The bracts are ovate, 4.5 cm long, reddish, and hairy. The calyx tube is 1.5 cm long. The corolla tube is pure white and 3 cm long. The midlobe is orbicular and bilobed. The capsules are small and globose (Figure 3.30). Medicinal uses: In Laos, this plant is used to treat poisoning, fever, diarrhea, and abscesses. In Malaysia, this plant is used to mitigate stomachache, to treat rheumatism, to expel worms from the intestines, and as a postpartum remedy. In Indonesia, this plant is used to cure fatigue, flatulence, diarrhea, constipation, headache, cramps, obesity, and jaundice. Pharmacology: The carminative and digestive properties of Zingiber purpureum Roxb. are most probably due to the essential oil present in the rhizomes. Note that this essential oil abrogated the survival of a broad spectrum of bacteria, dermatophytes, and yeasts cultured in vitro, hence the use of the plant to heal abscesses.199 In addition, an extract of the plant exhibited remarkable antifungal properties against numerous human pathogenic fungi.200 Zingiber purpureum Roxb. contains a phenylbutenoid dimer that inhibited the multiplication of several human cancer cells cultured in vitro with IC50 values of 10–30 μM through a mechanism involving the enzymatic activity of cyclin-dependent protein kinases.201 Besides, the plant contains series of phenolic compounds that abrogated the survival of human lung adenocarcinoma epithelial (A549) cells cultured in vitro.202

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.30  Zingiber purpureum Roxb.

The anti-inflammatory and antipyretic properties of Zingiber purpureum Roxb. are well established: the plant contains series of phenylbutenoid dimers that inhibited the generation of prostaglandin E2 by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.203 Moreover, the plant contains a phenyl butadiene that mitigated the rat ear edema induced by ethyl phenylpropiolate, arachidonic acid, and 12-O-tetradecanoylphorbol-13-acetate.204 Furthermore, cassumunin A and B extracted from this plant protected rat thymocytes against H2O2-induced cellular damage.205 Besides, phlain III and cassumunaquinone 1 extracted from this plant inhibited nitric oxide generation by macrophages stimulated with bacterial lipopolysaccharides.206 Finally, a phenyl butadiene extracted from the plant exhibited an anti-inflammatory property in the carrageenan-induced paw edema experiment and an analgesic property in the acetic acid-induced abdominal writhing experiment.207 Bioresource: In vitro pharmacological study of cassumunin A for its effect on neurodegeneration. The next plant discussed in this section is Zingiber spectabile Griff. 3.1.2.2.29  Zingiber spectabile Griff. [From Prakrit singabera = ginger, and from Latin spectabile = spectacular] History: This plant was first formally described in Notulae ad Plantas Asiaticas of William Griffith in 1851. Griffith (1810–1845) was a British botanist. Common names: Golden beehive ginger, nodding gingerwort, tepus tanah (Malay). Habitat: This superb perennial ginger is common in the rainforests of Malaysia and Indonesia. It is cultivated as an ornamental plant. Diagnosis: The pseudostems of Zingiber spectabile Griff. are 2 m tall. The leaves are oblong, acuminate, and 30 cm × 10 cm. The peduncle is stout and 30 cm long. The spike is cylindrical, showy, 30 cm long, and thick. The bracts are stiff, ovate, red, and recurved. The calyx is spathaceous, 4.5 cm long, and white. The corolla tube is 4.5 cm long. The corolla lobes are lanceolate and acute. The side lobes are broad and round. The midlobe is bifid, yellow, and purplish. The anthers are broad and yellow, with an appendage that is long and purple (Figure 3.31).

Superorder Lilianae Takht., 1967

71

FIGURE 3.31  Zingiber spectabile Griff. (From Coll.: M.R. Henderson. Malay Peninsula. State of Perak. No. 23818. Loc.: Malaysia, Gunung Runto, Lenggong. Date: June 11, 1930.)

Medicinal use: In Malaysia, this plant is used to treat inflammation of the eyes. Pharmacology: Zingiber spectabile Griff. contains the sesquiterpene lactone zerumbone that was found to be cytotoxic against human colon adenocarcinoma (SW480) cells cultured in vitro achieving an IC50 value of 13 μg/mL.208 With regard to the anti-inflammatory property mentioned above, one can reasonably assume the involvement of some arylheptanoids, which are yet to be identified, and/or zerumbone.209,210 Bioresource: Phytochemical study and in vitro pharmacological study of zerumbone for its effect on colon cancer. Zerumbone is found in abundance in Zingiber zerumbet (L.) Roscoe ex Sm., discussed next. 3.1.2.2.30  Zingiber zerumbet (L.) Roscoe ex Sm. [From Prakrit singabera = ginger, and zerumbet = unknown origin] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Shampoo ginger, pine cone lily, lempoyang (Malay), hong qiu jiang (Chinese). Basionym: Amomum zerumbet L. Synonyms: Amomum silvestre Poir., Amomum spurium (Koen. in Retz.) Gmel., Amomum zerumbet L., Zerumbet zingiber Lestib. Habitat: This perennial ginger of fine form grows in moist places in the forests of China, Taiwan, Cambodia, India, Laos, Malaysia, Burma, Sri Lanka, Thailand, and Vietnam. Diagnosis: The rhizome of Zingiber zerumbet (L.) Roscoe ex Sm. is yellowish inside, edible, and tuberous. The pseudostems are 1 m tall. The leaves are sessile. The ligule is entire and 1.5–2 cm long. The blade is oblong or elliptical, 15 cm × 3 cm to 40 cm × 10 cm, hairy below, narrowed at the base, and acuminate or acute at the apex. The inflorescence is

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.32  Zingiber zerumbet (L.) Roscoe ex Sm. (From Coll.: L.G. Saw. Flora of Malaya. Forest Research Institute Malaysia. No. FRI 44285. Loc.: Malaysia. Perak, Hulu Perak, Lenggong, 5°70′N–100°57′E. In secondary lowland dipterocarp forest. Alt.: 90 m. Date: August 14, 1999.)

c­ onical, 6 cm × 3.5 cm to 15 cm × 5 cm, and obtuse. The peduncle is 30 cm long. The bracts are closely imbricate, obtuse, red, hairy, and membranaceous. The bracteoles are 1.5 cm long. The calyx is 2 cm long, membranaceous, and trifid. The corolla tube is 3 cm long and slender. The corolla lobes are pale yellow and lanceolate. The labellum is yellow and 2.5 cm long. The lateral lobes are ovate and 1 cm long,. The stamen is 1 cm long. The connective appendages are 0.8 cm long. The ovary is 0.5 cm long. The capsules are elliptical, 1 cm long, and enclose numerous black seeds (Figure 3.32). Medicinal uses: In China, this plant is used to treat indigestion. In Cambodia, Laos, and Vietnam, this plant is used to cure fatigue, to treat convulsion and constipation, and to break fever. In Indonesia, this plant is used to treat indigestion. In the Philippines, this plant is used to treat diarrhea, asthma, and rheumatism. In Papua New Guinea, this plant is used to abrogate the fertility of women. The milky juice extracted from the inflorescence is used as a shampoo in Hawaii. Pharmacology: The carminative property of Zingiber zerumbet (L.) Roscoe ex Sm. is most probably owed to the essential oil stored in the rhizomes. Besides, the rhizomes store a significant amount of zerumbone that has displayed so far an impressive array of pharmacological activities, including immunomodulatory, analgesic, proapoptotic, anticancer, anti-human immunodeficiency virus, and anti-inflammatory activities.198,209,211–215 OH HO

O

OCH3 OH

O

3-O-Methyl kaempferol

73

Superorder Lilianae Takht., 1967

Other anti-inflammatory agents found in the plant are 5-hydroxyzerumbone, zerumboneoxide, and 3-O-methyl kaempferol that inhibited the generation of nitric oxide by macrophages stimulated with bacterial lipopolysaccharides.210,216 CH3

OH

O

CH3

H3C

CH3

5-Hydroxyzerumbone

Bioresource: In vitro pharmacological study of zerumbone for its effect on human immunodeficiency virus infection. Anti-inflammatory agents are common in the next clade: the order Poales.

3.1.3  Order Poales Small, 1903 The order Poales consists of 16 families of flowering plants of which the Cyperaceae is discussed here. 3.1.3.1  Family Cyperaceae Juss., 1789, nom. cons., the Sedge Family The family Cyperaceae is a vast and successful clade that consists of 70 genera and nearly 4000 species of rhizomatous sedges, mainly known to contain series of stilbenes, quinones, and flavonoids of pharmaceutical interest. The stems of Cyperaceae are often sharply angled and bear at the apex a head of leaves that are simple, alternate, arranged in 3 whorls, and endowed with a closed sheath. The flowers are arranged in spikes or spikelets. The perianth consists of 1 to several bristles. The androecium consists of 1–6 stamens that open longitudinally. The anthers are tetrasporangiate and dithecal. The gynoecium consists of 2–3 carpels forming a compound, unilocular, and superior ovary. The fruits are trigonous or lenticelled nutlets. Formerly official in a number of Western pharmacopoeia were the rhizomes of Carex arenaria L. and Cyperus rotundus L. Cyperus papyrus L. was used to make paper in ancient Egypt. Cyperaceae are interesting because they contain heteropolymers of resveratrol that might be of chemotherapeutic and cosmetological interest. So far, the family has not been quite well studied for pharmacology. The first plant examined in this section is Cyperus cyperoides (L.) Ktze. 3.1.3.1.1  Cyperus cyperoides (L.) Ktze. [From Latin cyperus = from a Greek word meaning sedge, and cyperoides = cyperus-like] History: This plant was first formally described in Mantissa Plantarum by Carl Linnaeus in 1771. Linnaeus (1707–1778) was a Swedish botanist. Common names: Pacific island flat sedge, zhuan zi miao (Chinese), inu kugu (Japanese), bang dong sa ni a jae bi (Korean). Habitat: This perennial sedge is found in China, Taiwan, Bhutan, India (specifically Kashmir), Indonesia, Japan, Korea, Laos, Malaysia, Burma, Nepal, Pakistan, Papua New Guinea, the Philippines, Sri Lanka, Thailand, Vietnam, tropical Africa, Atlantic Ocean islands, Australia, Indian Ocean islands, Madagascar, and Pacific islands.

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.33  Cyperus cyperoides (L.) Ktze. (From Det.: J.H. Kern. Flora Malesiana. Loc.: Malaysia, Plantation Kepong, Selangor. Date: January 16, 1937; 1960.)

Diagnosis: The rhizome of Cyperus cyperoides (L.) Ktze. is short and hard. The culms are laxly tufted, 50 cm tall, triquetrous, smooth, and swollen at the base. The blade is ­0.3–0.5 cm wide. The 5–8 involucral bracts are leaf-like, longer than the inflorescence, and obliquely spreading. The inflorescence is a simple anthela. The 6–12 rays are and 6–14 cm long. The spikes are cylindrical, 1 cm × 0.5 cm to 2.5 cm × 1 cm, and present many dense spikelets. The spikelets are linear, 0.3 cm × 0.07 cm to 0.7 cm × 0.07 cm, and have 2 or 3 flowers. The glumes are yellow, oblong, and 0.3 cm long. The androecium includes 3 stamens that are broadly linear and minute. The style is short with 3  stigmas. The nutlets are dark brown, narrowly oblong, trigonal, and minute (Figure 3.33). Medicinal use: In Indonesia, this plant is used to expel worms from the intestines.

OH

O

H3C

O CH3

CH3 O

O

CH2

O

O O

O Cyperaquinones

CH2

75

Superorder Lilianae Takht., 1967 O CH3

OH

O Plumbagin

Constituents: Cyperus cyperoides (L.) Ktze. is known to contain tricin and luteolin as well as cyperaquinones.217,218 Pharmacology: One could infer that the anthelminthic property of the plant could be due to cyperaquinones as quinones such as plumbagin, which is common in the genus Plumbago L. (order Plumbaginales, family Plumbaginaceae), are known to negate the development of Haemonchus contortus and Ascaris sum.219 Bioresource: Isolation of anthelmintic cyperaquinones. The next plant discussed in this section is Cyperus esculentus L. 3.1.3.1.2  Cyperus esculentus L. [From Latin cyperus = from a Greek word meaning sedge, and esculentus = edible] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Yellow nut sedge, tiger nut, you suo cao (Chinese). Synonyms: Chlorocyperus aureus Pall., Chlorocyperus phymatodes (Muhl.) Pall., Cyperus aureus Ten., Cyperus buchananii Boeckeler, Cyperus chrysostachyus Boeckeler, Cyperus cubensis Steud., Cyperus fulvescens Liebm., Cyperus gracilescens Roem. & Schult., Cyperus gracilis Muhl., Cyperus heermannii Buckley., Cyperus helodes Schrad. ex Nees, Cyperus lutescens Torr. & Hook., Cyperus maritimus Bojer, Cyperus phymatodes Muhl., Cyperus repens Elliot, Cyperus retusus A. Rich., Cyperus ruficomus Buckley, Cyperus tenorianus Roem. & Schult., Cyperus tenorii C. Presl, Cyperus tuberosus Pursh. Habitat: It is an elegant perennial sedge native to the Mediterranean region that has spread in most parts of the world. It is cultivated for the oil and the starch produced by its tubers. Diagnosis: The tubers of Cyperus esculentus L. are gray, tomentose, aromatic, elliptical, and 1 cm × 0.5 cm to 3 cm × 0.8 cm. The culms are solitary, 10–40 cm tall, triquetrous, and smooth. The leaves are numerous and basal. The sheath is reddish brown. The blade is yellowish green, 0.5 cm wide, and revolute. The inflorescence is a simple or compound anthela. The 5–10 rays are 10 cm long. The spikes are ovoid and present 5–14 laxly arranged spikelets. The spikelets are distichous, linear, 1.5 cm × 0.1 cm, and have 10–20 flowers. The rachilla is broadly winged. The glumes are yellowish, laxly imbricate, ovate, 0.2 cm long, and have 7 nerves. The androecium comprises 3 stamens with linear anthers. The style is long and has 3 stigmas. The nutlets are brownish gray, elliptical, trigonal, glossy, and densely puncticulate (Figure 3.34). Medicinal uses: In Cambodia, Laos, and Vietnam, the tubers are eaten to cure fatigue and to treat indigestion. In Spain and South America, the tubers are used to make a milky drink called “horchata de chufa.”

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.34  Cyperus esculentus L. (From Det.: C.D. Adams. The New York Botanical Garden. Loc.: Trinidad, Savanah Drive, Trincity & C.H.R./Way. Date: April 29, 1981.)

Constituents: The tuber contains about 20% starch and some fixed oil.220,221 The volatile oil produced by this plant contains mainly 3-ethyl-2,5-dimethylpyrazine, n-hexanol, isoamyl alcohol, and limonene.222 Pharmacology: Apparently unknown. Bioresource: Phytochemical and pharmacological investigations, use of the tubers as a crop, and essential oil for cosmetology. The next plant discussed in this section is Cyperus malaccensis Lam. 3.1.3.1.3  Cyperus malaccensis Lam. [From Latin cyperus = from a Greek word meaning sedge, and malaccensis = from Malacca] History: This plant was first formally described in Tableau Encyclopédique et Méthodique des Trois Règnes de la Nature by Jean-Baptiste Pierre Antoine de Monet, Chevalier de la Marck in 1791. Lamarck (1744–1829) was a French botanist. Common names: Rumput kuluwing, suket adem (Indonesian), sititoi (Japanese). Synonym: Cyperus fortunei Steud. Habitat: This perennial sedge grows in tidal river beds of Malaysia, Indonesia, the Philippines, and Australia. Diagnosis: The rhizome of Cyperus malaccensis Lam. is stout, woody, and creeping. The stems are stout, triangular, and 90 cm tall. The leaves are few and short. The sheaths are 25 cm long. The bracts are long and broad. The umbels are 10 cm long. The rays are short. The spikelets are narrow linear, 1.5 cm long, and have 6–12 flowers. The glumes are boat-shaped, blunt, distant, reddish, and pale at the edge. The nutlets are oblong and trigonous (Figure 3.35). Medicinal use: In the Philippines, the rhizomes are used to excite the discharge of urine. Pharmacology: Apparently unknown. One might be curious to validate the diuretic property of Cyperus malaccensis Lam. Bioresource: Phytochemical and pharmacological investigations and diuretic agent(s). The next plant discussed in this section is Cyperus pilosus Vahl.

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Superorder Lilianae Takht., 1967

FIGURE 3.35  Cyperus malaccensis Lam. (From Coll.: C.F. Symington. Det.: J.H. Kern. Flora of Malay Peninsula. Forest Department. No. 43742. Loc.: Malaysia, Kuala Selangor. Date: June 30, 1936; 1960.)

3.1.3.1.4  Cyperus pilosus Vahl [From Latin cyperus = from a Greek word meaning sedge, and pilosus = hairy] History: This plant was first formally described in Enumeratio Plantarum by Martin Henrichsen Vahl in 1753. Vahl (1749–1804) was a Danish botanist. Common names: Hairy sedge, mao zhou suo cao (Chinese), oni gayatsuri (Japanese). Synonyms: Cyperus amuricus var. japonicus Kük., Cyperus marginellus Nees. Habitat: This stout perennial sedge grows in ditches and marshy wet grounds of Taiwan, Bangladesh, Bhutan, India, Indonesia, Japan, Malaysia, Burma, Nepal, Papua New Guinea, the Philippines, Sri Lanka, Thailand, Vietnam, Australia, and Pacific islands. Diagnosis: The stolons of Cyperus pilosus Vahl are slender. The culms are acutely triquetrous and 1 m tall. The leaves are 0.75 cm wide. The umbel is short and presents innumerable brown spikelets. The rays are few and 3–15 cm long. The rachis is hairy. The glumes are ovate, blunt, red, and loosely imbricate. The nutlets are ovate, acute, apiculate, triquetrous, brown, and minute (Figure 3.36). Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used to treat itches, jaundice, malaria, headache, rheumatism, epilepsy, urogenital infection, and hiccups and to excite the discharge of urine. OCH3 OH HO

O

OCH3

OH OH

OH

O Tricin

O Salicylic acid

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.36  Cyperus pilosus Vahl. (From Coll.: D.A. Simpson and R. Casserly. Ex Herb. Hort. Bot. Reg. Kew. Flora of Sabah. No. 89/205. Loc.: Malaysia, Ranau district, Kinabalu National Park. Date: November 3, 1989.)

Pharmacology: The anti-inflammatory property of Cyperus pilosus Vahl is confirmed: the flavonoid tricin isolated from the plant inhibited the enzymatic activity of cyclooxygenase-1 and cyclooxygenase-2 achieving an IC50 value of 1 μM.217,223 In addition, tricin extracted from Agelaea pentagyna (Lam.) Baill. (order Rosales, family Connaraceae) inhibited the exocytosis of rat basophilic leukemia (RBL-2H3) cells stimulated with antigens.224 Furthermore, tricin extracted from Wikstroemia indica (L.) C.A. Mey. (order Myrtales, family Thymelaeaceae) exhibited antileukemic properties.225 Another flavonoid contained in this plant is luteolin that exhibited a potent antiplasmodial property against Plasmodium falciparum.217,226 Moreover, luteolin protected rodents against CCl4-induced hepatocellular damage.227 Bioresource: In vitro pharmacological study of tricin for its effect on cancer. The next plant discussed in this section is Fimbristylis aestivalis (Retz.) Vahl. 3.1.3.1.5  Fimbristylis aestivalis (Retz.) Vahl [From Latin fimbriae = shreds, fringe, and stilus = style, and aestivalis = of the summer] History: This plant was first formally described in Observationes Botanicae by Anders Jahan Retzius in 1791. Retzius (1742–1821) was a Swedish botanist. Common names: Summer fimbri, xia piao fu cao (Chinese), jom min ha neul ji gi (Korean). Basionym: Scirpus aestivalis Retz. Synonym: Fimbristylis leiocarpa Maxim. Habitat: This annual little sedge is found in the grasslands and marshy places of China, Taiwan, Bhutan, India, Indonesia, Japan, Laos, Nepal, Papua New Guinea, the Philippines, Russia, Sri Lanka, Thailand, Vietnam, Australia, and Pacific islands. Diagnosis: The culms of Fimbristylis aestivalis (Retz.) Vahl are densely tufted, 3–25 cm tall, slender, flatly trigonal, smooth, and present a few leaves at the base. The leaves are shorter than the culms. The blade is filiform, flat, sparsely hairy, and somewhat involute. The 3–5

79

Superorder Lilianae Takht., 1967

involucral bracts are filiform and hairy. The inflorescence is a compound and lax anthela. The 3–7 rays are up to 3 cm long and slender. The spikelets are solitary, ovoid, 0.2 cm × 0.1 cm, and densely flowered. The glumes are spirally imbricate, reddish brown, ovate to oblong, and minute. The stamen is solitary. The anther is ovoid. The style is long and compressed, basally inflated, ciliate, and shows a pair of stigmas. The nutlets are ­yellow, sessile, ovoid, and minute (Figure 3.37). Medicinal use: In Malaysia, this plant is used to make a protective postpartum remedy. Pharmacology: To date, the pharmacological properties of the genus Fimbristylis Vahl are apparently unknown. OH OH HO

O

OCH3 OH

O

3-O-methylquercetin

3-O-methylquercetin isolated from the seeds of Carex folliculata L. (order Cyperales, family Cyperaceae) abated the survival of methicillin-resistant Staphylococcus aureus, achieving an IC50 value of 6.5 μM.228

FIGURE 3.37  Fimbristylis aestivalis (Retz.) Vahl. (From Coll.: C.M. Wang, H.M. Lin, and H.C. Liu. Det.: C.L. Wai. National Museum of Natural Science. Taichung, Taiwan, R.O. China. No. 03052. Loc.: Taiwan, on exposed site, Chunhsing bridge—Chiatulu, Manchou Hsiang, Pingtung Hsien, 120°48′29′E–22°21′17′N. Date: April 11, 1998.)

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Medicinal Plants of China, Korea, and Japan

Bioresource: In vitro pharmacological study of 3-O-methylquercetin for its effect on acne. The next plant discussed in this section is Fimbristylis diphylla (Retz.) Vahl. 3.1.3.1.6  Fimbristylis diphylla (Retz.) Vahl [From Latin fimbriae = shreds, fringe, and stilus = style in reference to the ciliate style, and diphylla = with 2 leaves] History: This plant was first formally described in Observationes Botanicae by Anders Jahan Retzius in 1779. Retzius (1742–1821) was a Swedish botanist. Common names: Frindge rushes, rumput parah, rumput purun batu (Malay), ni er ye piao fu cao (Chinese), kuro tentsuki (Japanese), ha neul ji gi (Korean). Basionym: Scirpus diphyllus Retz. Synonyms: Fimbristylis annua (All.) Roem. & Schult., Fimbristylis communis Kunth, Fimbristylis diffusula Steud., Fimbristylis polymorpha Boeckeler, Scirpus annuus All. Habitat: It is a gracile annual pantropical tufted sedge found in Asian waste grounds. Diagnosis: The rhizome of Fimbristylis diphylla (Retz.) Vahl is short. The culms are 50 cm tall and polygonal. The leaves are linear. The umbels are 3–25 cm wide. The rays are numerous. The spikelets are obovoid. The glumes are ovate, keeled, mucronate, glabrous, and green. The style is hairy. The nuts are ovoid and ribbed (Figure 3.38). Medicinal use: In Papua New Guinea, this plant is used to remove ringworm. Pharmacology: Apparently unknown. Parvisoflavones A and B isolated from Eriophorum scheuchzeri Hoppe (order Cyperales, family Cyperaceae) showed good activity against Candida albicans cultured in vitro.229 One could infer that quinones or flavonoids impart to Fimbristylis diphylla (Retz.) Vahl its antifungal property.

FIGURE 3.38  Fimbristylis diphylla (Retz.) Vahl. (From Coll.: Teruya L. Flora of Johor. Comm. Ex. Herb. Hort. Bot. Sing. Johor, Malaysia. N°2132. Date: December 18, 1932.)

81

Superorder Lilianae Takht., 1967 H3C H3C O

O

OH

O

Parvisoflavone A

H3C OH

O

O

H3C

OH

OH

OH

O

OH

Parvisoflavone B

Bioresource: In vitro pharmacological study of parvisoflavone A for its effect on candidiasis. The next plant discussed in this section is Scirpus ternatanus Reinw. ex Miq. 3.1.3.1.7  Scirpus ternatanus Reinw. ex Miq. [From Greek scleros = hard, and from Latin scirpus = name used by Pliny for a rush] History: This plant was first formally described in Flora van Nederlandsch Indië by Caspar Georg Carl Reinwardt in 1856. Reinwardt (1773–1854) was a Swedish botanist. Common name: Bai sui biao cao (Chinese). Synonyms: Scirpus chinensis Munro, Scirpus ternatensis C. B. Clarke. Habitat: This perennial sedge grows in the wet spots of China, Taiwan, Bhutan, India, Indonesia, Japan, Burma, Papua New Guinea, the Philippines, Thailand, Vietnam, and Pacific islands. Diagnosis: The culms of Scirpus ternatanus Reinw. ex Miq. are 1 m tall, stout, trigonal, and present several nodes. The basal sheaths are blackish purple and shiny. The blade is 1.5 cm wide, flat, stiff, and leathery. The inflorescence is a large compound anthela that is 10 cm wide. The rays are 5 or more in number, up to 10 cm long, stout, spreading, and smooth. The

FIGURE 3.39  Scirpus ternatanus Reinw. ex Miq. (From Coll.: R.J. Johns. Det.: D. Simpson. Flora of Mount  Jaya, Papua New Guinea, Indonesia. Date: December 1998. No. 9241. Loc.: Papua New Guinea, 4°15′S–137°1′E. Alt.: 1500–2300 m. Date: October 10, 1998.)

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spikelets are sessile, in head-like clusters of 4–10, ovoid, 0.3 cm long, and densely flowered. The glumes are brown, densely arranged, broadly ovate, and minute. The perianth presents 3 bristles that are scabrous, erect, and longer than the nutlets. The style is filiform, minute, and develops 3 stigmas. The nutlets are pale yellow, elliptical, and minute (Figure 3.39). Medicinal use: In Taiwan, this plant is used to heal wounds. Pharmacology: One could reasonably suggest that the healing property of this plant is owed to stilbenes. In fact, series of stilbenes including resveratrol, piceatannol, viniferin, scirpusin A, and scirpusin B isolated from Scirpus maritimus L. showed some level of cytotoxicity in vitro.230 Viniferin isolated from Vitis amurensis Rupr. (order Vitales, family Vitaceae) exhibited potent antibacterial properties against the Gram-negative Streptococcus mutans and Streptococcus sanguinis.231 Besides, resveratrol is anti-inflammatory and inhibits the growth of Gram-positive Propionibacterium acnes cultured in vitro.232 OH

OH HO Resveratrol

Bioresource: In vitro pharmacological study of viniferin as antibiotic. The next plant discussed in this section is Scleria levis Retz. 3.1.3.1.8  Scleria levis Retz. [From Greek scleros = hard, and from Latin levis = beardless] History: This plant was first formally described in Observationes Botanicae by Anders Jahan Retzius in 1786. Retzius (1742–1821) was a Swedish botanist. Common names: Mao guo zhen zhu mao (Chinese), shinju gaya (Japanese). Habitat: This obscure perennial sedge grows in China, Taiwan, Bangladesh, Bhutan, Cambodia, India, Indonesia, Japan, Laos, Malaysia, Burma, Nepal, Papua New Guinea, the Philippines, Sri Lanka, Thailand, Vietnam, Australia, and the Pacific islands. Diagnosis: The rhizome of Scleria levis Retz. is woody and covered with purple scales. The culms are laxly tufted, 70–90 cm × 0.3–0.5 cm, trigonal, scabrous, and hairy. The leaf sheath is 1–8 cm long. The blade is linear and 30 cm × 1 cm. The involucral bracts are leaflike and up to 15 cm long. The bractlets are hairy, auriculate at the base, and present barbate auricles. The inflorescence is paniculate with 1–2 lateral branches. The branches are 3 cm × 1.5 cm to 10 cm × 3 cm. The 1–2 spikelets are brown, unisexual, sessile, and 0.3 cm long. The male spikelets are narrowly ovoid. The glumes are 0.3 cm long, keeled, and membranaceous. The female spikelets are narrowly ovoid. The glumes are oblong-ovate, keeled, and rust-colored. The male flowers comprise 3 stamens. The anthers are minute and linear. The female flower comprises 3 stigmas. The nutlets are white, spherical, 0.2 cm in diameter, trigonal, and smooth (Figure 3.40). Medicinal use: In Malaysia, the nutlets are chewed to alleviate cough. Pharmacology: Members of the vast genus Scleria P.J. Bergius would be worth evaluating for pharmacology, as Efange and coworkers233 isolated an antiplasmodial sesquiterpene endoperoxide, okundoperoxide, from Scleria striatinux De Wild.

83

Superorder Lilianae Takht., 1967

FIGURE 3.40  Scleria levis Retz. (From Coll.: D.A. Simpson, R. Casserly, A. Lamb, and A. Phillips. Ex. Herb. Hort. Bot. Reg. Kew. Flora of Sabah. No. 89/183. Loc.: Malaysia, Tenom District, Tenom, Agricultural Research Station. Date: October 29, 1989.) CH3

O

O OH

O H3C

H CH3

H

CH3 Okundoperoxide

Bioresource: In vitro pharmacological study of okundoperoxide for its effect on malaria. The next plant discussed in this section is Scleria lithosperma (L.) Sw. 3.1.3.1.9  Scleria lithosperma (L.) Sw. [From Greek scleros = hard, and lithos = stone and sperma = seed] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common name: Shi guo zhen zhu mao (Chinese). Basionym: Scirpus lithospermus L. Synonyms: Carex lithosperma (L.) L., Carex lithosperma J.F. Gmel., Carex subulata J.F. Gmel., Carex subulata Schumach., Hypoporum lithospermum (L.) Nees, Hypoporum purpurascens Nees, Hypoporum sieberi Nees, Schoenus lithospermus (L.) L., Scirpus lithospermus L., Scleria capillaris R.Br., Scleria elongata J. Presl & C. Presl, Scleria elongata Piérart, Scleria filiformis Sw., Scleria glaucescens J. Presl & C. Presl, Scleria gracilis Rich., Scleria krugiana Boeckeler, Scleria lithosperma var. filiformis Britton, Scleria lithosperma var. multispiculata Govind., Scleria purpurea Poir., Scleria subulata Steud., Scleria tenuis Retz., Scleria wightiana Steud.

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Habitat: This unnoticed perennial sedge is found in the forests and rocky riverbanks of China, Taiwan, Bhutan, India, Indonesia, Malaysia, Burma, Papua New Guinea, the Philippines, Sri Lanka, Thailand, Vietnam, tropical Africa, America, Australia, Indian Ocean islands, and Pacific islands. Diagnosis: The rhizome of Scleria lithosperma (L.) Sw. is short, thick, woody, and creeping. The culms are tufted, 30 cm × 1.5 cm to 50 cm × 2 cm, trigonal, and glabrous. The glumes are brown. The basal leaves are sheath-like and bladeless. The cauline leaves present a trigonal sheath. The blade is narrowly linear, 0.2 cm wide, serrate, and caudate at the apex. The involucral bracts are leaf-like; the basal one up to 10 cm long and sheathing. The inflorescence is paniculate, 30 cm long, and develops 1–3 lateral branches. The spikelets are 0.4 cm long and present 4–5 glumes. The glumes are ovate-lanceolate, keeled, membranaceous, and mucronate at the apex. The nutlets are whitish, ovoid, 0.2 cm long, trigonal, reticulate, and shiny (Figure 3.41). Medicinal uses: In Malaysia, the roots are boiled in water and the liquid obtained is drunk postpartum. In the Philippines, the young shoots are eaten to treat enlarged stomach in children. In the Solomon Islands, this plant is used to break fever. Pharmacology: Apparently unknown. Bioresource: Phytochemical and pharmacological studies and antimalarial sesquiterpene endoperoxide(s). The next plant discussed in this section is Scleria pergracilis (Nees) Kunth. 3.1.3.1.10  Scleria pergracilis (Nees) Kunth [From Greek scleros = hard, and from Latin pergracilis = very slender] History: This plant was first formally described in Edinburgh New Philosophical Journal by Christian Gottfried Daniel Nees von Esenbeck in 1834. von Esenbeck (1776–1858) was a German botanist. Common names: Xian gan zhen zhu mao (Chinese), ae gi deok san pul (Korean). Basionym: Hypoporum pergracile Nees.

FIGURE 3.41  Scleria lithosperma (L.) Sw. (From Ex. Herb. Hort. Bot. Reg. Kew. Flora of Sabah. Loc.: Malaysia, Tenom District, Tenom, Agricultural Research Station. Coll.: D.A. Simpson, R. Casserly, A. Lamb, & A. Phillips. No. 89/183. Date: October 29, 1989.)

Superorder Lilianae Takht., 1967

Habitat: This delicate annual sedge grows in the grassy spots of China, Bangladesh, Cambodia, Malaysia, India (specifically Kashmir), Indonesia, Korea, Laos, Burma, Nepal, Papua New Guinea, the Philippines, Sri Lanka, Thailand, Vietnam, tropical Africa, and Australia. Diagnosis: The culms of Scleria pergracilis (Nees) Kunth are tufted, 30 cm long, erect, trigonal, sulcate, and glabrous. The contraligule is round. The blade is capiliform. The involucral bracts are hairy and 0.5 cm long. The bractlets are glume-like. The inflorescence is spicate, 2.5–8.5 cm long, and formed by clusters of 2–3 spikelets. The spikelets are bisexual, ovoid, and 0.3–9 cm long. The glumes are ovate, keeled, and mucronate at apex. The male flowers comprise 3 stamens. The female flowers present 3 stigmas. The nutlets are white, globose, and minute (Figure 3.42). Medicinal use: In Malaysia, this plant is boiled in water and the liquid obtained is drunk to treat gonorrhea. In Indonesia, this plant is boiled in water and the liquid obtained is drunk to break fever. This plant is eaten postpartum and is used to treat mouth diseases. Pharmacology: Apparently unknown. The flavonoid luteolin 5-methyl ether has been found in this plant.234 Bioresource: Phytochemical and pharmacological studies and antimalarial sesquiterpene endoperoxide(s). Scleria sumatrensis Retz. is discussed next. 3.1.3.1.11  Scleria sumatrensis Retz. [From Greek scleros = hard, and from Latin sumatrensis = from Sumatra] History: This plant was first formally described in Observationes Botanicae by Anders Jahan Retzius in 1789. Retzius (1742–1821) was a Swedish botanist. Common names: Nutrush, rumput sendayan (Malay), yin ni zhen zhu mao (Chinese). Synonym: Scleria fauriei Ohwi. Habitat: This tall perennial sedge grows by the rivers, marshes, and lakes of China, Taiwan, Cambodia, India, Indonesia, Laos, Malaysia, Burma, the Philippines, Sri Lanka, Thailand, Vietnam, Australia, Indian Ocean islands, and Pacific islands.

FIGURE 3.42  Scleria pergracilis (Nees) Kunth.

85

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.43  Scleria sumatrensis Retz. (From Coll.: A.T. Gwee and A. Samsuri. Flora of Singapore. Singapore Botanic Gardens Herbarium. No. 2007–600. Loc.: Singapore, Mandai Upper Pierce Extension. Date: November 15, 2007.)

Diagnosis: The culms of Scleria sumatrensis Retz. are 3 m tall, trigonal, and glabrous. The leaves are whorled. The sheaths are 5 cm long, papery, and glabrous. The ligule is circular, stumpy, and ciliate at the margin. The blade is linear, 40 cm × 1 cm, thickly papery, ­scabrous, and apically attenuate. The inflorescence is compound, paniculate, and develops several branches. The lateral branches are arranged in 2–3 clusters, 6 cm × 10 cm, spreading, and with angled axes. The involucral bracts are leaf-like, 25 cm long, and sheathing. The bractlets are hairy and dilated at the base. The spikelets are solitary or in pairs, brown, 0.5 cm long, and unisexual. The male spikelets are ovoid and truncate at the apex. The glumes are rust-colored, 0.35 cm long, membranaceous, and cuspidate at the apex. The female spikelets are narrowly ovoid and acuminate at the apex. The glumes are broadly ovate and keeled. The male flowers present 3 stamens. The anthers are linear and 0.1 cm long. The female flowers present 3 stigmas. The nutlets are flattened, globose, 0.2 cm in diameter, reticulate, hairy, and cuspidate at the apex (Figure 3.43). Medicinal uses: In Malaysia, the roots are boiled in water and the resulting liquid is drunk to treat gonorrhea. Pharmacology: Apparently unknown. Bioresource: Antibacterial agent(s). The next clade discussed in this chapter is the non-Commelinids.

3.2  NON-COMMELINIDS The non-Commelinids consist of seven orders: the Asparagales, Liliales, Pandanales, Dioscoreales, Petrosaviales, Alismatales, and Acorales. This group of plants, like the Commelinids, share a common ancestry with the Magnolianae from which they have inherited the ability to contain isoquinoline alkaloids of tremendous pharmaceutical interest. Besides, the non-Commenilids are notorious among flowering plants for accumulating large amounts of steroidal saponins that have so far displayed a broad array

Superorder Lilianae Takht., 1967

87

of cytotoxic activities. One could foresee with confidence this clade as a bioresource of steroidal saponins, isoquinoline alkaloids, and flavonoids of pharmacological value for their effect on cancer, bacterial, viral, and parasitic infection, inflammation, neurodegenerative diseases, diabetes, and skin ageing. Cytotoxic: The steroidal saponin methyl protoneogracillin isolated from Dioscorea collettii Hook. f. (order Dioscoreales, family Dioscoreaceae) inhibited the growth of human leukemic lymphoblast (CCRF-CEM), human colon carcinoma (KM12), human glial tumor (SF539), human glioblastoma (U251), human melanoma (M14), human kidney carcinoma (786-0), human prostate carcinoma (DU-145), and human breast carcinoma (MDA-MB-435) cells at very low doses.235 The anthraquinones 2-hydroxychrysophanol and rhein isolated from Hemerocallis fulva (L.) L. (order Asparagales, family Xanthorrhoeaceae) inhibited the proliferation of human breast, central nervous system, colon and lung cancer cells with IC50 values of 1.8–21.1 μg/mL.236 The isoquinoline alkaloid pancratistatin obtained from Pancratium littorale Jacq. (order Asparagales, family Amaryllidaceae) induced apoptosis selectively in cancer cells through a mechanism involving mitochondria.237 The carotenoid rhodoxanthin isolated from Potamogeton crispus L. (order Alismatales, family Potamogetonaceae) abrogated the survival of human epithelial cervical cancer (Hela) cells cultured in vitro.238 The alkaloid montanine isolated from Hippeastrum vittatum (L’Hér.) Herb. (order Asparagales, family Amaryllidaceae) inhibited the growth of human nonsmall cell lung carcinoma (H460) cells with an IC50 value of 0.5 μg/mL.239 Kaempferol-7O-beta-d-glucoside isolated from the rhizomes of Smilax china L (order Liliales, family Smilacaceae) induced G2/M phase growth arrest correlated with cyclin B1 and cdk1 decrease in a p53-independent manner and also induced apoptosis in human epithelial cervical cancer (Hela) cells cultured in vitro.240 The steroidal saponin asparanin A extracted from Asparagus officinalis L. (order Asparagales, family Asparagaceae) induced cell cycle arrest and triggered apoptosis in human hepatocellular liver carcinoma (HepG2) cells cultured in vitro.241 The steroidal saponin sieboldogenin extracted from Asparagus officinalis L. (order Asparagales, family Asparagaceae) induced cell cycle arrest and triggered apoptosis in human hepatocellular liver carcinoma (HepG2) cells cultured in vitro.241 The 2-alkylpyrrolidine alkaloid R-bgugaine isolated from the tubers of Arisarum vulgare Targ. Tozz. (order Alismatales, family Araceae) displayed cytotoxic activities against murine mastocytoma (P815) and human laryngeal carcinoma (Hep2) cells with IC50 values of 10 and 5 μg/mL, respectively.242 The homoisoflavonoid cambodianol isolated from the stems of Dracaena cambodiana Pierre ex Gagnep. (order Asparagales, family Asparagaceae) exhibited significant cytotoxic activities against human erythromyeloblastoid leukemia (K562) and human gastric cancer (SGC-7901) cells with an IC50 value of 1.4 μg/mL.243 Kaempferol-3-O-beta-d-glucopyranoside isolated from Iris pseudopumila Tin. (order Asparagales, family Iridaceae) exhibited antiproliferative effect against human amelanotic melanoma (C32) and human large lung carcinoma (CORL-23) cells cultured in vitro.244 The carotenoid crocin isolated from Crocus sativus L. (order Asparagales, family Iridaceae) protected rodent Dalton’s lymphoma infestation.245 The dihydrochalcone evelynin isolated from the rhizomes of Tacca chantrieri André (order Dioscoreales, family Taccaceae) negated the growth of human breast carcinoma (MDA-MB-435), human breast adenocarcinoma (MDA-MB-231B), human prostate cancer (PC-3), and human epithelial cervical cancer (Hela) cells with IC50 values of 4.1, 3.9, 4.7, and 6.3 μM, respectively.246 Antibacterial: The clerodane diterpenes bafoudiosbulbins A1 and B2 isolated from Dioscorea bulbifera L. (order Dioscoreales, family Dioscoreaceae) displayed antibacterial properties against Gram-negative Pseudomonas aeruginosa, Salmonella typhi, Salmonella paratyphi A, and Salmonella paratyphi B.247 A tirucallane-type triterpene isolated from Pandanus tectorius Soland. (order Pandanales, family Pandanaceae) inhibited the growth of Mycobacterium tuberculosis with a minimum inhibitory concentration of 64 μg/mL.248

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Antiviral: Phenanthrene derivatives isolated from Tamus communis L. (order Dioscoreales, family Dioscoreaceae) was antiviral against the vesicular stomatitis virus and human rhinovirus type 1B cultured in vitro.249,250 The isoquinoline alkaloid lycorine isolated from Lycoris radiata (L’Hér.) Herb. (order Asparagales, family Amaryllidaceae) inhibited the replication of the severe acute respiratory syndrome-associated coronavirus in vitro with an EC50 value of 15 nM.251 Parasiticidal: The steroidal saponin racemoside A extracted from the fruits of Asparagus racemosus Willd. (order Asparagales, family Asparagaceae) exhibited parasiticidal ­activity against Leishmania donovani with an IC50 value less than 2 μg/mL.252 The alkaloid 2-O-acetyllycorine isolated from Lycoris traubii W. Hayw. (order Liliales, family Amaryllidaceae) abrogated the survival of Trypanosoma brucei.253 The alkaloids ­hemanthamine, pseudolycorine, and ungeremine isolated from Phaedranassa dubia (Kunth) J.F.  Macbr. (order Asparagales, family Amaryllidaceae) exhibited parasiticidal properties against Plasmodium falciparum with IC50 values of 2.3, 0.8, and 0.3 μg/mL, respectively.254 Anti-inflammatory: The flavonoid irigenin isolated from Belamcanda chinensis (L.) DC. (order Asparagales, family Iridaceae) inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by murine macrophages (RAW264.7) cultured in vitro.255 The anthrone knipholone isolated from Kniphofia foliosa Hochst (order Asparagales, family Asphodelaceae) exhibited antimalarial, antitumor, and antioxidant properties, along with an inhibition of leukotriene formation in vitro.256 The steroidal saponin sieboldogenin obtained from the rhizomes of Smilax china L. (order Liliales, family Smilacaceae) inhibited the enzymatic activity of lipoxygenase with an IC50 of 38 μM and protected rodents in the carrageenan-induced paw edema experiment at a dose of 50 mg/kg.257 Central nervous system: The stilbene oxyresveratrol isolated from Smilax chinensis L. (order Liliales, family Smilacaceae) protected cultured rat cortical neurons against amyloid beta protein insults at a dose of 1–10 μM.258 The isoquinoline alkaloid galanthamine, which is common in members of the Liliaceae, is used as a drug to treat Alzheimer’s disease.259 Diabetes: 4-Hydroxybenzoic acid isolated from Pandanus odorus Ridl. (order Pandanales, family Pandanaceae) lowered the glycemia of normal rats.260 Cosmetics: The triterpene ruscogenin isolated from Ruscus aculeatus L. (order Asparagales, family Asparagaceae) inhibited the enzymatic activity of elastase with an IC50 value of 119.9 μM.261 The lignan cis-hinokiresinol isolated from Anemarrhena asphodeloides Bunge (order Asparagales, family Liliaceae) inhibited the enzymatic activity of hyaluronidase.262 The monoterpene crocusatin K isolated from the petals of Crocus sativus L. (order Asparagales, family Iridaceae) inhibited the enzymatic activity of tyrosinase with an IC50 value of 260 μM.263 The Liliales, Alismatales, and Asparagales are among the most interesting orders in the ­non-Commelinids group and are examined in detail in this chapter.

3.2.1  Order Asparagales Link, 1829 The order Asparagales consists of 14 families of flowering plants of which the Orchidaceae is ­discussed here. 3.2.1.1  Family Orchidaceae Juss., 1789, nom. cons., the Orchid Family The family Orchidaceae is a vast and successful clade consisting of 1000 genera and 20,000 species of orchids that are cosmopolitan. These peculiar plants are mycotrophic, terrestrial, or epiphytic and are known to produces stilbenes, phenanthrenes, and alkaloids of pharmacological interest. The stem base in epiphytic species is a pseudobulb. Terrestrial species grow from a rhizome, a corm, or a tuber. The leaves are simple, alternate, parallel-nerved, and often fleshy. The inflorescence is a raceme, a spike, or a panicle. The perianth consists of 3 sepals that are petaloid. The corolla

89

Superorder Lilianae Takht., 1967

c­ omprises 3 petals of which 2 are similar and 1 very different, often lobed and spurred, and bearing calli and processes of various shapes (labellum). OH OCH3

O Vanillin

H3CO HO

OCH3 OH HO

HO

Bulbophythrin A

O HO

OCH3 O Densiflorol B

HO

H3CO

OCH3 H3CO

OCH3

Erianin

The stamens and style are united into a column. The ovary is inferior, twisted, with a single cell, and contains numerous ovules. The fruits are capsular and dehiscent in 3 valves. The seeds are minute. A large number of ornamental plants belong to this family, especially from the genus Anguloa Ruiz & Pav., Brassia R. Br., Cattleya Lindl., Bulbophyllum Thouars, Catasetum Rich. ex Kunth, Cymbidium Sw., Dendrobium Sw., Epidendrum L., Laelia Lindl., Miltonia Lindl., Oncidium Sw., Phaius Lour., and Vanda R.Br. Examples of Orchidaceae are Vanilla planifolia Andrews, Vanilla tahitensis J.W. Moore, and Vanilla pompona Schiede that are the source of a well-known flavoring material: vanillin. Vanilla (British Pharmaceutical Codex, 1934) consists of the cured, fully grown, unripe fruit of Bourbon vanilla (Vanilla planifolia Andrews) or of Tahiti vanilla (Vanilla tahitensis J.W. Moore). It usually contains about 3% vanillin.

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Orchidaceae produce phenanthrenes of pharmacological interest. For instance, a phenanthrene isolated from Eulophia nuda Lindl. was remarkably cytotoxic against human breast adenocarcinoma (MCF-7) and human breast cancer (MDA-MB231) cells cultured in vitro.264 Two dimeric phenanthrenes bulbophythrins A and B isolated from Bulbophyllum odoratissimum (Sm.) Lindl. displayed significant cytocidal effect against cancer cells cultured in vitro. Bulbophythrin A abrogated the survival of human promyelocytic leukemia (HL-60) and human hepatocellular carcinoma (BEL-7402) cells cultured in vitro with IC50 values of 1.27 × 10−3 and 1.22 × 10−3 μmol/mL, respectively. Bulbophythrin B was most potent against human lung adenocarcinoma epithelial (A549) cells achieving an IC50 value of 1.18 × 10−3 μmol/mL.265 The phenanthrene densiflorol B isolated from Bulbophyllum odoratissimum (Sm.) Lindl. impaired the growth of human erythromyeloblastoid leukemia (K562), human promyelocytic leukemia (HL-60), human lung adenocarcinoma epithelial (A549), human hepatoma (BEL-7402), and human gastric cancer (SGC-7901) cells cultured in vitro.266 Other agents of pharmacological interest in the Orchidaceae are series of stilbenes. The stilbene erianin isolated from Dendrobium chrysotoxum Lindl. induced potent tumor necrosis, growth impairment, and quick vascular shutdown in hepatoma and melanoma experiments.267 Note that Orchidaceae are often traditionally used for its effect on inflammation, pain, and fever. The first plant discussed in this section is Acriopsis javanica Reinw. ex Blume. 3.2.1.1.1  Acriopsis javanica Reinw. ex Blume [From Greek akris = locust, and opsis = resemblance, and from Latin javanica = from Java] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië by Karl Ludwig von Blume in 1825. Blume (1796–1862) was deputy director of agriculture in Bogor. Common names: Aggrek darat, sakat bawang, sakat ubat kepialu (Malay). Habitat: This little epiphytic orchid grows wild on trees in the rainforests of Thailand, Malaysia, Indonesia, the Philippines, and Papua New Guinea. Diagnosis: The pseudobulbs of Acriopsis javanica Reinw. ex Blume are crowded, ovoid, and 2.5 cm long. The leaves are erect, light green, 2–3 per pseudobulbs, and 10 cm × 0.7 cm to 18 cm × 1 cm. The panicle is slender, grows up to a height of 15 cm, and displays numerous tiny flowers. The sepals are lanceolate, white, and crimson. The petals are spatulate, white, and present a crimson central bar. The side lobes of the lip are broad. The midlobe is lanceolate and blunt. The column is pink. The fruits are globose capsules with a diameter of 1.5 cm (Figure 3.44). Medicinal uses: In Malaysia, the plant is boiled in water to make a drink given to break fever. In Indonesia, the pseudobulbs are crushed and the juice extracted is dropped into the ears to stop tinnitus and to assuage earache. This plant is used to break fever and to lower blood pressure. Pharmacology: The pharmacological properties of members of the genus Acriopsis Bl. are apparently left insufficiently explored. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory agent(s). The next plant discussed in this section is Anoectochilus formosanus Hayata. 3.2.1.1.2  Anoectochilus formosanus Hayata [From the Greek anoectos = open, and cheilos = lip, and from Latin formosanus = from Formosa] History: This plant was first described in Icones Plantarum Formosanarum Nec non et Contributiones ad Floram Formosanam by Bunzō Hayata in 1914. Hayata (1874–1934) was a Japanese botanist.

Superorder Lilianae Takht., 1967

91

FIGURE 3.44  Acriopsis javanica Reinw. ex Blume. (From Det.: M.E. Mindernoud. Flora Malesiana. Date: 1982.)

Common names: Jewel orchid, tai wan yin xi an lan (Chinese), kim soan lian (Japanese). Habitat: This attractive orchid is terrestrial and found in the forests of Taiwan, Japan, Ryukyu Islands, and China. It is cultivated as an ornamental plant. Diagnosis: Anoectochilus formosanus Hayata is 25 cm tall. The stems are erect with 2–4 leaves. The leaves are purple below, dark green above, with white nerves. The blade is ovate, 2 cm × 1 cm to 5 cm × 3.5 cm, and acute at the apex. The inflorescence is a rusty velvety raceme. The flowers are resupinate, minute, and pale yellowish white. The ovary is twisted, fusiform, 1 cm long, and hairy. The sepals are reddish brown and hairy. The dorsal sepal is suborbicular, cymbiform, 0.5 cm in diameter, and acute at the apex. The lateral sepals are elliptical, 0.8 cm long, and acute at the apex. The petals are white, falcate, 0.8 cm long, and cuspidate at the apex. The lip is pale yellowish white, 1.5 cm long, Y-shaped, and laciniate. The hypochile is 0.2 cm long. The mesochile is 0.5 cm long. The epichile is longitudinally dilated and bilobed. The spur is conical and 0.4 cm long. The mouth is 0.3 cm in diameter. The column is ovoid and 0.2 cm long (Figure 3.45). Medicinal uses: In Taiwan, this plant is used to protect the liver, to prevent cancer, and to treat chest trouble, diabetes, heart diseases, and stomachache. In Malaysia, some species within the genus Anoectochilus Blume are used to treat tuberculosis. In China, the plant is used to break fever, to assuage pain, and to treat diseases of the lungs and liver, diabetes, tumors, and obesity. Constituents: The plant contains series of glycosides of which kinsenoside and corchoionoside C are probably antioxidant.268 Pharmacology: The antitumor, antidiabetic, hepatoprotective, anti-inflammatory, and hypolipidemic properties of Anoectochilus formosanus Hayata have been substantiated. An extract of the plant displayed a remarkable tumoricidal activity in rodents transplanted with murine colon carcinoma (CT-26) cells and protected human promyelocytic leukemia (HL-60) cells against H2O2-induced cellular damage on probable account of kinsenoside.269−271 Furthermore, an extract of the plant protected rodents against CCl4-induced hepatocellular ­damage on probable account of kinsenoside.272

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Medicinal Plants of China, Korea, and Japan

FIGURE 3.45  Anoectochilus formosanus Hayata.

O HO HO

OH O HO

O O Kinsenoside

Besides, an extract of the plant lowered glycemia, triglycerides, and cholesterol in streptozotocin-induced diabetic rodents likely because of kinsenoside.273,274 In an in vitro pharmacological study with 66 volunteers, an extract of the plant significantly abated the serum levels of cholesterol and low-density lipoprotein.275 In addition, an extract of the plant protected rodents against airway hyper-responsiveness in the ovalbumin aerosol experiment on probable account of kinsenoside.276,277 Moreover, an extract of the plant given orally to ovariectomized rodents (500 mg/kg) for 4 weeks inhibited bone weight loss and trabecular bone loss.278 One might be curious to look for antimycobacterial and cytotoxic agents in Anoectochilus ­formosanus Hayata. Bioresource: In vitro pharmacological study of kinsenoside for its effect on skin ageing. The next plant discussed in this section is Apostasia nuda R.Br. ex Wall. 3.2.1.1.3  Apostasia nuda R.Br. ex Wall. [From Greek apostasia = separation, and from Latin nuda = naked] History: This plant was first formally described in Plantae Asiaticae Rariores by Nathaniel Wallich in 1830. Wallich (1786–1854) was a Danish botanist. Common names: Pelampas budak, senjuan hutan jantan, kenching pelandok (Malay). Habitat: It is a terrestrial orchid found in the rainforests of Malaysia, India, and Indonesia. It is grown as an ornamental plant.

Superorder Lilianae Takht., 1967

93

FIGURE 3.46  Apostasia nuda R. Br. ex Wall. (From Det.: E.F. Voguel. Flora Malesiana. Date: December 1969.)

Diagnosis: The stems of Apostasia nuda R. Br. ex Wall. are slender, woody, ascending, and 60 cm long. The leaves are linear, acute, and 15 cm × 0.75 cm to 20 cm × 1.5 cm. The inflorescence is a terminal panicle that is decurved, 6–10 cm long, and displays numerous tiny flowers. The petals and sepals are white to yellowish, minute, lanceolate, and cuspidate (Figure 3.46). Medicinal uses: In Malaysia, this plant is used to to treat diarrhea and inflammation of the eyes. Pharmacology: The pharmacological properties of members of the genus Apostasia Bl. have apparently been left uncared for. Bioresource: Phytochemical and in vitro pharmacological studies and anti-inflammatory agent(s). The next plant discussed in this section is Bletilla striata (Thunb. ex Murray) Rchb. f. 3.2.1.1.4  Bletilla striata (Thunb. ex Murray) Rchb. f. [From Latin bletilla = little Bletia, the orchid genus Bletia Ruiz & Pav., and striata = striated] History: This plant was first formally described in Systemat Vegetabilium. Editio Decima Quarta of Carl Peter Thunberg in 1784. Thunberg (1743–1828) was a Swedish botanist. Common names: Chinese ground orchid, bai ji (Chinese), shiran (Japanese), ja ran (Korean). Basionym: Limodorum striatum Thunb. ex Murray. Habitat: It is a terrestrial orchid found in the forests of China, Japan, Korea, and Burma. is cultivated as an ornamental plant. Diagnosis: Bletilla striata (Thunb. ex Murray) Rchb. f. is 60 cm tall. The bulb is compressed and 3 cm in diameter. The stems are 25 cm tall, stout, and have 4–6 leaves. The leaves are widely spaced. The blade is elliptical and 8 cm × 1.5 cm to 30 cm × 4 cm. The base of the blade is contracted into an amplexicaul sheath and the apex is acute. The peduncle is 15–30 cm long, slender, and with a single sheathing bract. The rachis is flexuous, pendulous, 5 cm long, and has 3–10 flowers. The flowers are erect, purplish red, and showy. The sepals are purplish, narrowly oblong, and 3 cm × 0.8 cm. The lateral sepals are oblique and acute at the apex. The petals are purplish red, 3 cm × 1 cm, and acute at the apex. The lip

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FIGURE 3.47  Bletilla striata (Thunb. ex Murray) Rchb. f. (From Coll.: E.H. Wilson. Singapore Botanic Gardens. Orchidaceae Sinenses ex Herbario Amesiano. No. 1778. Loc.: China, Western Szechuan. Abundant on sandstone cliff. Alt.: 1000 feet. Date: June 1908.)

is white, tinged with purplish red veins, obovate-elliptical, 1.5 cm × 1 cm, and trilobed. The midlobe is square, 0.8 cm × 0.5 cm, crisped, and truncated. The column is subterete, 2 cm long, slender, dilated toward the apex, and winged. The rostrellum is large. The fruits are capsular and 3.5 cm long (Figure 3.47). Medicinal uses: In China, this plant is used to treat tuberculosis. It is applied on inflamed parts and cracked skin. The rhizomes are boiled in water to make a drink that is used to treat cough and indigestion. Constituents: The plant contains the anthraquinone physcion and the triterpene cyclobalanol.279 Pharmacology: Bletilla striata (Thunb. ex Murray) Rchb. f. contains some stilbenes that compromised the polymerization of tubulin into microtubules achieving an IC50 value of 10 μM.280 Physcion is probably responsible for the antitubercular property of the plant as it is known to inhibit mycobacterial detoxification enzyme mycothiol-S-conjugate amidase.281 Note that the plant contains series of antibacterial phenanthrenes.282 OH

O

H3C

OH

O O

CH3

Physcion

Bioresource: Phytochemical and in vitro pharmacological studies and anticancer stilbene(s). The next plant discussed in this section is Bromheadia finlaysoniana Rchb. f.

Superorder Lilianae Takht., 1967

95

3.2.1.1.5  Bromheadia finlaysoniana Rchb. f. [After Sir Edward French Bromhead (1789–1855), a British mathematician, and after Dr. George Finlayson (1790–1823), a Scottish naturalist] History: This plant was first formally described in Annales Botanices Systematicae by Heinrich Gustav Reichenbach in 1863. Reichenbach (1823–1889) was a German botanist. Common name: Finlayson’s Bromheadia. Habitat: It is a terrestrial orchid found in open dry places as well as in the rainforests of Thailand, Laos, Cambodia, Vietnam, Malaysia, Indonesia, New Guinea, and the Philippines. Diagnosis: Bromheadia finlaysoniana Rchb. f. is 2 m tall. The stems are basally sheathed with leaves. The inflorescence presents several floral bracts that are triangular, persistent, and 2-ranked. The rachis is elongated. The flowers are starry, showy, and white to creamcolored with a yellow lip with purple spots (Figure 3.48). Medicinal use: In Malaysia, the roots are boiled in water and the liquid obtained is drunk to treat rheumatism. Pharmacology: The pharmacological properties of members of the genus Bromheadia Lindl. are left uncared for. One might be curious to look for anti-inflammatory agents in Bromheadia finlaysoniana Rchb. Bioresource: Phytochemical and in vitro pharmacological studies and anti-inflammatory agent(s). The next plant discussed in this section is Bulbophyllum vaginatum (Lindl.) Rchb. f. 3.2.1.1.6  Bulbophyllum vaginatum (Lindl.) Rchb. f. [From Greek bulbo = bulb, and phullon = leaf, and from Latin vaginatum = sheathed]. History: This plant was first formally described in Annales Botanices Systematicae by Heinrich Gustav Reichenbach in 1864. Reichenbach (1823–1889) was a German botanist.

FIGURE 3.48  Bromheadia finlaysoniana Rchb. f. (From Coll. & Det.: S. Ahmad. Flora of Singapore. Singapore Botanic Gardens Herbarium. No. 325. Loc.: Singapore, Pulau Tekong. Date: February 2002.)

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FIGURE 3.49  Bulbophyllum vaginatum (Lindl.) Rchb. f. (From Coll.: P.T. Ong. Flora of Malaya. Forest Research Institute of Malaysia. Kepong, Malaysia. No. 64203. Loc.: Wayside, Gombak, Malaysia.)

Common name: Vagina Bulbophyllum. Habitat: This epiphytic orchid grows on trees in the rainforests of Malaysia and Indonesia. It is grown as an ornamental plant. Diagnosis: The rhizome of Bulbophyllum vaginatum (Lindl.) Rchb. f. is long and stout. The pseudobulbs are 3 cm apart, 3 cm long, and conical-ovoid. The leaves are solitary, fleshy, somewhat spongy, thick, elliptical, blunt, and 3 cm × 1.5 cm to 15 cm × 2.5 cm. The peduncle is 10 cm long with loose sheaths. The inflorescence is brush-like. The flowers are numerous, yellowish, showy, and grouped in a head. The upper sepal is ovate, blunt, ciliate at the margin, and 0.3 cm long. The lateral sepals are lanceolate, caudate, and 3 cm long. The petals are light yellow, tiny, ovate, blunt, and ciliate. The lip is lanceolate, acute, curved, and orange (Figure 3.49). Medicinal use: In Malaysia, the fruits are roasted and the juice obtained is dropped into the ears to treat earache. Pharmacology: The plant contains series of phenanthrene derivatives that would be worth testing for pharmacology.283,284 Bioresource: Anticancer agent(s). The next plant discussed in this section is Calanthe veratrifolia R.Br. 3.2.1.1.7  Calanthe veratrifolia R.Br. [From Greek kalos = beautiful, and anthos = flower, and from Latin veratrifolia = Veratrum-like leaves] History: This plant was first formally described in Botanical Register by Robert Brown in 1823. Brown (1773–1858) was a British botanist. Common names: San zhexia ji lan (Chinese), tsuru ran (Japanese). Habitat: It is a terrestrial orchid found in the forests of China, Taiwan, Bhutan, Cambodia, India, Indonesia, Japan, Laos, Malaysia, the Philippines, Sri Lanka, Vietnam, Australia, Madagascar, and Pacific islands. It is grown as an ornamental plant.

97

Superorder Lilianae Takht., 1967

FIGURE 3.50  Calanthe veratrifolia R. Br.

Diagnosis: The stems of Calanthe veratrifolia R.Br. are 3 cm long. The leaves are numerous, cuneate, 35 cm × 9 cm to 50 cm × 15 cm, and glossy. The petiole is 10–18 cm long. The scape is 60 cm long, hairy, and densely flowered. The flowers are yellowish and 2 cm long. The sepals are ovate. The petals are oblong. The lip is 3 cm long. The side lobes are linear. The midlobe presents a pair of oblong lobes. The spur is slender and clubbed (Figure 3.50). Medicinal uses: In Indonesia, the fresh leaves are chewed with betel nut and spices to treat diarrhea. The plant is applied to swellings and it is used to assuage toothache. Pharmacology: The pharmacological properties of Calanthe veratrifolia R.Br. are insufficiently explored. One could have noted that Calanthe arisanensis Hay. produces series of cytotoxic phenanthrene quinones including calanquinone A.285 OCH3 O

OCH3 O

OH

OCH3 Calanquinone A

Bioresource: In vitro pharmacological study of calanquinone A for its effect on cancer. The next plant discussed in this section is Cleisostoma birmanicum (Schltr.) Garay. 3.2.1.1.8  Cleisostoma birmanicum (Schltr.) Garay [From Greek kleistos = closed, and stoma = mouth, and from Latin Birmanicum = from Burma] History: This plant was first formally described in Notizblatt des Botanischen Gartens und Museums zu Berlin-Dahlem by Friedrich Richard Rudolf Schlechter in 1922. Schlechter (1872–1925) was a German botanist.

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Medicinal Plants of China, Korea, and Japan

Common name: Mei hua ge ju lan (Chinese). Basionym: Echioglossum birmanicum Schltr. Habitat: This little epiphytic orchid grows on trees in the rainforests of Burma, Malaysia, Thailand, Vietnam, and China. Diagnosis: The stems of Cleisostoma birmanicum (Schltr.) Garay are erect, elongate, 0.5 cm in diameter, with many leaves and verrucose roots. The leaves are narrowly lanceolate, 15 cm × 1.5 cm, thickly fleshy, obtuse, and unequally bilobed. The inflorescence is arching, longer than the leaves, branching, and displays innumerable tiny flowers. The flowers are fleshy. The sepals and petals are purplish. The lip is white. The dorsal sepal is elliptical, 1 cm × 0.5 cm, and obtuse. The lateral sepals are obliquely ovate, 1 cm × 0.5 cm, and obtuse. The petals are oblong, 1 cm × 0.4 cm, and obtuse. The spur is subconic, straight, 0.5 cm × 0.2 cm, and obtuse at the apex. Medicinal use: In Vietnam, this plant is used to treat orchitis. Pharmacology: The genus Cleisostoma Bl. is apparently insufficiently explored for pharmacology. One might be curious to look for antibacterial agents in Cleisostoma birmanicum (Schltr.). Bioresource: Phytochemical and pharmacological investigations and antibacterial agent(s). The next plant discussed in this section is Cremastra appendiculata (D. Don) Makino. 3.2.1.1.9  Cremastra appendiculata (D. Don) Makino [From Greek kremastra = pedicel, and from Latin appendiculata = having appendages] History: This plant was first formally described in Prodromus Florae Nepalensis by David Don in 1825. Don (1799–1841) was a Scottish botanist. Common names: Du juan lan (Chinese), yak nan cho (Korean). Basionym: Cymbidium appendiculatum D. Don. Habitat: It is a terrestrial orchid found in wet places in the forests of China, Taiwan, Bhutan, India, Japan, Korea, Nepal, Thailand, and Vietnam. It is grown as an ornamental plant. Diagnosis: Cremastra appendiculata (D. Don) Makino is 50 cm tall. The pseudobulb is ovoid and 3 cm in diameter. The leaves are solitary or in pairs. The blade is papery, broadly elliptical, 15 cm × 4 cm to 30 cm × 10 cm, with 3 nerves, cuneate at the base, and acute at the apex. The petiole-like base is 15 cm long. The inflorescence is 70 cm long. The rachis is 25 cm long and has 5–22 flowers. The flowers are fragrant, pendulous, nodding, pale purple, and campanulate. The lateral sepals are oblique. The petals are oblanceolate, 3 cm × 0.3 cm, and acuminate at the apex. The lip is linear, 3.5 cm × 0.5 cm, saccate at the base, and trilobed at the apex. The lateral lobes are linear, 5 cm × 0.1 cm, and obtuse at the apex. The midlobe is ovate, 0.8 cm × 0.5 cm, and acute at the apex. The fruits are capsular, pendulous, elliptical, and 3 cm × 1.5 cm (Figure 3.51). Medicinal uses: In China, this plant is used externally to heal boils, swellings, to remove freckles, and as an antidote to snakebites. In Japan, this plant is used to assuage toothache. Constituents: The plant produces militarine, loroglossin, protocatechuic acid, succinic acid, gastrodin, and daucosterol and series of phenanthrenes, as well as cirrhopetalanthin, ­flavanthrinin, and the pyrrolizidine alkaloid cremastrine.286−288 Pharmacology: Cremastra appendiculata (D. Don) Makino contains a homoisoflavanone that hampered the development of blood vessels in vitro and in vivo and inhibited UVBinduced skin inflammation through reduced cyclooxygenase-2 expression and nuclear factor-kappa B nuclear localization.289,290 Besides, the plant contains a chroman derivative that abrogated retinal neovascularization.291 In addition, the plant contains a lanostane triterpene that abrogated the survival of human breast adenocarcinoma (MCF-7) cells ­cultured in vitro achieving an IC50 value of 3.18 μM.292

99

Superorder Lilianae Takht., 1967

FIGURE 3.51  Cremastra appendiculata (D Don) Makino. (From Det.: I. Lund. Flora of the Sikkim Himalaya. Date: April 1986.) OH HO

O

OCH3

H3CO OH

O Homoisoflavanone

Bioresource: In vitro pharmacological study of homoisoflavone for its effect on skin ageing. The next plant discussed in this section is Cymbidium aloifolium (L.) Sw. 3.2.1.1.10  Cymbidium aloifolium (L.) Sw. [From Greek kymbes = boat-shaped, describing the shape of the lip, and from Latin aloifolium = with Aloe-like leaves] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Aloe-leafed Cymbidium, mengkuang munyet (Malay), wen ban lan (Chinese). Basionym: Epidendrum aloifolium L. Habitat: This epiphytic orchid naturally grows on trees in a geographical area covering China, Bangladesh, Cambodia, India, Indonesia, Laos, Malaysia, Burma, Nepal, Sri Lanka, Thailand, and Vietnam. It is grown as an ornamental plant. Diagnosis: The pseudobulbs of Cymbidium aloifolium (L.) Sw. are ovoid, flattened, 4 cm in diameter, and enclosed in leaf bases. The leaves are oblong, 40 cm × 1.5 cm to 90 cm × 5 cm, thickly leathery, fleshy, and round at the apex. The inflorescence arises from within sheaths at the base of the pseudobulb. The inflorescence is pendulous, orangish, and 60 cm long. The

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FIGURE 3.52  Cymbidium aloifolium (L.) Sw. (From Coll.: G. Umbai for A.H. Millard. Phyto-chemical Survey of the Federation of Malaya. No. 1861. Loc.: Ulu Langat, Selangor, Malaysia. Date: November 25, 1959.)

rachis has many flowers and is pendulous. The flowers are slightly fragrant. The sepals and petals are pale yellow with broad central brown stripes. The sepals are oblong, 1.5 cm × 0.5 cm, and obtuse at the apex. The petals are elliptical, 1.8 cm × 0.5 cm, and obtuse at the apex. The lip is ovate, 2 cm long, saccate at the base, and trilobed. The lateral lobes are acute. The midlobe is recurved. The fruits are capsular, irritant, elliptical, and 6 cm × 3 cm (Figure 3.52). Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used to bathe children who are sick, to regulate menses, and to heal cuts, wounds, and burns. Constituents: Cymbidium aloifolium (L.) Sw. contains the phenanthrene quinone cymbinodin A as well as aloifol I, aloifol II, 6-O-methykoelonin, batatasin III, coelonin, and gigantol.293,294 Pharmacology: One could infer that the healing property of the plant involves anti-inflammatory stilbenes. One such compound is gigantol isolated from Cymbidium goeringii (Rchb. f.) Rchb. f., that abrogated the generation of nitric oxide and prostaglandin E2 by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.295

H3CO OH

O HO O

OH

OCH3



Cymbinodin A



Gigantol

OCH3

Bioresource: In vitro pharmacological study of gigantol for its effect on neurodegeneration. The next plant discussed in this section is Cymbidium ensifolium (L.) Sw.

Superorder Lilianae Takht., 1967

101

3.2.1.1.11  Cymbidium ensifolium (L.) Sw. [From Greek kymbes = boat-shaped, describing the shape of the lip, and ensifolium = with swordshaped leaves] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Jian lan (Chinese), so ran (Korean). Basionym: Epidendrum ensifolium L. Habitat: This terrestrial orchid is found in the forests of China, Taiwan, Cambodia, India, Indonesia, Japan, Laos, Malaysia, Papua New Guinea, the Philippines, Sri Lanka, Thailand, and Vietnam. It is grown as an ornamental plant. Diagnosis: The pseudobulbs of Cymbidium ensifolium (L.) Sw. are ovoid, 2.5 × 1.5 cm, and enclosed in leaf bases. The leaves are sword-shaped and 30 cm × 1 cm. The inflorescence is erect, 35 cm tall, and emerges from the base of the pseudobulbs. The rachis has 3–9 flowers. The flowers are fragrant, showy, pale yellowish green, and spotted purple. The midlobe shows a few red spots. The sepals are oblong, 2.5 cm × 0.5 cm, and acute at the apex. The lateral sepals are oblique. The petals are 1.5 cm × 0.5 cm and acute at the apex. The lip is ovate, 1.5 cm long, and obscurely trilobed. The lateral lobes are erect. The midlobe is recurved, ovate, and 1.2 cm wide. The fruits are capsular, elliptical, and 5 cm × 2 cm (Figure 3.53). Medicinal uses: In China, the pseudobulbs are used to assuage stomachache and to treat venereal diseases. In Cambodia, Laos, and Vietnam, the flowers are used to wash the eyes, the leaves are used to excite the discharge of urine, and the roots are used to cure chest trouble. Pharmacology: The diuretic property of the plant is not validated yet, but note that cymbidine A, a monomeric peptidoglycan, extracted from Cymbidium goeringii (Rchb. f.) Rchb. f. exhibited hypotensive and diuretic activities.296 Besides, the stilbene gigantol isolated from Cymbidium goeringii (Rchb. f.) Rchb. f. abrogated the generation of nitric oxide and

FIGURE 3.53  Cymbidium ensifolium (L.) Sw.

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Medicinal Plants of China, Korea, and Japan

p­ rostaglandin E2 by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.295 Cymbidium ensifolium (L.) Sw. contains series of phenanthrenes that would be worth studying for pharmacology.297 Bioresource: Phytochemical and pharmacological investigations and diuretic agent(s). The next plant discussed in this section is Dendrobium blumii Lindl. 3.2.1.1.12  Dendrobium blumii Lindl. [From Greek dendron = tree, and cheilos = lip, and after Karl Ludwig von Blume (1796–1862), German botanist director of the Rijksherbarium] History: This plant was first formally described in The Genera and Species of Orchidaceous Plants by John Lindley in 1830. Lindley (1799–1865) was a British botanist. Common name: Blume’s Dendrobium. Habitat: This epiphytic orchid grows on trees in the rainforests of Malaysia and Indonesia. Diagnosis: The stems of Dendrobium blumii Lindl. are 40 cm long and red. The pseudobulbs are 4.5 cm × 3 cm. The leaves are few, ovate, bifid, and 3 cm × 2.25 cm. The sheath is 3 cm long. The flowers are white, solitary, and 1.5 cm long. The upper sepal is lanceolate and acute. The laterals sepals are triangular and acute. The petals are lanceolate, acute, and whitish crimson. The side lobes of the lip are round, white-nerved, and violet. The midlobe is lanceolate and acute. Medicinal uses: In Malaysia, this plant is reduced into a paste that is smeared on itches and allergies. Pharmacology: One could reasonably anticipate the role of some anti-inflammatory phenanthrene or stilbene derivatives in the medicinal uses of this plant. Bioresource: Phytochemical and pharmacological investigations and anticancer agent(s). The next plant discussed in this section is Dendrobium crumenatum Sw. 3.2.1.1.13  Dendrobium crumenatum Sw. [From Greek dendron = tree, and bios = life and crumenatum = unknown origin] History: This plant was first formally described in Journal für die Botanik by Olof Peter Swartz in 1799. Swartz (1760–1818) was a Swedish botanist. Common names: Pigeon orchid, sparrow orchid, dove orchid, poko merpati, bunga angin (Malay), mu shi hu (Chinese). Basionym: Dendrobium kwashotense Hayata. Habitat: This epiphytic orchid grows on trees in a geographical area covering Taiwan, Cambodia, India, Andaman islands, Indonesia, Laos, Malaysia, Burma, the Philippines, Sri Lanka, Thailand, and Vietnam. It is grown as an ornamental plant. Diagnosis: The stems of Dendrobium crumenatum Sw. are 1 m long. The pseudobulbs are elliptical, grooved, and 9 cm × 2.5 cm. The leaves are elliptical, coriaceous, blunt, and 9 cm × 3 cm. The sheaths are 4.5 cm long. The flowers are pure white. The upper sepal is 2.5 cm long, lanceolate, acute, and 2.5 cm long. The fruits are capsular, 2.2 cm long, and elliptical (Figure 3.54). Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used to remove impurities from the blood. In Malaysia, the plant is used to heal boils and the juice extracted from the pseudobulbs is used to assuage earache.

Superorder Lilianae Takht., 1967

103

FIGURE 3.54  Dendrobium crumenatum (L.) Sw. (From Det.: S. Ahmad. Flora of Singapore. Singapore Botanic Gardens. No. GAT171. Loc.: Singapore, Pulau Ubin, Chek Jawa. Date: January 14, 2003.)

Pharmacology: Apparently insufficiently explored. One could reasonably anticipate the role of some anti-inflammatory phenanthrene or stilbene derivatives in the healing and analgesic properties of this plant. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory agent(s). The next plant discussed in this section is Dendrobium moniliforme (L.) Sw. 3.2.1.1.14  Dendrobium moniliforme (L.) Sw. [From Greek dendron = tree, and bios = life, and from Latin monoliformis = necklace-shaped] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Necklace-shaped Dendrobium, xi jing shi hu (Chinese), chosei ran (Japanese), seok gok (Korean). Basionym: Epidendrum moniliforme L. Synonyms: Callista moniliforme (L.) Kuntze, Dendrobium castum Bateman ex Rchb. f., Dendrobium catenatum Lindl., Dendrobium crispulum Kimura & Migo, Dendrobium heishanense Hayata, Dendrobium kosepangii C.L. Tso, Dendrobium monile (Thunb.) Kraenzl., Dendrobium moniliforme var. taiwanianum S.S. Ying, Dendrobium nienkui C.L. Tso, Dendrobium tosaense var. chingshuishanianum S.S. Ying, Dendrobium yunnanense Finet, Dendrobium zonatum Rolfe, Epidendrum monile Thunb. Habitat: This epiphytic orchid grows on trees in the forests of China, Taiwan, Bhutan, India, Japan, Korea, Burma, Nepal, and Vietnam. It is cultivated as an ornamental plant. Diagnosis: The stems of Dendrobium moniliforme (L.) Sw. are erect, fleshy, stout, cylindrical, and 30 cm long. The internodes are 2.5 cm long and golden yellow. The leaves are alternate, lanceolate or elliptical, 3 cm × 0.5 cm to 5 cm × 1.2 cm, decurrent at the base, and obtuse at the apex. The inflorescence has 1–3 flowers. The flowers are fragrant, showy, and pure white. The sepals and petals are similar, lanceolate, 4 cm × 1 cm, and acute at the

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FIGURE 3.55  Dendrobium moniliforme (L.) Sw.

apex. The lateral sepals are oblique. The petals are elliptical and acute, with 5 or 6 nerves. The lip is ovate, cuneate at the base, and trilobed. The lateral lobes are round and erect. The midlobe is ovate, glabrous, and acute at the apex (Figure 3.55). Medicinal uses: In China, this plant is used to cure fatigue, impotence, and arthritis, and it is given as a nutrient to convalescent people. Pharmacology: The anti-inflammatory property of Dendrobium moniliforme (L.) Sw. involves probably series of phenanthrene quinones of which denbinobin exhibited antiinflammatory and proapoptotic properties.298,299 In addition, the plant is known to produce sesquiterpenes, the pharmacological property of which remains unknown.300,301 One might be curious to study the dietetic value of this plant. O

H3CO O

HO

OCH3

Denbinobin

Bioresource: In vitro pharmacological study of denbinobin for its effect on cancer. The next plant discussed in this section is Dendrobium nobile Lindl. 3.2.1.1.15  Dendrobium nobile Lindl. [From Greek dendron = tree, and bios = life, and from Latin nobile = notable] History: This plant was first formally described in The Genera and Species of Orchidaceous Plants by John Lindley in 1830. Lindley (1799–1865) was a British botanist.

Superorder Lilianae Takht., 1967

105

Common names: Noble Dendrobium, shi hu (Chinese). Synonyms: Dendrobium formosanum (Rchb. f.) Masam., Dendrobium nobile var. formosanum Rchb. f., Dendrobium nobile var. nobilus Burb. Habitat: This epiphytic orchid grows on trees in the forests of China, Taiwan, Bhutan, India, Laos, Burma, Nepal, Thailand, and Vietnam. It is also cultivated as an ornamental plant. Diagnosis: The stems of Dendrobium nobile Lindl. are erect, cylindrical, 10–60 cm long, stout, articulate, and fleshy. The leaves are oblong, 6 cm × 1 cm to 10 cm × 3 cm, leathery, fleshy, and obtuse at the apex. The inflorescence is cauliflorous, 5 cm long, and has 1–4 flowers. The flowers are showy, white, and purplish at the apex. The dorsal sepal has 5 nerves and is oblong, 3.5 cm × 1.5 cm, and obtuse at the apex. The lateral sepals have 5 nerves, and are oblique at the base and acute at the apex. The petals have 3 nerves and are ovate, 3.5 cm × 2.5 cm, and obtuse at the apex. The lip is ovate, 3.5 cm long, hairy, and obtuse at the apex. The column is 0.5 cm long (Figure 3.56). Medicinal uses: In China, Laos, and Vietnam, this plant is used to treat indigestion, to break fever, and to stimulate the secretion of saliva. It is also used as a mild analgesic and to reduce blood pressure. Pharmacology: Dendrobium nobile Lindl. contains series of phenanthrenes of which lusianthridin and denbinobin are cytotoxic against human lung adenocarcinoma epithelial (A549), human ovary adenocarcinoma (SK-OV-3), and human promyelocytic leukemia (HL-60) cells cultured in vitro.302,303 The anti-inflammatory property of the plant is owed to erianthridin, ephemeranthol A, coelonin, epheneranthol C, and lusianthridin that inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides with IC50 values of 9.6–19.5 μM.304

FIGURE 3.56  Dendrobium nobile Lindl.

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Medicinal Plants of China, Korea, and Japan

HO

HO

OCH3

OH H3CO

HO Lusianthridin



OCH3

Erianthridin



H N H

CH3

OCH3 OH

H H3CO

O O H3C



CH3

OCH3

HO

Dendrobine

Moscatilin

OH

HO HO

O OH

H3C

OH

H

HH

OH

H H H3C

O HO

O

O

OH OH

Sesquiterpene glycoside of Dendrobium

A substance called SG-168 isolated from the plant protected rat pheochromocytoma (PC12) cells against H2O2 damages.305 In addition, bibenzyl derivatives, nobilin D and nobilin E, extracted from the plant showed remarkable antioxidant effects in the 2,2-diphenyl-1-picrylhydrazyl experiment.306 The plant contains dendroflorin that inhibited the senescence of human aborted fetal (MRC-5) cells cultured in vitro.307 Dendrobium nobile Lindl. produces series of alloaromadendrane, emmotin, and picrotoxane sesquiterpene glycosides with immunomodulatory activity including dendroside A and dendronobilosides A and B.308,309 Finally, the stilbene moscatilin isolated from the plant protected the Gram-negative Salmonella typhimurium against a broad array of mutagenic chemicals.310 The plant probably contains the neurotoxic sesquiterpene alkaloid dendrobine. Bioresource: In vitro pharmacological study of lusianthridin for its effect on cancer. The next plant discussed in this section is Dendrobium pumilum Sw. 3.2.1.1.16  Dendrobium pumilum Sw. [From Greek dendron = tree, and bios = live, and from Latin pumilum = dwarf] History: This plant was first formally described in Neues Journal für die Botanik by Olof Peter Swartz in 1805. Swartz (1760–1818) was a Swedish botanist.

Superorder Lilianae Takht., 1967

107

Common name: Sakat kalumbai (Malay). Synonyms: Bulbophyllum pumilum (Sw.) Lindl., Genyorchis pumila (Sw.) Schltr. Habitat: This dwarfish epiphytic orchid grows on trees in the rainforests of Malaysia, Burma, and Indonesia. Diagnosis: The pseudobulbs of Dendrobium pumilum Sw. are tufted, cylindrical, 5 cm long, and yellow. The leaves are fleshy, arranged in pairs, elliptical, and 4 × 1.5 cm. The flowers are solitary, membranaceous, fragile, and ephemeral. The upper sepal is lanceolate. The lateral sepals are ovate. The petals are linear and present reddish nervations. The lip is oblong, entire, and yellow with red nervations. Medicinal use: In Malaysia, this plant is used to cure dropsy. Pharmacology: Apparently unknown. Bioresource: Phytochemical and pharmacological investigations of diuretic agent(s). The next plant discussed in this section is Dendrobium subulatum (Blume) Lindl. 3.2.1.1.17  Dendrobium subulatum (Blume) Lindl. [From Greek dendron = tree, and bios = life, and from Latin subula = awl] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië by Karl Ludwig von Blume in 1825. Blume (1796–1862) was deputy director of agriculture in Bogor. Common name: Terete Dendrobium. Basionym: Onychium subulatum Bl. Habitat: This tiny epiphytic orchid grows on trees in the rainforests of Malaysia and Indonesia. Diagnosis: The stems of Dendrobium subulatum (Blume) Lindl. are tufted, numerous, 20 cm long, and slender. The leaves are narrow, flattened, recurved, and 1.5 cm long. The sheaths are minute. The flowers are solitary and axillary, membranaceous, and 1.5 cm long. The upper sepals are small, lanceolate, and blunt. The lateral sepals are triangular and acute. The petals are linear. The lip is oblong, truncate, shortly trilobed, and yellowish white (Figure 3.57).

FIGURE 3.57  Dendrobium subulatum (Blume) Lindl.

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Medicinal Plants of China, Korea, and Japan

Medicinal use: In Malaysia, this plant is used to mitigate headache. Pharmacology: Apparently unknown. Bioresource: Phytochemical and pharmacological investigations and analgesic or hypotensive agent(s). The next plant discussed in this section is Epipactis mairei Schltr. 3.2.1.1.18  Epipactis mairei Schltr. [From Greek epipegnuo = coagulate milk, and after the French botanist Edouard Ernest Maire (1848–1932)] History: This plant was first formally described in Repertorium Specierum Novarum Regni Vegetabilis, Beihefte of Friedrich Richard Rudolf Schlechter in 1919. Schlechter (1872– 1925) was a German botanist. Common names: Maire’s Epipactis, da ye huo shao lan (Chinese). Habitat: It is a rare terrestrial orchid found in the grasslands of China, Bhutan, Burma, and Nepal. Diagnosis: Epipactis mairei Schltr. is 1 m tall. The rhizome is short. The stems are glabrous at the base and rusty hairy at the apex. The leaves are elliptical or lanceolate, 7 cm × 3 cm to 16 cm × 8 cm, scabrous, amplexicaul at the base, and shortly acuminate at the apex. The rachis is 20 cm long, rusty hairy, and densely flowered. The flowers are nodding and resupinate. The sepals and petals are yellowish green tinged purple. The lip shows a purplish brown hypochile and an orangish epichile. The dorsal sepal is elliptical, cymbiform, 1.5 cm × 0.75 cm, and acuminate at the apex. The lateral sepals are ovate, oblique, 1.5 cm × 0.5 cm, and acuminate at the apex. The petals are elliptical, 1 cm long, and acuminate at the apex. The lip is 1.5 cm long. The hypochile is cymbiform and 0.9 cm long. The epichile is thickened, ovate, 0.5 cm × 0.3 cm, and acute at the apex. The fruits are capsular, elliptical, 0.2 cm long, and glabrous (Figure 3.58). Medicinal uses: In China, this plant is reduced into a paste that is applied to burns and scalds. The fruits are boiled in water and the liquid is drunk to invigorate, to stimulate hormone secretion, and to dye the hair.

FIGURE 3.58  Epipactis mairei Schltr.

109

Superorder Lilianae Takht., 1967

Pharmacology: The pharmacology of members of the genus Epipactis Zinn is left unstudied. One might be curious to look for nootropic agents in Epipactis mairei Schltr. Bioresource: Phytochemical and pharmacological investigations and cosmetology. The next plant discussed in this section is Eria pannea Lindl. 3.2.1.1.19  Eria pannea Lindl. [From Latin erio = woolliness, and pannea = cloth] History: This plant was first formally described in Plantae Asiaticae Rariores by John Lindley in 1828. Lindley (1799–1865) was a British botanist. Common name: Kura kubong (Malay). Habitat: This little epiphytic orchid grows on trees in the rainforests of Malaysia, Borneo, Burma, India, and Himalayas. Diagnosis: The leaves of Eria pannea Lindl. are arranged in groups of 3, linear, curved, acuminate, fleshy, terete, dark green, and 5–20 cm long. The inflorescence arises from the axil of an upper leaf and is 3 cm long and whitish woolly. The flowers are fragrant, small, and arranged in groups of 3. The upper sepal is lanceolate and acute. The lateral sepals are 1.5 cm long, ochre, and whitish woolly on the outside. The petals are lanceolate and dark yellow on the inside. The lip is entire, oblong, acute, fleshy, purple, and yellow (Figure 3.59). Medicinal uses: In Malaysia, this plant is used to break malarial fever. In India, it is used to soothe inflammation of the skin. Pharmacology: Apparently unknown. Eria carinata Gibson, Eria stricta Lindl., and Eria confusa Hook. f. produce series of phenanthrenes such as nudol.311,312 Eria flava Griff. produces stilbenes and coelonin.313

HO

OH

Coelonin

OH

H3CO

H3CO



HO



OCH3

Nudol

FIGURE 3.59  Eria pannea Lindl. (From Flora of Indonesia. Herbarium Bogoriense and the Harnold Arboretum of Harvard University. Loc.: Indonesia, Kalimantan. Sintang HPH 70 km, west of camp, off main road; along a new log and surrounding environs toward 71 km, 0°51′54′N–112°13′30′. Alt.: 150 m.)

110

Medicinal Plants of China, Korea, and Japan

Note that coelonin isolated from Dendrobium nobile Lindl. inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.304 Is coelonin involved in the anti-inflammatory property of Eria pannea Lindl.? Bioresource: In vitro pharmacological study of nudol for its effect on neurodegeneration. The next plant discussed in this section is Geodorum nutans (C. Presl) Ames. 3.2.1.1.20  Geodorum nutans (C. Presl) Ames [From Greek geo = earth, and doron = gift, and from Latin nutans = nodding or drooping] History: This plant was first formally described in Reliquiae Haenkeanae by Karel Boriwog Presl in 1827. Presl (1794–1852) was a Czechoslovakian botanist. Common name: Di bao lan (Chinese). Basionym: Dendrobium nutans C. Presl. Habitat: It is a rare terrestrial orchid found in the Philippines, Indonesia, and Hong Kong. Diagnosis: The rhizome Geodorum nutans (C. Presl) Ames is tuberous. The stem is 70 cm tall. The leaves are large, elliptical, 35 cm × 7 cm, plicate, cuneate at the base, and acute at the apex. The scapes are 50 cm tall. The racemes are nodding and about 3 cm long. The flowers are purplish and 1 cm long. The lip is retuse. The fruits are capsular, nodding, and 3.5 cm long (Figure 3.60). Medicinal uses: In the Philippines, the bulbs are crushed and the paste obtained is applied to boils and festering abscesses. Pharmacology: The pharmacological properties of members of the genus Geodorum Jacks. are apparently left insufficiently explored. One might be curious to look for antibacterial agents in Geodorum nutans (C. Presl) Ames. Bioresource: Phytochemical and pharmacological investigations and antibacterial agent(s). The next plant discussed in this section is Goodyera repens (L.) R.Br.

FIGURE 3.60  Geodorum nutans (C. Presl) Ame. (From Coll.: M.S. Clemens. Herbarium. University of California. Plants of the Philippines. No. 18255. Loc.: Philippine, San Fernando, Pampanga Province, Luzon. Date: July 1928.)

111

Superorder Lilianae Takht., 1967

3.2.1.1.21  Goodyera repens (L.) R.Br. [After John Goodyer (1592–1664), an English plant collector and botanist, and from Latin repens = having creeping and rooting stems] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Creeping ladies tresses, dwarf rattlesnake plantain, xiao ban ye lan (Chinese), ae gi sa cheol ran (Korean). Basionym: Satyrium repens L. Synonyms: Goodyera repens var. ophioides Fernald, Peramium ophioides (Fernald) Rydb. Habitat: It is a little terrestrial orchid found in the forests and bogs of China, Taiwan, Bhutan, India (specifically Kashmir), Japan, Korea, Burma, Nepal, Russia, Europe, and North America. Diagnosis: Goodyera repens (L.) R.Br. is 25 cm tall. The rhizome is slender. The stems are ascending, 5 cm long, and have 4–6 leaves. The leaves are rosulate at the base of the stems, marked with white nervation, ovate, 3 cm × 1.5 cm, and acute at the apex. The base of the blade is cuneate and forms a tubular sheath that is 1–1.5 cm long. The rachis is 5 cm long and has 5–20 flowers. The flowers are white, minute, and spirally arranged. The sepals are hairy and have 1 nerve. The dorsal sepal is ovate, 0.4 cm × 0.1 cm, and obtuse at the apex. The lateral sepals are ovate, oblique, 0.4 cm × 0.25 cm, and obtuse at the apex. The petals are spatulate, oblique, 0.3 cm × 0.1 cm, obtuse at the apex, and have 1 nerve. The lip is ovate and 0.3 cm × 0.2 cm. The hypochile is concave and papillose on the inside. The ­epichile is ligulate, 0.1 cm long, and slightly recurved (Figure 3.61). Medicinal use: In Taiwan, this plant is used to break fever. Pharmacology: Apparently insufficiently explored. Members of the genus Goodyera R.Br. are known to contain kinsenoside, goodyeroside A, and goodyerin. An extract of Goodyera sp. protected rodents against CCl4-induced hepatocellular damage.314

OCH3 HO

OH OH

H3CO O

HO

O OH

O CH3

OH O

O OH

HO

O

HO

OH OH



OH

OH

Goodyerin

O

O

O OH



CH3

O

Goodyeroside A

Goodyerin isolated from Goodyera species exhibited a remarkable and dose-dependent sedative and anticonvulsant effects in rodents.314 One might be curious to look for anti-inflammatory agents in this plant.

112

Medicinal Plants of China, Korea, and Japan

FIGURE 3.61  Goodyera repens (L.) R.Br.

Bioresource: In vitro pharmacological study of goodyeroside A for its effect on skin ageing and of goodyerin for its effect on epilepsy. The next plant discussed in this section is Goodyera schlechtendaliana Rchb. f. 3.2.1.1.22  Goodyera schlechtendaliana Rchb. f. [After John Goodyer (1592–1664), an English plant collector and botanist, and after Diederich von Schlechtendal (1794–1866), a German botanist] History: This plant was first formally described in Linnaea by Heinrich Gustav Reichenbach in 1849. Reichenbach (1823–1889) was a German botanist. Common names: Schlechtendal’s Goodyera, ban ye lan (Chinese), miyamauzura (Japanese), sa cheol ran (Korean). Habitat: It is a little terrestrial orchid found in the forests of China, Taiwan, Bhutan, India, Indonesia, Japan, Korea, Nepal, Thailand, and Vietnam. It is cultivated as an ornamental plant. Diagnosis: Goodyera schlechtendaliana Rchb. f. grows to a height of 20 cm. The rhizome is slender. The stems are erect, fleshy, pinkish, 5 cm long, and have 4–6 leaves. The leaves are lanceolate, 2.5 cm × 1 cm, pale green below, dark green above with irregular white markings, and acute at the apex. The base of the blade forms a tubular sheath that is 1.8 cm long. The rachis is 10 cm long and densely flowered. The flowers are white, tinged with pink, and small. The sepals are hairy on the outer surface and have 1 nerve. The dorsal sepal is narrowly elliptical-lanceolate, cymbiform, 1 cm × 0.3 cm, and acute at the apex. The lateral sepals are lanceolate, 0.7 cm × 0.3 cm, and acute at the apex. The petals are rhombic, 1 cm × 0.3 cm, obtuse at the apex, and have 1 nerve. The lip is ovate and 0.8 cm × 0.4 cm. The hypochile is concave and papillose. The epichile is ligulate, 0.3 cm long, and slightly recurved. The rostrellum is 0.3 cm long and deeply bifid (Figure 3.62). Medicinal use: In China, this plant is used to treat bone injury. Constituents: Goodyera schlechtendaliana Rchb. f. contains goodyerin, rutin, kaempferol-3O-rutinoside, and isorhamnetin-3-O-rutinoside, as well as a glycosides.315−317

Superorder Lilianae Takht., 1967

113

FIGURE 3.62  Goodyera schlechtendaliana Rchb. f.

Pharmacology: The medicinal property of Goodyera schlechtendaliana Rchb. f. could be mediated by rutin that displayed anti-inflammatory activity in the carrageenan-induced paw edema experiment.318 Bioresource: In vitro pharmacological study of rutin for its effect on inflammation. The next plant discussed in this section is Habenaria dentata (Sw.) Schltr. 3.2.1.1.23  Habenaria dentata (Sw.) Schltr. [From Greek habena = straps, reins for the long, slender lateral lobes of the lip, and from Latin ­dentata = toothed-like a saw] History: This plant was first formally described in Kongl. Vetenskaps Academiens Handlingar by Olof Peter Swartz in 1800. Swartz (1760–1818) was a Swedish botanist. Common names: Mao yu feng hua (Chinese), dai sagi so (Japanese). Basionym: Orchis dentata Sw. Habitat: It is a terrestrial orchid found in the forests on slopes or along valleys in a geographical area comprising China, Taiwan, Cambodia, India, Japan, Laos, Burma, Nepal, Thailand, and Vietnam. It is cultivated as an ornamental plant. Diagnosis: Habenaria dentata (Sw.) Schltr. is 80 cm tall. The tuber is oblong, 5 cm × 3 cm, and fleshy. The stems are erect, terete, and stout. The blade is oblong, 15 cm × 5 cm, elliptical, amplexicaul at the base, and acute at the apex. The raceme is densely flowered and 15 cm long. The flowers are pure white. The sepals and petals are ciliate. The dorsal sepal has 5 nerves and is broadly ovate, concave, 1 cm × 0.7 cm, and acute at the apex. The lateral sepals have 5 nerves and are reflexed, obliquely ovate, 1.5 cm long, and acute at the apex. The petals are falcate, 1 cm × 0.25 cm, and present a pair of nerves. The lip is obovate, 2 cm × 1.5 cm, and trilobed. The lateral lobes are rhombic, 0.8 cm wide, and ­serrate. The midlobe is linear, 0.5 cm × 0.15 cm, obtuse at the apex, and has 3 nerves. The spur is pendulous, cylindrical, and 4 cm long (Figure 3.63).

114

Medicinal Plants of China, Korea, and Japan

FIGURE 3.63  Habenaria dentata (Sw.) Schltr. (From Flora of China. National University of Peking. Loc.: Chekiang, China. Date: September 25, 1910.)

Medicinal use: In China, the tubers are used to treat colic. In Taiwan, a paste of this plant is applied to swellings and wounds. Pharmacology: Apparently insufficiently explored. Habenariol isolated from Habenaria repens Nutt. protected human high-density lipoprotein against copper-induced lipid peroxidation.319 One could reasonably think that habenariol is involved in the anti-inflammatory use of Habenaria dentata (Sw.) Schltr. OH

O O HO

O HO

O H3C

CH3

Habenariol

Bioresource: In vitro pharmacological study of habenariol for its effect on skin ageing. The next plant discussed in this section is Hetaeria obliqua Blume. 3.2.1.1.24  Hetaeria obliqua Blume [From Greek hetaeria = female companion, and from Latin obliqua = oblique] History: This plant was first formally described in Collection des Orchidées by Karl Ludwig von Blume in 1858. Blume (1796–1862) was deputy director of agriculture in Bogor. Common names: Poko tumbak hutan (Malay), xie ban fan chun lan (Chinese). Habitat: This terrestrial orchid is found in the forests of Indonesia, Malaysia, and Thailand.

Superorder Lilianae Takht., 1967

115

FIGURE 3.64  Hetaeria obliqua Blume.

Diagnosis: Hetaeria obliqua Blume is 30 cm tall. The stems are creeping and stout. The leaves are 6 cm × 2 cm to 9 cm × 3 cm, oblique, lanceolate, dark green, and present a silver bar. The petiole is 1.5–3 cm long. The scape is slender and hairy. The spike is 30 cm tall. The flowers are numerous, tiny, and reversed. The upper sepal is 0.75 cm long, connate, and white. The lateral sepals are hairy, lanceolate, blunt, and dull red. The lip is white and minute. The fruits are capsular, elliptical, sessile, and 1 cm long (Figure 3.64). Medicinal use: In Malaysia, this plant is used to heal sores. Pharmacology: The pharmacology of the genus Hetaeria Bl. has been left insufficiently explored for. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory agent(s). The next plant discussed in this section is Hippeophyllum scortechini (Hook. f.) Schltr. 3.2.1.1.25  Hippeophyllum scortechini (Hook. f.) Schltr. [From Greek hippeus = horseman, and phullon = leaf, and after Father Benedetto Scortechini (1845–1886), an Italian botanist] History: This plant was first formally described in The Flora of British India by Sir Joseph Dalton Hooker in 1888. Hooker (1817–1911) was a British botanist. Common name: Scortechini’s Hippeophyllum. Basionym: Oberonia scortechini Hook f. Habitat: It is an epiphytic orchid found in the rainforests of Malaysia and Indonesia. Diagnosis: The rhizome of Hippeophyllum scortechini (Hook. f.) Schltr. is long and creeping. The leaves are ensiform, fleshy, up to 30 cm × 1 cm, and narrowing at the apex. The scape is 50 cm long, tail-like, and covered with innumerable tiny and fleshy yellow flowers. The sepals are oblong and blunt. The petals are linear. The lip is trilobed. The side lobes are lanceolate acute. The midlobe is shorter, orbicular, and has 3 nerves (Figure 3.65). Medicinal use: In Malaysia, the leaves are heated and the juice extracted is dropped into the ears to assuage earache.

116

Medicinal Plants of China, Korea, and Japan

FIGURE 3.65  Hippeophyllum scortechini (Hook. f.) Schltr. (From Det.: R.E.H. Flora of Sumatra. Loc.: Indonesia, Sumatra, Nias, sea level. Date: August 25, 1939.)

Pharmacology: Members of the genus Hippeophyllum Schltr. are apparently void of pharmacological investigation. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory and/ or analgesic agent(s). The next plant discussed in this section is Liparis keitaoensis Hayata. 3.2.1.1.26  Liparis keitaoensis Hayata [From Greek liparos = fat, and keitaoensis = from Keitao, in Taiwan] History: This plant was first formally described in Icones Plantarum Formosanarum nec Non et Contributiones ad Floram Formosanam by Bunzo¯ Hayata in 1918. Hayata (1874–1934) was Japanese botanist. Common names: Silver cricket orchid, xin ye yang er suan (Chinese). Habitat: It is a rare terrestrial orchid found in China, Taiwan, Bhutan, India, Nepal, and Vietnam. Diagnosis: The pseudobulbs of Liparis keitaoensis Hayata are clustered, ovoid, somewhat flattened, 3 cm × 1 cm, and enclosed by white membranaceous sheaths. The leaf is solitary. The petiole is 2.5 cm long, sheath-like, and amplexicaul. The blade is green, white, ovate, 6 cm × 3.5 cm to 10 cm × 8 cm, membranaceous, cordate at the base, and acuminate at the apex. The inflorescence is 6–25 cm long. The rachis is densely flowered. The flowers are green, minute, and innumerable. The sepals are linear, 0.6 cm long, revolute, and obtuse at the apex. The petals are filiform, 0.7 cm long, and have 1 nerve. The lip is obovate, 0.6 cm in diameter, and narrowed toward the base. Medicinal use: In Taiwan, this plant is used to alleviate abdominal pains. Pharmacology: Apparently unknown. The plant may contain series of nervogenic acid glycosides that are found in Liparis condylobulbon Rchb.f.320 Bioresource: Phytochemical and pharmacological investigations and analgesic agent(s). The next plant discussed in this section is Liparis plicata Franch. & Sav.

Superorder Lilianae Takht., 1967

117

3.2.1.1.27  Liparis plicata Franch. & Sav. [From Greek liparos = fat, and from Latin plicata = pleated] History: This plant was first formally described in Enumeratio Plantarum in Japonia Sponte Crescentium by Adrien René Franchet in 1879. Franchet (1834–1900) was a French botanist. Common name: Lian chi yang er suan (Chinese). Habitat: This rare epiphytic orchid grows on trees, rocks, or cliffs in a geographical area covering China, Taiwan, Bhutan, India, Indonesia, Japan, Malaysia, Burma, the Philippines, Thailand, and Vietnam. Diagnosis: The pseudobulbs of Liparis plicata Franch. & Sav. are densely arranged, ovoid, and 0.8 cm × 0.5 cm. The leaf is solitary. The petiole is 2.5 cm long and articulate. The blade is cuneate, 10 cm × 1 cm to 22 cm × 3 cm, papery, contracted at the base into a petiole, and acuminate at the apex. The inflorescence is 25 cm long. The rachis is arching, 10 cm long, and with few small flowers. The flowers are yellowish green to brown. The dorsal sepal is ovate, 5.2 cm × 0.1 cm, and obtuse at the apex. The lateral sepals are elliptical, 0.5 cm × 0.15 cm, and obtuse at the apex. The petals are narrowly linear and 0.5 cm long. The lip is broadly oblong, 0.5 cm long, and round at the apex. The fruits are capsular, ovoid, and 1 cm × 0.5 cm (Figure 3.66). Medicinal uses: In China, the plant is used to break fever and to treat cough and sore throat. Pharmacology: Apparently unknown. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory agent(s). The next plant discussed in this section is Luisia teres Lindl. 3.2.1.1.28  Luisia teres Lindl. [After Luis de Torres, a Portuguese botanist (died 1493), and from Latin teres = cylindrical, circular in cross-section] History: This was first formally described in Folia Orchidacea by John Lindley in 1853. Lindley (1799–1865) was a British botanist.

FIGURE 3.66  Liparis plicata Franch. & Sav.

118

Medicinal Plants of China, Korea, and Japan

Common names: Stick orchid, cha chun chai zi gu (Chinese), booran (Japanese). Habitat: It is a gracile epiphytic orchid that grows on trees in the forests of China, Taiwan, Japan, and Korea. Diagnosis: The stems of Luisia teres Lindl. are pendulous, 50 cm long, fleshy, cylindrical, light green, and 0.3 cm in diameter. The internodes are 3 cm long. The leaves are linear and 7 cm × 0.2 cm to 13 cm × 0.3 cm. The inflorescence is 1 cm long and has 1–7 flowers. The flowers are fleshy and greenish purple. The lip is marked with purple. The dorsal sepal is ovate-oblong, 1 cm × 0.6 cm, and obtuse. The lateral sepals are acute and winged at the apex. The petals are falcate, 1.5 cm × 0.5 cm, and obtuse. The lip is 1.6 cm long and fleshy. The hypochile is concave. The epichile is ovate, large, and bilobed. The rostrellum is large and bilobed (Figure 3.67). Medicinal use: This plant is used in Japan and China for the treatment of gout. Pharmacology: The pharmacological property of the genus Luisia Gaudich. is apparently unknown. Bioresource: Phytochemical and pharmacological investigations. The next plant discussed in this section is Macodes petola (Blume) Lindl. 3.2.1.1.29  Macodes petola (Blume) Lindl. [From Greek macro = long, and petola = unknown meaning] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië by Karl Ludwig von Blume in 1825. Blume (1796–1862) was deputy director of agriculture in Bogor. Common names: Jewel orchid, bunga batak (Malay). Basionym: Neottia petola Blume. Habitat: It is a tiny terrestrial orchid found in damp spots in the rainforests of Malaysia and Indonesia. It is cultivated as an ornamental plant.

FIGURE 3.67  Luisia teres Lindl. (From Coll.: F. Miyushi. Det.: Hatusima.Flora of Japan. Loc.: Atsu-gase, Ohnejime-Choo, Kimotsuki-Gun, Ohsumi Province, Kagoshima Prefecture, Japan.)

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Diagnosis: The stems of Macodes petola (Blume) Lindl. are short, fleshy, and pinkish. The leaves are ovate, round, 6 cm × 3.75 cm, acute, and reticulated. The petiole is 0.75 cm long. The flowering stem is hairy, 6–18 cm long, and displays 12 flowers. The sepals are lanceolate, blunt, reddish, and hairy. The petals are linear. The lip is twisted. The midlobe is narrow, spatulate, blunt, and presents a pair of fleshy hooks at the base. Medicinal use: In Malaysia, the juice extracted from this plant is dropped into the eyes to treat eye diseases. Pharmacology: The pharmacology of the genus Macodes Lindl. remains insufficiently explored. Bioresource: Phytochemical and pharmacological investigations. The next plant discussed in this section is Malaxis monophyllos (L.) Sw. 3.2.1.1.30  Malaxis monophyllos (L.) Sw. [From Greek malakos = soft, and from Latin monophyllos = one leaf] History: This plant was first formally described in Species Plantarum of Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: White Adder’s mouth, yuan zhao lan (Chinese), i sak dan yeop ran (Korean). Basionym: Ophrys monophyllos L. Synonym: Microstylis monophyllos (Pav. ex Lindl.) Lindl. Habitat: It is a little terrestrial orchid found in the forests and grasslands of China, Taiwan, Japan, Korea, Russia, Europe, and North America. Diagnosis: The pseudobulbs of Malaxis monophyllos (L.) Sw. are ovoid, 0.9 cm × 0.5 cm, and enclosed in a white membranaceous sheath. The leaves are glossy, elliptical, 2.5 cm × 1 cm to 7.5 cm × 3 cm, amplexicaul, and acute at the apex. The inflorescence is erect, up to 40 cm long, and densely flowered. The rachis grows to 20 cm long. The flowers are yellowish, fleshy, innumerable, and minute. The dorsal sepal is lanceolate, 0.4 cm long, acuminate at the apex, and has 1 nerve. The lateral sepals are linear, 0.2 cm long, and have 1 nerve. The petals are filiform and minute. The lip is ovate, 0.4 cm long, and caudate. The fruits are capsular, ovoid, and 0.6 cm long (Figure 3.68). Medicinal use: In China, the plant is used to excite the discharge of urine.

FIGURE 3.68  Malaxis monophyllos (L.) Sw.

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Medicinal Plants of China, Korea, and Japan

Pharmacology: The pharmacological properties of members of the genus Malaxis Sol. ex Sw. are apparently insufficiently explored. Bioresource: Phytochemical and pharmacological investigations and diuretic agent(s). The next plant discussed in this section is Nervilia aragoana Comm. ex Gaudich. 3.2.1.1.31  Nervilia aragoana Comm. ex Gaudich. [From Latin nervus = nerved, and aragoana = Aragoa-like] History: This plant was first formally described in Voyage Autour du Monde Entrepris par Ordre du Roi, Exécuté sur les Corvettes l’Uranie et la Physicienne Pendant les Années 1817–1818–1819–1820” by Charles Gaudichaud-Beaupré in 1829. Gaudichaud-Beaupré (1789–1854) was a French botanist. Common names: Tall shield orchid, daun satu tahun (Malay). Habitat: It is a strange terrestrial orchid found in the grassy spots and rainforests of India, Thailand, and Malaysia. Diagnosis: The leaf of Nervilia aragoana Comm. ex Gaudich. is odd, solitary, reniform, glabrous, glossy, up to 30 cm in diameter, and often displays a row of black spots. The petiole is 20 cm long and purple. The flowering stems are 55 cm long and tail-shaped. The inflorescence carries 10 flowers that are pale green and 3 cm long. The sepals and petals are lanceolate and acute. The lip is trilobed. The side lobes are blunt. The midlobe is ovate, acute, hairy, and white with green lines (Figure 3.69). Medicinal use: In Malaysia, the leaves are boiled in water and the liquid obtained is drunk as a postpartum protective remedy. Pharmacology: An extract of Nervilia aragoana Comm. ex Gaudich. displayed antifungal activity against the fungi Saccharomyces cerevisiae, Aspergillus niger, Aspergillus fumigatus, and Cryptococcus neoformans cultured in vitro and showed antioxidant effect in the

FIGURE 3.69  Nervilia aragoana Comm. ex Gaudich. (From Coll.: Haniff. Det.: Seidenf. and Wood. Singapore Botanic Gardens. Flora of Perak. No. 13558. Date: June 15, 1924.)

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2,2-diphenyl-1-picrylhydrazyl experiment on probable account of flavonoids.321,322 Note that Nervilia fordii (Hance) Schltr. afforded a kaempferol derivative that inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides achieving an IC50 value of 16.8 μM.323 In addition, an extract of Nervilia fordii (Hance) Schltr. increased the life span of cancerous rodents.324 Bioresource: Antifungal agent(s). The next plant discussed in this section is Oberonia anceps Lindl. 3.2.1.1.32  Oberonia anceps Lindl. [After Oberon = king of fairies, and from Latin anceps = two-edged] History: This plant was first formally described in Sertum Orchidaceum by John Lindley in 1838. Lindley (1799–1865) was a British botanist. Common name: Sakat lidah buaya (Malay). Habitat: It is a little epiphytic orchid found in the rainforests of Malaysia, Burma, the Philippines, and Indonesia. It is cultivated as an ornamental plant. Diagnosis: The stems of Oberonia anceps Lindl. are 25 cm long. The leaves are cultrate, numerous, and 1.5 cm long. The spike is cylindrical, 10 cm long, curved, and densely flowered. The flowers are minute and innumerable. The sepals are ovate. The petals are linear, reflexed, and smaller than the sepals. The lip is ovate, emarginate, and ochre. The capsules are globose and sessile (Figure 3.70). Medicinal use: In Malaysia, the leaves are used to heal boils. Pharmacology: Members of the genus Oberonia Lindl. have apparently not been studied for pharmacology. One might be curious to isolate antibacterial agents from Oberonia anceps Lindl. Bioresource: Phytochemical and pharmacological investigations and antibacterial agent(s). The next plant discussed in this section is Papilionanthe hookeriana (Rchb. f.) Schltr.

FIGURE 3.70  Oberonia anceps Lindl. (From Det.: M. Ramos. Singapore Botanic Gardens. Flora of the Philippines. Date: 1923.)

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Medicinal Plants of China, Korea, and Japan

3.2.1.1.33  Papilionanthe hookeriana (Rchb. f.) Schltr. [From Greek papilio = butterfly, and anthos = flower, and after Sir William Jackson Hooker (1785–1865), an English botanist and the first director of the Royal Botanic Gardens, Kew] History: This plant was first formally described in Bonplandia by Heinrich Gustav Reichenbach in 1856. Reichenbach (1823–1889) was a German botanist. Common names: The Kinta weed, Hooker’s Papilionanthe. Synonym: Vanda hookeriana Rchb. f. Habitat: It is a terrestrial orchid found in the swamps of Malaysia and Indonesia. It is also cultivated as an ornamental plant. Diagnosis: The stems of Papilionanthe hookeriana (Rchb. f.) Schltr. are slender and 50 cm long. The leaves are coriaceous, terete, and 6–10 cm long. The inflorescence is a raceme. The flowers are massive, 10 cm long, and membranaceous. The peduncles are 18–25 cm long. The upper sepal is obovate and pale rose-colored. The lateral sepals are oblong and white. The petals are obovate, twisted, and pinkish. The lip is 4.5 cm long. The spur is very short (Figure 3.71). Medicinal use: In Malaysia, this plant is reduced into a paste that is applied externally to treat arthritis. Pharmacology: Poor pharmacological attention has been received so far by the genus Papilionanthe Schltr. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory agent(s). The next plant discussed in this section is Pholidota chinensis Lindl. 3.2.1.1.34  Pholidota chinensis Lindl. [From Greek pholis = a horny scale, and from Latin chinensis = from China] History: This plant was first formally described in Journal of the Horticultural Society of London by John Lindley in 1847. Lindley (1799–1865) was a British botanist. Common names: Chinese Pholidota, rattlesnake orchid, shi xian tao (Chinese). Habitat: This epiphytic orchid is found in the forests of China, Burma, and Vietnam. It is grown as an ornamental plant.

FIGURE 3.71  Papilionanthe hookeriana (Rchb. f.) Schltr. (From Coll.: Lake and Kelsall. Flora of Johor. The Herbarium. Botanic Gardens Singapore. Loc.: Malaysia, Kuala Natu Pahat. Date: October 10, 1892.)

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Diagnosis: The pseudobulbs of Pholidota chinensis Lindl. are 1.5 cm × 0.5 cm to 8 cm × 2 cm. The petiole is 2 cm long and supports a pair of leaves. The blade is elliptical, 5 cm × 2 cm to 20 cm × 6 cm, with 3 nerves, and acute at the apex. The leaves are 12–35 cm long. The rachis is arching and bears up to 20 flowers. The flowers are whitish, membranaceous, and minute. The dorsal sepal is elliptical, cymbiform, 1 cm × 0.6 cm, and carinate. The lateral sepals are ovate and carinate. The petals are lanceolate and 1 cm × 0.25 cm. The lip is broadly ovate, trilobed, saccate, and with a pair of orbicular lateral lobes on both sides. The midlobe is ovate, 0.4 cm × 0.5 cm, and mucronate. The fruits are capsular, ovoid, and 1.5 cm × 1 cm (Figure 3.72). Medicinal uses: In China, this plant is used to treat tuberculosis, hemorrhages, cough, asthma, rheumatism, dysentery and toothache. Constituents: Pholidota chinensis Lindl. is known to contain series of phenanthrene derivatives including phochinenins A–F, as well as biaryl compounds including phochinenins G–L, gymconpin C4, blestrianol A2, and flavanthrin.325 Pharmacology: The anti-inflammatory property of the plant has been validated: Pholidota chinensis Lindl. contains series of stilbenes, of which pholidotol A and pholidotol B inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides and interferon gamma.326 OCH3 O OH

O OH Pholidotol A

Wu and coworkers327 isolated some cytotoxic stilbenes from this plant. One might be curious to look for antimycobacterial agents in this plant.

FIGURE 3.72  Pholidota chinensis Lindl.

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Bioresource: In vitro pharmacological study of pholidotol A for its effect on neurodegeneration. The next plant discussed in this section is Pholidota yunnanensis Rolfe. 3.2.1.1.35  Pholidota yunnanensis Rolfe [From Greek pholis = a horny scale, and from Latin yunnanensis = from Yunnan] History: This plant was first formally described in Journal of the Linnean Society, Botany by Robert Allen Rolfe in 1903. Rolfe (1855–1921) was a British botanist. Common name: Yun nan shi xian tao (Chinese). Habitat: It is an epiphytic orchid found in the forests of China and Vietnam. Diagnosis: The rhizome of Pholidota yunnanensis Rolfe is creeping, 0.5 cm in diameter, branched, and densely covered by leathery sheaths. The pseudobulbs are cylindrical, 2 cm × 0.6 cm to 5 cm × 0.8 cm, attenuate toward the apex, and packed in leathery sheaths. The leaves are arranged in pairs. The blade is shortly petiolate, narrowly elliptical, 6 cm × 0.7 cm to 15 cm × 2.5 cm, papery, and round at the apex. The inflorescence is 15 cm long. The rachis has 15–20 flowers and is flexuous toward the base. The flowers are white, 0.4 cm in diameter, and arranged like scales. The dorsal sepal is broadly ovate, concave, 0.3 cm × 0.2 cm, and dorsally carinate. The lateral sepals are broadly ovate, concave, and carinate. The petals are similar to the dorsal sepal. The lip is sigmoid, obovate, 0.4 cm × 0.3 cm, and emarginate at the apex. The rostellum is broadly ligulate. The fruits are capsular, ovoid, and 1 cm × 0.5 cm, with 3 ridges (Figure 3.73). Medicinal uses: In China, the plant is cooked with meat to make a soup eaten to treat cough and asthma. Constituents: The plant is known to contain triterpenes.328,329 Pharmacology: The anti-inflammatory property of Pholidota yunnanensis Rolfe is confirmed: it produces phenanthrene derivatives of which phoyunnanins A–C, lusianthridin, eulophiol, and imbricatin showed antioxidant effects in the 2,2-diphenyl-1-picrylhydrazyl

FIGURE 3.73  Pholidota yunnanensis Rolfe.

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experiment with EC50 values of 8.8–55.9 μM.330 Besides, this plant contains the phenanthrene derivatives phoyunnanin D and E and the stilbenes phoyunbene A–D that inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides and interferon gamma.331 Bioresource: In vitro pharmacological study of eulophiol for prevention of skin ageing. The next plant discussed in this section is Platanthera japonica (Thunb. ex A. Murray) Lindl. 3.2.1.1.36  Platanthera japonica (Thunb. ex A. Murray) Lindl. [From Greek platys = flat, and anthera = anther, and from Latin Japonica = from Japan] History: This plant was first formally described in Systemat Vegetabilium. Editio Decima Quarta by Carl Peter Thunberg in 1784. Thunberg (1743–1828) was a Swedish botanist. Common names: She chun lan (Chinese), gal mae gi nan cho (Korean). Basionym: Orchis japonica Thunb. ex A. Murray. Habitat: This terrestrial orchid grows in the forests and grasslands of China, Korea, and Japan. Diagnosis: Platanthera japonica (Thunb. ex A. Murray) Lindl. is 80 cm tall. The roots are tuberous. The stems are erect, straight, stout, with several tubular sheaths at the base, and support 4–6 leaves. The leaves are cauline, alternate, widely spaced, elliptical, 10 cm × 3 cm to 20 cm × 7.5 cm, sheathing at the base, and obtuse at the apex. The rachis is 15 cm long and densely flowered. The flowers are pure white. The dorsal sepal is erect, hooded, ovate, cymbiform, 0.7 cm × 0.5 cm, glabrous, with 3 nerves, and obtuse at the apex. The lateral sepals are reflexed, ovate, oblique, 0.9 × 0.5 cm, with 3 nerves, and acute at the apex. The petals are linear, 0.7 cm long, with 1 nerve, and obtuse at the apex. The lip is conspicuously pendulous, linear, 1.5 cm long, entire, and obtuse at the apex. The spur is pendulous, cylindrical, 2.5 cm long, slender, and acute at the apex. The rostellum is erect, broadly triangular, and short (Figure 3.74).

FIGURE 3.74  Platanthera japonica (Thunb. ex A. Murray) Lindl.

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Medicinal Plants of China, Korea, and Japan

Medicinal use: In China, this plant is used to facilitate the circulation of blood. Pharmacology: To date, members of the genus Platanthera Rich. have not been studied for pharmacology. Bioresource: Phytochemical and pharmacological investigations. The next plant discussed in this section is Pleione bulbocodioides (Franch.) Rolfe. 3.2.1.1.37  Pleione bulbocodioides (Franch.) Rolfe [After Pleione, mother of the Pleiades, and from Latin bulbocodoides = Bulbocodium-like] History: This plant was first formally described in Nouvelles Archives du Muséum d’Histoire Naturelle” by Adrien René Franchet in 1888. Franchet (1834–1900) was a French botanist. Common names: Pleione orchid, du suan lan (Chinese). Basionym: Coelogyne bulbocodioides Franch. Habitat: This terrestrial orchid grows on mossy rocks in the forests of China. It is also cultivated as an ornamental plant. Diagnosis: The pseudobulb of Pleione bulbocodioides (Franch.) Rolfe is ovoid, 2.5 cm × 2 cm, and presents a single leaf. The blade is elliptical, 10 cm × 2 cm to 25 cm × 5 cm, papery, attenuate at the base, and acute at the apex. The inflorescence is erect. The flowers are solitary, large, showy, pink, and present dark purple spots on the lip. The dorsal sepal is lanceolate, 5 cm × 0.7 cm, and acute at the apex. The lateral sepals are narrowly elliptical, slightly oblique, 5 cm × 1 cm, and acute at the apex. The petals are oblanceolate, oblique, 5 cm × 0.7 cm, and acute at the apex. The lip is obovate, 4.5 cm wide, cuneate at the base, obscurely trilobed, and lacerate. The fruits are capsular, ovoid, and 3.5 cm long (Figure 3.75).

FIGURE 3.75  Pleione bulbocodioides (Franch.) Rolfe.

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Medicinal uses: In China, this plant is used to treat tuberculosis and asthma and a paste of the plant is applied to boils and snakebites. Constituents: Pleione bulbocodioides (Franch.) Rolfe is known to contain stilbenes including shanciol G and H. In addition, the plant contains lusianthridin and coelonin.332−335 Pharmacology: Note that coelonin and lusianthridin inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides with IC50 values of 9.6–19.5 μM.304 One might be curious to investigate the plant for antimycobacterial agents. Bioresource: In vitro pharmacological study of coelonin for its effect on skin ageing, and mycobactericidal agent(s). The next plant discussed in this section is Plocoglottis javanica Blume. 3.2.1.1.38  Plocoglottis javanica Blume [From Greek ploke = binding together, and glotta = tongue, and from Latin javanica = from Java] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië of Karl Ludwig von Blume in 1825. Blume (1796–1862) was deputy director of agriculture in Bogor. Common name: Java Plocoglottis. Habitat: It is a terrestrial orchid found in the rainforests of Malaysia and Indonesia. Diagnosis: The rhizome of Plocoglottis javanica Blume is creeping. The leaves are solitary, broadly elliptical, and 30 cm × 10 cm. The petiole is 15 cm long. The scape is 60 cm long. The flowers are small. The upper sepal is linear, acute, and 1.5 cm long. The lateral sepals are falcate. The petals are narrow and yellow with red spots. The lip is truncate and pale yellow (Figure 3.76). Medicinal use: In Malaysia, the fruits are roasted and the juice extracted is dropped into the ears to treat earache.

FIGURE 3.76  Plocoglottis javanica Blume. (From Malay Peninsula. Loc.: Malaysia, State of Johor. Date: 1892.)

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Medicinal Plants of China, Korea, and Japan

Pharmacology: To date, the genus Plocoglottis Blume has apparently not been studied for pharmacology. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory agent(s). The next plant discussed in this section is Spiranthes sinensis (Pers.) Ames. 3.2.1.1.39  Spiranthes sinensis (Pers.) Ames [From Greek speira = spiral, and anthos = flower referring to the coiled or spiral character of the inflorescence, and from Latin sinensis = from China] History: This plant was first formally described in Synopsis Plantarum by Christiaan Hendrik Persoon in 1807. Persoon (1761–1836) was a South African botanist. Common names: Chinese Spiranthes, shou cao (Chinese), nejibana (Japanese), ta rae nan cho (Korea). Basionym: Neottia sinensis Pers. Habitat: It is a rare terrestrial orchid found in moist areas in the forests of China, Afghanistan, Bhutan, India (specifically Kashmir), Japan, Korea, Malaysia, Mongolia, Myanmar, Nepal, the Philippines, Siberia, Thailand, Vietnam, and Australia. Diagnosis: Spiranthes sinensis (Pers.) Ames is 30 cm tall. The root is 0.5 cm in diameter. The leaves are erect, linear, and 3 cm × 0.5 cm to 10 cm × 1 cm. The inflorescence is erect, 10–25 cm long, and glabrous. The rachis is 4–10 cm long, fleshy, green, with numerous tiny spirally arranged flowers. The flowers are purplish. The dorsal sepal is cymbiform, 0.4 cm × 0.1 cm, glabrous, and subacute at the apex. The lateral sepals are lanceolate, oblique, 0.5 cm × 0.2 cm, glabrous, convex at the base, and subacute at the apex. The petals are rhombic, oblique, membranaceous, and obtuse at the apex. The lip is broadly oblong, 0.55 cm × 0.25 cm, and shortly clawed. The rostellum is narrowly triangular. The stigma is discoid, trilobed, and slightly raised (Figure 3.77).

FIGURE 3.77  Spiranthes sinensis (Pers.) Ames. (From Coll.: S.N. Phoon and J.J. Vermeulen. Flora of Malaya. Forest Research Institute Malaysia (KEP) Kepong, Malaysia. No. 53230. Loc.: Malaysia, Pahang, Cameron Highlands, Ipoh-Brinchang New Road, New road from Brinchang to Simpang Pulai. Wayside. Lower montane forest. Roadside, rich soil, 4°34.59′–101°23.46′ E. Alt.: 1382 m. Date: February 3, 2007.)

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Medicinal uses: In China, this plant is cooked with meat to make a soup eaten to cure fatigue, to check hemoptysis, and to treat kidney diseases. Constituents: Spiranthes sinensis (Pers.) Ames stores the phenanthrene derivatives sinensols A–H, as well as the homocyclotirucallane sinetirucallol and prenylated coumarins.336−338 Pharmacology: One might be curious to look for antimycobacterial agents here as weakness and hemoptysis are classical symptoms of tuberculosis. Bioresource: Antimycobacterial agent(s). The next plant discussed in this section is Thrixspermum pardale (Ridl.) Schltr. 3.2.1.1.40  Thrixspermum pardale (Ridl.) Schltr. [From Greek thrix = hair, and sperma = seed, and from Latin pardalis = a leopard] History: This plant was first formally described in Transactions of the Linnean Society of London, Botany by Sir Henry Nicholas Ridley in 1893. Ridley (1855–1956) was a British botanist. Basionym: Sarcochilus pardalis Ridl. Habitat: This rare little epiphytic orchid grows on trees and shrubs in the rainforests of Malaysia and Indonesia. Diagnosis: The stems of Thrixspermum pardale (Ridl.) Schltr. are 30 cm long. The leaves are spatulate, acute, and 6 cm × 3 cm. The scape is 30 cm long and slender. The raceme is 6 cm long and thickened with crowded bracts. The flowers are 1.5 cm wide. The sepals are ovate and blunt. The petals are linear white with pink spots. The lip is cuneate, truncate, yellowish red, and covered with white wool. The capsules are narrow, linear, and 10 cm long (Figure 3.78). Medicinal use: In Malaysia, this plant is used to heal ulcers.

FIGURE 3.78  Thrixspermum pardale (Ridl.) Schltr. (From Coll. and Det.: J.J. Vermeulen. Singapore Botanic Gardens. 1891. Date: July 30, 2004.)

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Medicinal Plants of China, Korea, and Japan

Pharmacology: The pharmacological properties of members of the genus Thrixspermum Lour. are apparently insufficiently explored. Phenanthrenes or stilbenes are probably involved in the medicinal property of the plant. Bioresource: Antibacterial agent(s). The next plant discussed in this section is Tropidia curculigoides Lindl. 3.2.1.1.41  Tropidia curculigoides Lindl. [From Greek tropideion = keel, and Latin curculigoides = curculigo-like] History: This plant was first formally described in The Genera and Species of Orchidaceous Plants of John Lindley in 1840. Lindley (1799–1865) was a British botanist. Habitat: It is a terrestrial orchid found in the rainforests of India, Sri Lanka, Thailand, Malaysia, and Indonesia. Diagnosis: The leaves of Tropidia curculigoides Lindl. are elliptical, plicate, membranaceous, 18 cm × 3 cm to 25 cm × 4.5 cm, dark green, and glossy. The raceme is axillary, 1.5 cm long, and bears many broad ovate ribbed bracts. The flowers are 0.75 cm long, greenish white, and vanilla-scented. The sepals are lanceolate. The petals are linear falcate. The lip is lanceolate (Figure 3.79). Medicinal uses: In Malaysia, the roots are boiled in water and the liquid obtained is drunk to treat diarrhea. This plant is also used to break malarial fever. Pharmacology: The genus Tropidia Lindl. has apparently not been studied for pharmacology. Bioresource: Phytochemical and pharmacological studies and antimalarial agent(s). The next plant discussed in this section is Vanilla griffithii Rchb. f. 3.2.1.1.42  Vanilla griffithii Rchb. f. [From Spanish vainilla = a pod, and after Dr. William Griffith (1810–1845), British surgeon and botanist in Malaysia] History: This plant was first formally described in Bonplandia by Heinrich Gustav Reichenbach in 1854. Reichenbach (1823–1889) was a German botanist. Common names: Akar punubal, telinah kerbau bukit (Malay).

FIGURE 3.79  Tropidia curculigoides Lindl. (From Flora of Singapore. Date: February 1, 1996.)

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FIGURE 3.80  Vanilla griffithii Rchb. f.

Habitat: This orchid is a climber that grows on trees and waterfall rocks in the rainforests of Malaysia. Diagnosis: The stems of Vanilla griffithii Rchb. f. are dull light green, terete, 5 m long, and rooting at the nodes. The leaves are fleshy, dull light green, lanceolate, and 18 cm × 9 cm. The raceme is axillary, 6 cm long, and stout. The flowers are numerous, 6 cm wide, showy, and white. The sepals are ovate. The petals are linear-obovate. The side lobes of the lip are round. The midlobe is bilobed. The fruits are capsular, sweet, edible, 7.5 cm × 1.5 cm, dark green, fusiform, and fleshy (Figure 3.80). Medicinal uses: In Malaysia, the fresh flowers are pounded with water and the paste obtained is rubbed on the body to break fever. The leaves and stems are used to strengthen the hair. Pharmacology: Apparently insufficiently explored. The antipyretic property of the plant may be owed to vanillin that impaired the activation of nuclear factor-kappa B and the gene expression of cyclooxygenase-2 in murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.339 Bioresource: In vitro pharmacological study of vanillin for its effect on neurodegeneration. Antipyretic and anti-inflammatory agents abound in the next clade: the order Liliales.

3.2.2  Order Liliales Perleb, 1826 The order Liliales consists of 10 families of flowering plants of which the family Liliaceae is ­discussed here. 3.2.2.1  Family Liliaceae Juss., 1789, nom. cons., the Lily Family The family Liliaceae sensu lato is a vast clade that consists of about 250 genera and 4000 species of lilies that are ubiquitous. Liliaceae are perennial and grow from a bulb or a rhizome or a corm. Chemically, members of this large family are notorious for accumulating large amounts of steroidal saponins, some steroid alkaloids, and alkaloids derived from phenylalanine or tyrosine. The leaves are simple, alternate, and often fleshy with narrow parallel secondary nerves. The inflorescence is a raceme or a spike. The perianth comprises 6 tepals. The androecium includes 6 stamens. The anthers are conspicuous, tetrasporangiate, and dithecal. The gynoecium consists of 3 carpels that are united

132

Medicinal Plants of China, Korea, and Japan

to form a compound, superior ovary with axile placentation. The style is protruding and develops 3 stigmas. The fruits are soft, capsular, loculicidal, or scepticidal. CH3 CH3 CH3

O

H

CH3

O

H H H

H

HO Diosgenin

H3C O

H3CO

H OH

NH HO

H

H3CO

H OCH3 O

H O

OCH3 Colchicine

 

H

O N

Lycorine



OH HO

OH

OH

O O H O

OH

H3CO

N OH

 

NH

H

CH3

O

Pancratistatin



Galanthamine

To this large family belong several ornamental plants such as Agave americana L. (century plant), Amaryllis belladonna L. (belladona lily), Aspidistra lurida Ker Gawl. (variegated cast-iron plant), Chionodoxa luciliae Boiss (glory of the snow)., Crinum asiaticum L. (crinum lily), Lilium longiflorum Thunb. (Easter lily), Muscari racemosum (L.) Mill. (grape hyacinth), Narcissus jonquilla L. (true jonquil), Ornithogalum arabicum L. (star of Bethlehem), Scilla bifolia L. (Alpine squill), Trillium ovatum Pursh (Pacific trillium), and Tulipa clusiana DC (lady tulip). Asparagus officinalis L. (garden asparagus), Allium cepa L. (onion), Allium sativum L. (garlic), and Allium porrum L. (leek) are cultivated for food. Some lilies are particularly poisonous such as Zigadenus venenosus S. Watson (death camas) and Veratrum album L. (white Hellebore). Members of the

Superorder Lilianae Takht., 1967

133

genus Dioscorea L. accumulate in their tubers spirostane saponins (sapogenins) such as dioscin that produces diosgenin after fermentation and hydrolysis. Diosgenin is used for the synthesis of progesterone, hydrocortisone, and other steroids of therapeutic value. Examples of such plants are Dioscorea composita Hemsl., Dioscorea floribunda Mart. & Gall., Dioscorea spiculiflora Hemsl., and Dioscorea mexicana Guill. in Mexico, Dioscorea zingiberensis C.H. Wright and Dioscorea panthaica Prain & Burk. in China, and Dioscorea prazeri Prain & Burk and Dioscorea deltoidea Wall. in India and Pakistan. Agave sisalana Perr. and Agave fourcroides Lem. produce hecogenin, a steroid used like diosgenin for the synthesis of steroidal drugs. The dried roots of various species belonging to the genus Smilax L. (Sarsaparilla, British Pharmaceutical Codex, 1949) have been used in the form of a decoction as a vehicle and flavoring agent for medicaments and have been used to treat leprosy in Morocco. Colchicine (British Pharmacopoeia, 1963) is an alkaloid obtained from the corms and seeds of an elegant European poisonous herb: Colchicum autumnale L. It is used for the relief of pain in acute gout at a dose of 0.5–1 mg in tablet form. Colchicine is analgesic, anti-inflammatory, and antimitotic by inhibition of tubulin polymerization. The dried inflorescence of Convallaria majalis L. (Convallaria, British Pharmaceutical Codex, 1949) or lily of the valley has been used as cardiotonic on account of cardiotonic glycosides such as convallatoxin that is a rhamnoside of strophantidine. The dried sliced bulb of the white or Mediterranean squill Urginea maritima (L.) Baker or Urginea scilla Steinh. (Squill, British Pharmaceutical Codex, 1963) contains series of bufadienolides such as scillarene A that are cardiotonic. Urginea (Indian Pharmacopoeia, 1949) consists of the dried sliced bulb of the Indian squill Urginea indica (Roxb.) Kunth that has similar properties to and is used for the same purpose as the Mediterranean squill. White Veratrum (British Pharmaceutical Codex, 1934) consists of the dried rhizomes of Veratrum album L. that contains series of toxic alkaloidal saponins, of which protoveratrine A induces hypotension and bradycardia. Garlic (British Pharmaceutical Codex, 1949) or the fresh bulb of Allium sativum L. has been used as an expectorant and an antiseptic, to produce perspiration and urination, and to treat bronchitis. The Amaryllidaceae alkaloids represent a group of isoquinoline alkaloids in the Liliaceae that have attracted a considerable amount of interest due to some compelling pharmacological properties they were shown to possess. For instance, pancratistatin isolated from Hymenocallis littoralis (Jacq.) Salisb. induced apoptosis in several cancer cells.340 Galanthamine obtained from Galanthus nivalis L. is a reversible competitive inhibitor of acetylcholinesterase activity that can improve and stabilize cognitive performance and, today, is a standard first-line medication for Alzheimer’s disease.259 Galanthamine is also obtained from the Russian Caucasian snowdrop or Galanthus woronowii Losinsk. This cholinergic alkaloid has the same pharmacological property as physostigmine and has been used for its effect on myopathy and motor and sensory impairment. Another example of Amaryllidaceae alkaloid is lycorine isolated from Lycoris radiata (L’Hér.) Herb. that inhibited the replication of the severe acute respiratory syndrome-associated coronavirus cultured in vitro with an EC50 value of about 15.7 nM.251 Besides, lycorine prolonged the survival of rodentbearing brain grafts of murine melanoma (B16F10).341 The first plant to be examined in this section is Anemarrhena asphodeloides Bunge. 3.2.2.1.1  Anemarrhena asphodeloides Bunge [From Greek a = without, nema = a filament, and arrhen = male, and from Latin aspheloides = ​ asphodel-like] History: This plant was first formally described in Enumeratio Plantarum, quas in China Boreali Collegit Dr. Al. Bunge by Alexander Georg von Bunge in 1833. Bunge (1803–1890) was a Russian botanist. Common names: Common Anemarrhena, zhi mu (Chinese), chimo (Japanese), ji mo (Korean).

134

Medicinal Plants of China, Korea, and Japan

Habitat: This perennial herb is cultivated or grows wild on the mountain slopes of Manchuria, inner Mongolia, and North China. Diagnosis: Anemarrhena asphodeloides Bunge is 1 m tall. The rhizome is horizontal and thick. The leaves are grass-like and 60 cm × 2 cm. The inflorescence is 90 cm long. The flowers are arranged in an elongated raceme. The perianth is dull rose-purple and fragrant. The perianth comprises 6 tepals that are linear and 0.5 cm long. The androecium encloses 3 stamens, the anthers of which are versatile. The fruits are loculicidal capsules that are hexagonal and 1.2 cm long (Figure 3.81). Medicinal uses: In China, the rhizomes are used as a sedative, to excite the discharge of urine, to break fever, and to treat influenza, tubercular cough, pneumonia, and morning sickness. Pharmacology: Anemarrhena asphodeloides Bunge has been the subject of several pharmacological studies that have resulted in the isolation of numerous saponins, lignans, xanthones, and phenolics that exhibited an impressive array of pharmacological activities. Saponins: Sarsasapogenin isolated from the rhizomes induced apoptosis in human hepatocellular liver carcinoma (HepG2) cells through arrest of cell cycle in G2/M phase.342 In addition, sarsapogenin has an antidepressant effect in rodents.343 Timosaponin AIII obtained from this plant improved the memory of scopolamine-treated rodents in the Morris water maze experiment via inhibition of acetylcholinesterase activity.344 Besides, timosaponin AIII protected rodents against passive cutaneous anaphylaxis induced by immunoglobulin E.345 Note that timosaponin AIII is cytotoxic against tumor cells cultured in vitro.346 Anemarsaponin B, another steroidal saponin, isolated from the rhizomes of Anemarrhena asphodeloides Bunge inhibited the generation of tumor necrosis factor-alpha and interleukin-6 by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.347 Anemarrhenasaponin I, anemarrhenasaponin Ia, timosaponin BI, timosaponin BII, timosaponin BIII, anemarsaponin B, and timosaponin AIII isolated from the rhizomes abrogated the aggregation of platelets.348,349 Pseudoprototimosaponin AIII obtained from this plant lowered the glycemia of alloxan-induced diabetic rodents.350

FIGURE 3.81  Anemarrhena asphodeloides Bunge.

135

Superorder Lilianae Takht., 1967 CH3

H3C

O

CH3 O

CH3

AcO

H Sarsasapogenin

CH3 CH3 CH3

OH HO HO O

HO

O

H H

O OH

O

H

O

H O

H

H

OH

HO

Timosaponin AIII

H2C

HO HO

  

CH2

OH Nyasol



OH

Cis-hinokiresinol

Lignans: Nyasol significantly inhibited the generation of prostaglandin E2 and nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.351 Besides, nyasol isolated from this plant was antiviral against the respiratory syncytial virus A2 strain in human hepatoma (Hep-2) cells in vitro.352,353 Another lignan of interest in Anemarrhena asphodeloides Bunge is cis-hinokiresinol that showed a broad spectrum of antifungal and antibacterial activities.354 Cis-hinokiresinol inhibited the enzymatic activity of hyaluronidase, phosphodiesterase, and testosterone 5-alpha-reductase in vitro.262,355,356 Xanthones: Anemarrhena asphodeloides Bunge contains the xanthone mangiferin that attenuated nephropathy in streptozotocin-induced diabetic rodents.357 Mangiferin reduced glycemia in type 2 diabetic rodents.358 In addition, mangiferin isolated from this plant inhibited the enzymatic activity of acetylcholinesterase achieving an IC50 value of 62.8 μM. It also improved the memory of rodents poisoned with scopolamine in the Morris water maze experiment.359

136

Medicinal Plants of China, Korea, and Japan

Phenolics: The flavonoid broussonin B isolated from this plant displayed neurotrophic activity in rat pheochromocytoma (PC12) cells cultured in vitro.360 Anemarchalconyn isolated from this plant elicited a remarkable inhibitory effect against the differentiation of mouse embryonic fibroblast (3T3-L1) cells achieving an IC50 value of 5.3 μM.361 Bioresource: In vitro pharmacological study of nyasol for its effect on respiratory syncytial virus infection. The next plant discussed in this section is Asparagus cochinchinensis (Lour.) Merr. 3.2.2.1.2  Asparagus cochinchinensis (Lour.) Merr. [From Greek asparagos = Asparagus officinalis L., and from Latin cochinchinensis = from Cochinchina] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Chinese Asparagus, tian men dong (Chinese), kusa sugi kazura (Japanese), cheon moon dong (Korea). Basionym: Melanthium cochinchinense Lour. Synonyms: Asparagopsis sinica Miq., Asparagus cochinchinensis var. longifolius F.T. Wang & T. Tang, Asparagus dauricus var. elongatus Pamp., Asparagus. gaudichaudianus Kunth, Asparagus insularis Hance, Asparagus lucidus Lindl., Asparagus sinicus (Miq.) C.H. Wright. Habitat: This perennial herb grows wild in waste fields and on seashores of China, Japan, Korea, Laos, and Vietnam. It is also cultivated for food and medicine. Diagnosis: The rhizome of Asparagus cochinchinensis (Lour.) Merr. is swollen, tuberous, 1 cm × 3 cm, and edible. The stems are erect, 1.5 m tall, woody, and angled. The cladodes are falcate, 0.5 cm × 0.1 cm to 8 cm × 0.2 cm, arranged in fascicles of 3, and trigonal. The leaf spur is spinescent. The spine is 0.3 cm long. The inflorescence is axillary. The flowers of both sexes are paired and subequal. The perianth of male flowers is greenish, campanulate, and 0.3 cm long. The berries are green and 0.7 cm in diameter (Figure 3.82).

FIGURE 3.82  Asparagus cochinchinensis (Lour.) Merr.

Superorder Lilianae Takht., 1967

137

Medicinal uses: In Korea, Japan, China, Taiwan, Cambodia, Laos, and Vietnam, the rhizomes are used to cure fatigue, cough, costiveness, and inflammation and to excite the discharge of urine. In Cambodia, Laos, and Vietnam, the juice extracted from the aerial part is used to treat gastrointestinal infection. In Hong Kong, this plant is used to treat tuberculosis, breast cancer, and bronchitis. Constituents: The rhizomes of Asparagus cochinchinensis (Lour.) Merr. accumulate a substantial amount of starch and furostane steroids.362 Pharmacology: The anti-inflammatory property of this plant is confirmed: an extract inhibited 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in rodents (Lee DY et 2009).363 Asparacoside, 3′-hydroxy-4′-methoxy-4′-dehydroxynyasol, and 3″-methoxynyasol isolated from the plant abrogated the survival of human nasopharyngeal carcinoma (KB), human colon carcinoma (Col-2), human prostate adenocarcinoma (LNCaP), human lung adenocarcinoma (Lu-1), and human umbilical vein endothelial (HUVEC) cells cultured in vitro with IC50 values of 4–12 μg/mL.364 This plant contains nyasol that is toxic for brine shrimp and anti-inflammatory.351,365 Bioresource: In vitro pharmacological study of 3″-methoxynyasol for its effect on digestive cancers. The next plant discussed in this section is Cordyline terminalis (L.) Kunth. 3.2.2.1.3  Cordyline terminalis (L.) Kunth [From Greek cordyle = a club, and from Latin terminalis = end] History: This plant was first formally described in Systema Naturae by Carl Linnaeus in 1767. Linnaeus (1707–1778) was a Swedish botanist. Common names: Good luck tree, Hawaiian ti, cabbage tree, common dracaena, jeluang, litik, idahan (Malay), zhu jiao (Chinese), sen’nenboku (Japanese). Basionym: Dracaena terminalis L. Synonyms: Asparagus terminalis L., Convallaria fruticosa L., Taetsia fruticosa (L.) Merr. Habitat: It is a beautiful perennial plant found in a geographical area ranging from India to China to the Pacific islands from where it perhaps originates. It is a common ornamental plant in tropical Asia. Diagnosis: Cordyline terminalis (L.) Kunth is 3 m tall. The petiole is channeled above, dilated at the base, clasping the stems, and 30 cm long. The blade is crimson, elliptical, 25 cm × 5 cm to 50 cm × 10 cm, and cuspidate at the apex. The inflorescence is a 60-cm– long panicle with spreading branches that are 10 cm long and densely flowered. The flowers are small. The pedicel is 0.4 cm long. The perianth is reddish and presents a tube that is 0.6 cm long. The perianth lobes are erect. The stamens are inserted in the throat of the corolla and exerted. The fruits are reddish and contain several seeds. Medicinal uses: In Malaysia, this plant is used for black magic and to treat dysentery and skin diseases. In Burma, this plant is used to treat dysentery. In Indonesia, the leaves are applied to wounds inflicted by the sting of fish. In North Bougainville, this plant is used to break fever and to assuage headache. The Maoris use the leaves as a vegetable. Constituents: Note that spirostane saponins were found in Cordyline cannifolia R.Br. and furostane saponins were found in Cordyline stricta Hook. f.366,367 Pharmacology: So far, not much is known about the pharmacological potential of Cordyline terminalis (L.) Kunth. Thymidine isolated from Cordyline terminalis (L.) Kunth exhibited some cytotoxic properties against mouse lymphoma (EL4) and human breast adenocarcinoma (MCF-7) cells cultured in vitro.368 One might be curious to study further the pharmacological property of this plant.

138

Medicinal Plants of China, Korea, and Japan H3C O O

OH

N HN

OH O Thymidine

Bioresource: Phytochemical and pharmacological investigations. The next plant discussed in this section is Curculigo orchioides Gaertn. 3.2.2.1.4  Curculigo orchioides Gaertn. [From Latin curculio = a corn worm, and orchioides = orchid-like] History: This plant was first formally described in De Fructibus et Seminibus Plantarum by Joseph Gaertner in 1788. Gaertner (1732–1791) was a German botanist. Common names: Black musale, xian mao (Chinese). Synonym: Curculigo orchioides var. minor Benth. Habitat: This perennial herb grows on grassy slopes and in the forests of China, Taiwan, Cambodia, India, Indonesia, Japan, Laos, Burma, Pakistan, Papua New Guinea, Australia, the Philippines, and Vietnam. Diagnosis: Curculigo orchioides Gaertn. grows from a cylindrical rhizome that is 10 cm long. The blade is elliptical and 10 cm × 0.5 cm to 2.5 cm × 45 cm. The base is tapering and the apex is acute. The inflorescence is an umbel-like raceme with 4–6 flowers. The perianth is showy, starry, and bright yellow. The tepals are oblong. The stamens are half as long as the tepals. The fruits are bullet-shaped berries that are 1.5 cm × 0.6 cm with a 0.25-cm-long beak (Figure 3.83).

FIGURE 3.83  Curculigo orchioides Gaertn. (From Coll.: T. Tanaka and Y. Shimada. Leg.: K. Odashima. Flora of Taiwan. No. 17813. Loc.: Japan, Sirin, Taihoku-syu. Date: June 6, 1934.)

139

Superorder Lilianae Takht., 1967

Medicinal uses: In China, this plant is used to cure fatigue and impotence, to excite the discharge of urine, to treat arthritis and urogenital infection, and to break fever. In the Philippines, this plant is used to treat lung diseases, skin diseases, impotence, and headache and to excite the discharge of urine. In India, the plant is used to treat asthma and inflammation of the skin. Constituents: Curculigo orchioides Gaertn. is known to contain series of cycloartane saponins and phenyl glycosides that most probably account for the medicinal uses listed above.369,370 Pharmacology: The anti-inflammatory property of the plant has been confirmed experimentally: an extract of rhizomes exhibited antihistaminic property in vivo.371 Besides, an extract of the plant protected guinea pigs against histamine-induced bronchoconstriction and rodents against egg albumin-induced passive paw anaphylaxis.372 In addition, extracts of the plant elicited immunostimulating properties on probable account of glycosides.373,374 Wu and coworkers375 isolated curculigoside, curculigoside B, curculigoside C, and syringic acid that showed antioxidant effects. OCH3

O OH

O

OCH3 OH

O O

HO

HO

OH Curculigoside

The aphrodisiac property of this plant is confirmed: administration of 200 mg/kg body weight of an extract to rodents resulted in enhancement of penile erection.376,377 Moreover, the plant has estrogenic properties: an extract increased uterine weight, uterine glycogen content, and a proliferative change in uterine endometrium in ovariectomized rodents.378 Finally, an extract of the plant protected rodents against CCl4-induced hepatocellular damage.379 Bioresource: In vitro pharmacological study of curculigoside for its effect on skin ageing. The next plant discussed in this section is Dianella ensifolia (L.) DC. 3.2.2.1.5  Dianella ensifolia (L.) DC. [From Latin Diana = Roman sylvan goddess, ella = small stature, and ensifolia = sword-shaped leaves] History: This plant was first formally described in Mantissa Plantarum by Carl Linnaeus in 1767. Linnaeus (1707–1778) was a Swedish botanist. Common names: Cerulean flax-lily, umbrella dracaena, siak jantan (Malay), shan jian (Chinese), kikyo ran (Japanese). Basionym: Dracaena ensifolia L. Synonyms: Anthericum adenanthera Forster, Dianella ensata (Thunb. & Dallm.) R. Henderson, Dianella javanica Kunth, Dianella mauritiana Blume, Dianella montana Blume, Dianella nemorosa Lam., Dianella odorata Blume, Dianella sandwicensis Hook. & Arn., Dracaena ensata Thunb. & Dallm., Dracaena ensifolia L., Phalangium adenanthera Poir., Rhuacophila javanica Blume, Walleria paniculata Fritsch.

140

Medicinal Plants of China, Korea, and Japan

Habitat: This perennial herb is found in a geographical area covering India, China, and the Pacific islands. It grows wild in grasslands near the seaside, and is a common tropical garden ornamental plant. Diagnosis: The stems of Dianella ensifolia (L.) DC. are tufted and 60 cm tall. The leaves are narrow, grass-like, in 2 rows, and 50 cm × 1.5 cm to 80 cm × 3 cm. The blade is glossy, yellow at the margins, and obtuse at the apex. The inflorescence is a 15-cm-long panicle. The flowers display 6 tepals that are bluish, spreading, and 0.6 cm long. The anthers are fusiform and showy. The fruits are purplish berries that are 0.5 cm in diameter and glossy (Figure 3.84). Medicinal uses: In China, a paste of this plant is applied to swellings. In Cambodia, Laos, and Vietnam, this plant is used to treat fatigue. In Indonesia, this plant is used to treat gastrointestinal infection, herpes, urogenital infection, and skin infection and to excite the discharge of urine. The roots are used to make perfume. Pharmacology: The antiviral property of the plant is not validated yet, but dianellidin isolated from Dianella callicarpa G.W. Carr & P.F. Horsfall exhibited an antiviral property.380 In addition, chrysophanic acid isolated from Dianella longifolia R.Br. inhibited the replication of poliovirus types 2 and 3 cultured in vitro.381 OH

O

OH

CH3 O Chrysophanic acid

Note that the plant contains an aromatic substance, 1-(2,4-dihydrophenyl)-3-(2,4-dimethoxy-3methylphenyl) propane, that exhibited an antioxidant property in the 1-1-diphenyl-2-picryl-hydrazyl experiment with an EC50 value of 78 μM, inhibited ultraviolet-induced lipid oxidation with an EC50

FIGURE 3.84  Dianella ensifolia (L.) DC. (From Flora of Malaya. Loc.: Malaysia, Selangor, Gombak, Forest Research Institute, main road first gate.)

Superorder Lilianae Takht., 1967

141

value of 30 μM, inhibited the enzymatic activity of tyrosinase, and impaired melanin synthesis in mouse melanoma (B16-F1) cells cultured in vitro.382,383 Quinones of pharmacological interest might await discovery. Bioresource: In vitro pharmacological study of 1-(2,4-dihydrophenyl)-3-(2,4-dimethoxy-3methylphenyl) propane for its effect on skin ageing and/or darkening. The next plant discussed in this section is Dracaena angustifolia Roxb. 3.2.2.1.6  Dracaena angustifolia Roxb. [From Greek drakaina = female dragon, and from Latin angustifolia = having narrow foliage] History: This plant was first formally described in Flora Indica; or Descriptions of Indian Plants by William Roxburgh in 1832. Roxburgh (1751–1815) was a Scottish botanist. Common names: Nam ginseng, soap tree, suji (Malay), chang hua long xue shu (Chinese). Synonyms: Dracaena ensifolia Wall., Dracaena menglaensis G.Z. Ye, Pleomele angustifolia (Roxb.) N.E.Br., Sansevieria fruticosa Blume. Habitat: This perennial herbaceous plant is found in the forests and thickets in a geographical area covering India, South China, Pacific islands, Bhutan, Cambodia, Indonesia, Laos, Malaysia, Burma, Papua New Guinea, the Philippines, Thailand, Vietnam, and North Australia. It is widely cultivated as a garden and indoor ornamental plant. Diagnosis: Dracaena angustifolia Roxb. is shrubby, rhizomatous, and 3 m tall. The stems are grayish and smooth. The blade is sessile, fleshy, lanceolate, and 20 cm × 1.5 cm to 45 cm × 5 cm. The inflorescence is terminal, branched, and 50 cm long. The flowers are arranged in clusters of 2 or 3. The perianth is greenish white, 2 cm × 0.7 cm, and produces 6 lobes. The lobes of the perianth are 1 cm long. The filaments are filiform and the anthers are 0.3 cm long. The berries are orange, globose, 1.2 cm in diameter, and contain 1–2 seeds (Figure 3.85)

FIGURE 3.85  Dracaena angustifolia Roxb. (From Coll.: D. Stancik and I. Brus. Flora of Papua New Guinea. Prov.: Madang. No. 4878. Loc.: Papua New Guinea, Ohu. Primary and secondary forest, 145°41′E–05°14′S. Alt.: 200 m. Date: August 13, 2003.)

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Medicinal Plants of China, Korea, and Japan

Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used to treat lack of milk. In Indonesia, a decoction of the leaves is used to treat gonorrhea and the juice extracted from the leaves is said to render the hair long and pliant. In the Philippines, the roots are used as an antidote for insect bites and a decoction of roots is drunk to alleviate stomachache. Constituents: Dracaena angustifolia Roxb. contains series of spirostane and furostane saponins.384 Pharmacology: The spirostane saponins namonins A and B abrogated the survival of human fibrosarcoma (HT1080) cells cultured in vitro.385 Besides, the plant contains ergosterol peroxide, linoleic acid, and E-phytol that exhibited antituberculosis activity with minimum inhibiting concentrations less than or equal to 2 μg/mL.386 The analgesic property of the plant has not been validated yet, but one can reasonably infer that saponins are involved as steroidal saponins extracted from Dracaena ombet Kotschy & Peyr. ­displayed both anti-inflammatory and analgesic properties.387 O

CH3

OH

OCH3 HO R1

R2

Retrodihydrochalcone



CH3

HO Estradiol

CH3

CH3

CH3

H3C

OH E-phytol

Note that some retrodihydrochalcones isolated from Dracaena loureioi (Lour.) Gagnep. showed some affinity for estrogen receptors in vitro.388 Bioresource: In vitro pharmacological study of retrodihydrochalcone for its effect on the postmenopausal syndrome. The next plant discussed in this section is Erythronium japonicum Decne. 3.2.2.1.7  Erythronium japonicum Decne. [From Greek eruthe¯ma = red, and from Latin japonicum = from Japan] History: This plant was first formally described in Revue Horticole by Joseph Decaisne in 1854. Decaisne (1807–1882) was a French botanist. Common names: Fawn Lily, trout lily, zhu ya hua (Chinese), katakuri (Japanese), eol re ji (Korean). Synonyms: Erythronium dens-canis var. japonicum Baker, Erythronium. japonicum var. album C.F. Fang, Erythronium japonicum var. immaculatum P.Y. Fu & Q.S. Sun. Habitat: This perennial herb grows in moist places of the forests of China, Japan, and Korea. It is cultivated for food and as an ornamental plant. Diagnosis: Erythronium japonicum Decne. is 20 cm tall and develops from a pure white, starchy, and edible bulb. The bulb is 6 cm × 1 cm. The petiole is 4 cm long. The blade is broadly elliptical, 10 cm × 2 cm to 11 cm × 6 cm, glabrous, cuneate at the base, and mucronate at the apex. The flowers are solitary and showy. The perianth comprises 6 tepals

Superorder Lilianae Takht., 1967

143

FIGURE 3.86  Erythronium japonicum Decne. (From Coll.: F. Miyoshi. Plants of Japan. No. 43893. Loc.: Japan, Honna Kana-yama-choo, Ohnuma-gun, Fukushima prefecture, Hondo, Iwashido province. Date: May 5, 1966.)

that are purple, lanceolate, and 3.5 cm × 0.7 cm to 5 cm × 1 cm. The filaments are filiform and unequal in length. The anthers are oblong and 0.5 cm long. The style is longer than the stamens. The stigma is short and trilobed (Figure 3.86). Medicinal uses: In Korea, the bulb is used to cure fatigue and to treat diarrhea. In Japan, the bulb is used to cure fatigue and as a laxative. Constituents: Isono389 has studied the constituents of the plant. Butyrolactones have been found in Erythronium grandiflorum Pursh.390 Pharmacology: One might be curious to study the nootropic properties of the plant. Bioresource: Phytochemical and pharmacological investigations and nootropic agent(s). The next plant discussed in this section is Eurycles amboinensis (L.) Loudon. 3.2.2.1.8  Eurycles amboinensis (L.) Loudon [After Caius Lulius Eurycles, a benefactor of Greek cities, and from Latin amboinensis = from Ambon] History: This plant was first formally described in Species Plantarum of Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Cardwell lily, daun sapenoh, bunga sepenuh (Indonesia). Synonym: Pancratium amboinense L. Habitat: It is a perennial herb that grows wild along the seashores and in rocky spots of Malaysia, the Philippines, Indonesia, and Australia. It is grown as a garden and indoor ornamental plant. Diagnosis: The leaves of Eurycles amboinensis (L.) Loudon are ovate, fleshy, glossy, and 40 cm long. The blade has 30 pairs of secondary nerves. The petiole is 15–35 cm long. The inflorescence is an umbel of 20 flowers. The perianth is showy, 3 cm long, and displays 6 lobes that are oblong and pure white.

144

Medicinal Plants of China, Korea, and Japan

Medicinal uses: In the Philippines, small doses of raw bulbs are ingested to induce vomiting and the leaves are applied to treat rheumatism. In Malaysia, this plant is used for magic and is believed to prevent spirits from haunting houses. Constituents: The leaves contain methyl eugenol, aliphatic hydrocarbons, and long-chain carboxylic acids.391 Pharmacology: Eurycles amboinensis (L.) Loudon contains traces of the alkaloid lycorine that inhibited the generation of tumor necrosis factor-alpha by macrophages stimulated with bacterial lipopolysaccharides.392 OCH3

H OH HO H

H3CO

H

O H O

CH2



Methyl eugenol



N

Lycorine

Bioresource: Phytochemical and pharmacological investigations and anticancer alkaloid(s). The next plant discussed in this section is Fritillaria thunbergii Miq. 3.2.2.1.9  Fritillaria thunbergii Miq. [From Latin fritillus = a chess board, and after Carl Peter Thunberg (1743–1828), a Swedish botanist and physician who traveled with the ships of the Dutch East India Company] History: This plant was first formally described in Annales Museum Botanicum LugdunoBatavi by Friedrich Anton Wilhelm Miquel in 1867. Miquel (1811–1871) was a Dutch botanist. Common names: Chinese Fritillaria, zhe bei mu (Chinese), setsubaimo (Japanese), jung guk pae mo (Korean). Habitat: This superb perennial herb is found in the forests of China and Japan. It is cultivated as a garden ornamental plant. Diagnosis: The bulb of Fritillaria thunbergii Miq. is edible and consists of 2–3 scales that are dirty white, garlic-like, ovoid, and 3 cm in diameter. The stems are 80 cm tall. The leaves are membranaceous and opposite or alternate. The blade is linear-lanceolate, 7 cm × 1 cm to 10 cm × 2.5 cm, and tend to coil at the apex. The inflorescence consists of 1–6 flowers. The flowers are nodding, elegant, and campanulate. The perianth consists of 6 tepals that are yellowish green, oblong, and 2.5 cm × 1 cm to 3.5 cm × 1.8 cm. The stamens are 1.5 cm long and the filaments are glabrous. The style is trilobed. The fruits are capsular and broadly winged. The wings are 0.8 cm wide (Figure 3.87). Medicinal uses: In China, the bulb is eaten to treat cough, bronchitis, asthma, breast cancer, lung diseases, and lack of milk. Constituents: The bulbs of Fritillaria thunbergii Miq. accumulate series of steroidal alkaloid saponins including the peimine and triterpene alkaloids verticine, verticinone, and isoverticine as well as the solanum alkaloids.393,394 Pharmacology: Peimine has been studied for its antitussive and sedative properties and verticinone isolated from Fritillaria hupehensi Hsiao & K.C. Hsia has displayed antitussive, expectorant, and antiasthmatic activities in experimental conditions, hence the medicinal uses listed above.395,396 The plant is used in a preparation known as “zhebei” that has been used in China to treat leukemia.397

145

Superorder Lilianae Takht., 1967

FIGURE 3.87  Fritillaria thunbergii Miq. CH3 N H CH3

H

H HO

H H

CH3 OH

H

H HO

H

H Verticine CH3 N

H CH3

H H

H

H H

CH3 OH

H

HO H O Verticinone

Bioresource: Anticancer alkaloid(s). The next plant discussed in this section is Hemerocallis fulva (L.) L.

146

Medicinal Plants of China, Korea, and Japan

3.2.2.1.10  Hemerocallis fulva (L.) L. [From Greek hemera = day, and kallos = beauty, and from Latin fulva = of a fulvous color, tawny] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Daylily, tawny daylily, xuan cao (Chinese), akinowasuregusa (Japanese), won chu ri (Korean), Basionym: Hemerocallis lilioasphodelus var. fulvus L. Habitat: It is a perennial herb found in the forests of China, Taiwan, India, Japan, Korea, and Russia. It is cultivated as a garden ornamental plant. Diagnosis: Hemerocallis fulva (L.) L. is 1.5 m tall. The root is fleshy and tuberous. The leaves are linear, 50–1 cm × 90–2.8 cm, and acute at the apex. The inflorescence is a cyme with 2–5 flowers. The perianth is showy, orange, and comprises a tube that is 2–4 cm long. The tepals are 5 cm × 1 cm to 12 cm × 3 cm and wavy. The filaments are 5 cm long. The anthers are purplish and 0.8 cm long. The capsules are elliptical and 2.5 × 1.5 cm (Figure 3.88). Medicinal uses: In Korea and China, the roots are used to excite the discharge of urine and to treat jaundice, hemorrhoids, and tumors of the breast. The roots are cooked with meat and eaten to strengthen the blood, to reduce fever, and to assuage toothache. The flowers are eaten to excite the discharge of urine, to assuage pains, and as a sedative. Pharmacology: An extract of Hemerocallis fulva L abrogated the survival of human colorectal carcinoma (HCT116) cells cultured in vitro.398 This is likely to be due to ­quinones, such as kwanzoquinones A–C and E, that abrogated the multiplication of human breast, central nervous system, colon, and lung cancer cells cultured in vitro with  GI50 values between 1.8 and 21.1 μg/mL.399 Note that kwanzoquinones are schistosomacidal.400

FIGURE 3.88  Hemerocallis fulva (L.) L.

147

Superorder Lilianae Takht., 1967 O

OH

O

O

OH

O OH

CH3 H3C

OH

CH3 O

OCH3

Kwanzoquinone A

O

OH

H

O

O H2N

CH3 OH

Doxorubicin

Besides, the plant contains series of glycosides of which roseoside and quercetin 3-O-beta-Dglucoside showed potent antioxidant effects.401 Moreover, an extract of the plant promoted lipolysis in adipocytes stimulated with catecholamine.402 Bioresource: In vitro pharmacological study of kwanzoquinone for its effect on cancer. The next plant discussed in this section is Lilium brownii F.E. Brown ex Miellez. 3.2.2.1.11  Lilium brownii F.E. Brown ex Miellez [After Robert Brown (1773–1858), a British botanist, librarian to Sir Joseph Banks, and from Greek lirion = a lily] History: This plant was first formally described in Cat. Expos. Soc. Hort. Lille by Auguste Miellez in 1841. Auguste Miellez (? – 1860) was a French horticulturist. Common names: Brownii Lily, ye bai he (Chinese), dang na ri (Korean). Habitat: This lily grows in grassy spots and wastelands, on hillsides, and in forests of China and Vietnam. It is also cultivated as a garden ornamental plant. Diagnosis: The bulb of Lilium brownii F.E. Brown ex Miellez is starchy, edible, milky white, smooth, globose, 4.5 cm in diameter, with lanceolate 1.8-cm-long scales. The leaves are scattered, linear, 7 cm × 1 cm to 15 cm × 2 cm, and have 5–7 nerves. The flowers are ­fragrant, massive, white, and solitary. The perianth is funnel-shaped and fragrant. The

FIGURE 3.89  Lilium brownii F.E. Brown ex Miellez.

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Medicinal Plants of China, Korea, and Japan

tepals are oblong, spreading, recurved, and 10 cm × 2 cm to 18 cm × 4.3 cm. The stamens are curved upward. The filaments are 13 cm long. The anthers are brown and conspicuous. The style is 10 cm long. The fruits are capsular and 6 cm × 3.5 cm (Figure 3.89). Medicinal uses: In China, the bulbs are used to cure fatigue and to treat lung diseases, cough, urogenital infection, deafness, indigestion, swellings, and ulcers. Constituents: The bulbs accumulate starch and steroidal saponins.403 Pharmacology: An extract of the plant impaired the enzymatic activity of monoamine oxidase B achieving an IC50 value of 0.3 μg/mL, hence the calming property mentioned above.404 Bioresource: Phytochemical and pharmacological investigations and anxiolytic agent(s). The next plant discussed in this section is Liriope graminifolia (L.) Baker. 3.2.2.1.12  Liriope graminifolia (L.) Baker [From Greek Liriope = a nymph, the mother of Narcissus, and from Latin graminifolia = with foliage-like grass] History: This plant was first formally described in Species Plantarum, Editio Secunda by Carl Linnaeus in 1762. Linnaeus (1707–1778) was a Swedish botanist. Common names: He ye shan mai dong (Chinese), maek mun dong (Korean). Basionym: Dracaena graminifolia L. Synonyms: Asparagus graminifolius L., Liriope angustissima Ohwi, Liriope crassiuscula Ohwi, Mondo graminifolium (L.) Koidz. Habitat: This perennial herb grows in the forests and grassy spots of China, Japan, and Taiwan. It is also cultivated as a garden ornamental plant. Diagnosis: The root of Liriope graminifolia (L.) Baker is tuberous. The leaves are linear, dark green, 60 × 3 cm, with 5 nerves, and serrulate at the apex. The inflorescence is a 15-cmlong spike. The flowers are arranged in clusters. The tepals are whitish, oblong, and 0.3 cm × 0.1 cm. The filaments are 0.1 cm long. The anthers are minute and light yellow. The style is 0.2 cm long. The berries are blue-black, ovoid, and minute (Figure 3.90).

FIGURE 3.90  Liriope graminifolia (L.) Baker.

149

Superorder Lilianae Takht., 1967

Medicinal uses: In China, this plant is used to cure fatigue, to treat cough, and to check hemoptysis. It is also used to excite the discharge of urine, to treat heart diseases, to stop vomiting, to break fever, to treat impotence, lack of milk, and as a laxative. Pharmacology: Note that the steroidal saponin spicatoside A isolated from Liriope platyphylla F.T. Wang & T. Tang, elicited a neurotrophic effect in rat pheochromocytoma (PC12) cells cultured in vitro.405 Besides, an extract of the roots of Liriope platyphylla F.T. Wang & T. Tang reduced the number of eosinophils in the lungs of rodents subjected to an asthma experiment on probable account of saponins such as ruscogenin glycoside isolated from Liriope muscari (Decne.) L.H. Bailey that decreased leukocyte accumulation in an animal experiment of pleurisy.406,407 H3C

O

CH3 OH

CH3

O

CH3

HO Ruscogenin

Of special interest is the fact that Liriope graminifolia (L.) Baker contains series of steroidal saponins of which methylophiopogonanone B compromised the growth of human hepatoma (SMMC-7721) and human epithelial cervical cancer (Hela) cells with IC50 values of 35 and 6 μg/mL, respectively.408 Bioresource: Phytochemical study and in vitro pharmacological study of spicatoside A for its effect on neurodegeneration. The next plant discussed in this section is Lycoris radiata (L’Hér.) Herb. 3.2.2.1.13  Lycoris radiata (L’Hér.) Herb. [From Lycoris = the name of a woman in Roman history, and radiata = radiate] History: This plant was first formally described in Sertum Anglicum by Charles Louis L’Héritier de Brutelle in 1788. Brutelle (1746–1800) was a French botanist. Common names: Spider lily, shi suan (Chinese), higan bana (Japanese). Basionym: Amaryllis radiata L’Hér. Habitat: This peculiar perennial herb is found in shady and moist spots in China, Nepal, Japan, and Korea. It is cultivated as a garden ornamental plant. Diagnosis: The bulb of Lycoris radiata (L’Hér.) Herb. is globose and 3 cm in diameter. The leaves are dark green, ligulate, 15 cm × 0.5 cm, and obtuse. The inflorescence is 30 cm long, conspicuous, fleshy, and presents a massive umbel with 4–7 flowers. The perianth is bright red. The tepals are strongly recurved, lanceolate, 3 cm × 0.5 cm, and undulate. The stamens are conspicuously exerted (Figure 3.91). Medicinal uses: In China, the bulb is applied to ulcers and inflammation of the skin and is used to treat cough. Constituents: The bulb of Lycoris radiata (L’Hér.) Herbert contains lycorine, lycorenine, and several other Amaryllidaceae alkaloids such as lycoranines A and B and galanthamine.409,410 Pharmacology: The anti-inflammatory property of the plant is most probably owed to the alkaloid lycorine.392 Lycorine inhibited the replication of the severe acute respiratory syndrome-associated coronavirus in vitro with an EC50 value of about 15.7 nM.251 Besides, lycorenine lowered blood pressure in rodents by a mechanism implying alpha-adrenoceptor

150

Medicinal Plants of China, Korea, and Japan

FIGURE 3.91  Lycoris radiata (L’Hér.) Herb.

and vagal activity.411 Moreover, lycorine, at a dose of 1 mg/kg, induced in rodents a remarkable choleretic effect.412 Furthermore, lycorine triggered apoptosis in human leukemia cells cultured in vitro and probably accounts for the cytotoxic properties reported by Son et al.413,414 Bioresource: In vitro pharmacological study of lycorine for its effect on the severe acute respiratory syndrome. The next plant discussed in this section is Ophiopogon japonicus (L. f.) Ker-Gawl. 3.2.2.1.14  Ophiopogon japonicus (L. f.) Ker-Gawl. [From Greek ophis = snake, and pogon = beard, and from Latin japonicus = from Japan] History: This plant was first formally described in Supplementum Plantarum by Linnaeus filius in 1782. filius (1741–1783) was a Swedish botanist. Common names: Mondo grass, dwarf lilyturf, fountain plant, monkey grass, mai men dong, mai dong (Chinese), ryu no hige (Japanese), so yeop maek mun dong (Korean). Basionym: Convallaria japonica L. f. Synonyms: Anemarrhena cavaleriei H. Lév., Convallaria japonica L. f.,. Convallaria japonica var. minor Thunb., Flueggea japonica (L. f.) Rich., Mondo japonicum (L.) Farw., Mondo stolonifer (H. Lév. & Vaniot) Farw., Ophiopogon argyi H. Lév., Ophiopogon chekiangensis Koiti Kimura & Migo, Ophiopogon stolonifer H. Lév. & Vaniot, Slateria japonica (L. f.) Desv. Habitat: This perennial grass grows in moist places in a geographical area covering Korea, Cambodia, Laos, Vietnam, Japan, China, and Taiwan. It is also cultivated as a garden ornamental plant. Diagnosis: The root of Ophiopogon japonicus (L. f.) Ker-Gawl. is thick, tuberous, and stoloniferous. The leaves are basal, grass-like, dark green, 10 cm × 0.2 cm to 50 cm × 0.5 cm, with 3–7 nerves, and serrulate at the margin. The inflorescence is a 5-cm–long panicle.

151

Superorder Lilianae Takht., 1967

FIGURE 3.92  Ophiopogon japonicus (L. f.) Ker-Gawl. (From Coll.: H.C. Robonson and C.B. Kloss. Ex Herb. British Museum. Sumatra, Korinchi Expedition. Loc.: Indonesia, Sumatra, Korinchi Peak. Alt.: 7300 feet. Date: April 29, 1914.)

The flowers are nodding. The tepals are whitish, lanceolate, and 0.5 cm × 0.2 cm. The filament is very short. The anthers are 0.3 cm long. The style is narrowly conical, 0.4 cm long, thick, and basally widened. The berries are glossy and bluish. The seeds are globose, numerous, and 0.8 cm in diameter (Figure 3.92). Medicinal uses: In China, this plant is used to cure fatigue, to treat cough, and to check hemoptysis. It is also used to excite the discharge of urine, to treat heart diseases, impotence, and lack of milk, to stop vomiting, to break fever, and as a laxative. Constituents: Ophiopogon japonicus (L. f.) Ker Gawl. stores a substantial amount of homoisoflavonoids and furostane saponins.415–418 Pharmacology: Homoisoflavonoids obtained from the plant inhibited the release of the inflammatory chemokine eotaxin by human bronchial epithelial (BEAS-2B) cells stimulated with interleukin-4 in vitro.419 Note that a total saponin extract of the plant attenuated the arrhythmias induced by chloroform-epinephrine, BaCl2, and aconitine, hence the cardiovascular use of the plant.420 H3C H3C

OH

HO O

CH3 H

O

H3C CH3

OH O

CH3

OH

O

O

OH

O

O

H

OH OH Ophiopogonin D

OH

OH

152

Medicinal Plants of China, Korea, and Japan

Besides, an extract of roots of Ophiopogon japonicus (L. f.) Ker Gawl. exerted a dramatic antithrombotic activity in rodents because of ruscogenin and ophiopogonin D.421 Ruscogenin isolated from the plant elicited a remarkable anti-inflammatory activity in vitro.422 Ruscogenin and ophiopogonin D displayed a potent anti-inflammatory effect in rodents and ophiopogonin D protected primary human umbilical vein endothelial cells against H2O2.423,424 A fructan isolated from the plant boosted the multiplication of lymphocytes cultured in vitro.425 Note that fatigue, cough, and blood in saliva are symptoms of tuberculosis. One might be curious to look for antimycobacterial agents in this plant. Bioresource: In vitro pharmacological study of ophiopogonin for its effect on neurodegeneration. The next plant discussed in this section is Pancratium zeylanicum L. 3.2.2.1.15  Pancratium zeylanicum L. [From Greek pan = all, and kratus = strong, and from Latin zeylanicum = from Ceylon (now Sri Lanka)] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Carl Linnaeus (1707–1778) was a Swedish botanist. Common names: Rain flower, spider white lily, Ceylon chalice lily. Habitat: It is an elegant perennial herb native to India or Sri Lanka and is cultivated as a garden ornamental or medicinal plant in many parts of Asia. Diagnosis: The bulb of Pancratium zeylanicum L. is globose, 5 cm in diameter, and develops 6–8 leaves that are linear or elliptical and 25 cm × 2 cm. The flowers are solitary, erect, showy, and pure white. The perianth is 4–5 cm long, 5 cm in diameter, and develops 12 recurved lobes. The perianth lobes are lanceolate, acuminate, and 5 cm × 1 cm. The filaments are erect and 3 cm long (Figure 3.93).

FIGURE 3.93  Pancratium zeylanicum L.

153

Superorder Lilianae Takht., 1967

Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used to treat bone injury. In Indonesia, this plant is used to break fever and to cure deafness. Pharmacology: The bulb of Pancratium zeylanicum L. probably contains a substantial amount of Amaryllidaceae alkaloids that would be worth investigating, as pancratistatin isolated from Pancratium littorale Jacq. exhibited remarkable antiviral and antineoplastic activities.340 OH OH

HO

O H O OH

NH

H

OH

O

Pancratistatin

Pancratistatin abrogated the survival of murine ovarian sarcoma (P-5076) and mouse leukemia (P388) cells cultured in vitro.340 With regard to the medicinal properties of Pancratium zeylanicum L., one could eventually speculate the involvement of Amaryllidaceae alkaloids such as lycorine in the antipyretic property of the plant.392,426 Bioresource: Phytochemical study and in vitro pharmacological study of pancrastatine for its effect on cancer. The next discussed plant in this section is Paris polyphylla Sm. 3.2.2.1.16  Paris polyphylla Sm. [From Greek Paris = the prince of Troy whose abduction of Helen provoked the Trojan War, and from Latin polyphylla = many leaved] History: This plant was first formally described in The Cyclopaedia; or, Universial Dictionary of Arts by Sir James Edward Smith in 1813. Smith (1759–1828) was a British botanist. Common names: Himalayan Paris, qi ye yi zhi hua (Chinese), jyuro (Japanese), johyu (Korean). Habitat: This strange perennial herb grows wild in the forests and streamsides of China, Bhutan, India, Laos, Burma, Nepal, Thailand, and Vietnam. It is cultivated as a garden ornamental plant. Diagnosis: Paris polyphylla Sm. is 1 m tall. The rhizome is 2.5 cm thick. The petiole is 1–5 cm long. The leaves are whorled. The blade is elliptical, 6 cm × 0.5 cm to 15 cm × 5 cm, and acute at the apex. The outer tepals are green, leaf-like, narrowly ovate, and 4.5 cm × 1 cm to 7 cm × 4 cm. The inner tepals are yellowish and linear. The filaments are 1 cm long. The anthers are 1.2 cm long. The ovary is globose, ribbed, unilocular and tuberculate. The style is short and purplish. The fruits are capsular and globose. The seeds are embedded in a red aril (Figure 3.94). Medicinal uses: In China, a very small dose of rhizomes mixed with water is ingested to cure fatigue, to expel worms from the intestine, to treat mental illnesses, epilepsy, and cancer, and as an antidote to snakebites.

154

Medicinal Plants of China, Korea, and Japan

FIGURE 3.94  Paris polyphylla Sm.

Pharmacology: The anticancer property of Paris polyphylla Sm. has been confirmed experimentally: the rhizomes abound with cytotoxic steroidal saponins that induced apoptosis of murine lung adenocarcinoma (LA795) cells cultured in vitro.427,428 Furthermore, the steroidal saponin polyphyllin D extracted from the plant impaired the proliferation of murine Lewis lung carcinoma (LL3) cells cultured in vitro.429 In addition, polyphyllin D induced apoptosis in human breast adenocarcinoma (MCF-7), human breast cancer (MDA-MB231) and human hepatocellular liver carcinoma (HepG2) cells cultured in vitro.430,431 Besides, a spirostane saponin isolated from the plant inhibited the growth of Cladosporium cladosporioides and Candida species cultured in vitro.432

H3C

O

CH3 CH3 OH O O

O OH

OH

O

H3C

OH

O O

OH OH

OH

OH Polyphillin D

CH3 O

Superorder Lilianae Takht., 1967

155

Bioresource: In vitro pharmacological study of polyphillin D for its effect on breast cancer. The next plant discussed in this section is Polianthes tuberosa L. 3.2.2.1.17  Polianthes tuberosa L. [From Latin polyanthes = several flowers, and tuberosa = tuberose] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Tuberose, sedap malam (Malay). Synonyms: Polianthes gracilis Link, Polianthes tuberosa var. plena Moldenke, Polianthes tuberosa var. gracilis (Link) Beurl. Habitat: This magnificent perennial herb is native to Mexico and is cultivated for its intense fragrance and ornamental value. Diagnosis: The rhizome of Polianthes tuberosa L. is tuberous. The leaves are 30 cm long, linear, bright green, and reddish near the base. The inflorescence is a 90-cm-long raceme with 4–6 flowers. The flowers are borne in pairs. The perianth is pure white to creamy, funnel-shaped, and produces 6 lobes. The androecium includes 6 inconspicuous stamens, the filaments of which are attached on the upper part of the perianth tube (Figure 3.95). Medicinal uses: In Cambodia, Laos, and Vietnam, the rhizomes are used to calm spasms and to treat malaria. In the Philippines, the rhizomes are boiled in water to make a liquid used to treat gonorrhea and boils. In China, the rhizomes are used for its effect on burns, infection, and swellings. The flowers are used to make perfume. Constituents: The essential oil present in the flowers contains benzyl benzoate, methyl (E)-isoeugenol, ethyl myristate, and methyl anthranilate.433 Other constituents are series of gamma unsaturated lactones.434 Pharmacology: Note that methyl anthranilate inhibited the growth of the agent of anthracnose: Colletotrichum gloeosporioides.435 Preliminary studies indicate that the plant abounds with furostane and spirostane steroidal saponins that are cytotoxic against human

FIGURE 3.95  Polianthes tuberosa L.

156

Medicinal Plants of China, Korea, and Japan

promyelocytic leukemia (HL-60) cells cultured in vitro.433,436,437 Saponins probably account for the healing and anti-inflammatory properties of the plant. Bioresource: In vitro pharmacological study of methyl anthranilate for its effect on anthracnose. The next plant discussed in this section is Polygonatum officinale All. 3.2.2.1.18  Polygonatum officinale All. [From Greek poly = many, and gony = knee, and from Latin officinale = sold as an herb] History: This plant was first formally described in Flora Pedemontana by Carlo Allioni in 1785. Allioni (1728–1804) was an Italian botanist. Common names: Lesser angular Solomon’s seal, Vietnamese coriander, yu zhu (Chinese), gak si dung gul re (Korean). Habitat: It is a peculiar perennial herb found in the forests of China, Mongolia, Taiwan, Japan, Korea, Mongolia, Russia, Vietnam, Thailand, and Europe. Diagnosis: The rhizome of Polygonatum officinale All. is terete and 1.5 cm thick. The stems are bowing, 1 m long, glabrous, and angled. The leaves are alternate. The petiole is short. The blade is glaucous below, elliptical, 5 cm × 3 cm to 20 cm × 8 cm, smooth, and acute at the apex. The inflorescence has 1–8 flowers and is axillary. The flowers are fragrant. The perianth is whitish, cylindrical, 2.5 cm long, and develops 6 lobes that are 0.3 cm long. The filaments are filiform. The anthers are minute. The ovary is 0.4 cm long. The style is 1.4 cm long. The berries are bluish, 1.2 cm in diameter, and contain 7–9 seeds (Figure 3.96). Medicinal uses: In China and Japan, the rhizomes are used to cure fatigue in tubercular patients, to treat rheumatism, to break fever, to treat cough, lung diseases, diabetes, and urogenital diseases, and as a sedative. Constituents: The plant is known to contain quercitol, flavonoids, azetidine 2-carboxylic acid, and steroidal compounds such as diosgenin.438–440 Pharmacology: The antidiabetic property of the plant is confirmed: an extract of rhizomes of Polygonatum officinale All. lowered the glycemia of normal and streptozotocin-induced diabetic rodents.441

FIGURE 3.96  Polygonatum officinale All.

157

Superorder Lilianae Takht., 1967

O

CH3

OH CH3

HO

O

H

OH CH3

Homoisoflavone

OH

H

H

HO Estradiol

A homoisoflavone isolated from the plant, triggered Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest in breast cancer cells cultured in vitro.442 Bioresource: In vitro pharmacological study of homoisoflavone for its effect on breast cancer. The next plant discussed in this section is Rohdea japonica (Thunb.) Roth. 3.2.2.1.19  Rohdea japonica (Thunb.) Roth [After Michael Rohde (1782–1812), a botanist from Bremen, and from Latin japonica = from Japan] History: This plant was first formally described in Novae Plantarum Species by Carl Peter Thunberg in 1821. Thunberg (1743–1828) was a Swedish botanist. Common names: Sacred lily, Nippon lily, wan nian qing (Chinese), omoto (Japanese). Basionym: Orontium japonicum Thunb. Synonyms: Rohdea esquirolii H. Lév., Rohdea sinensis H. Lév. Habitat: This perennial herb grows in moist places in the forests of China and Japan. It is cultivated as a garden ornamental plant. Diagnosis: The rhizome of Rohdea japonica (Thunb.) Roth is 2.5 cm thick. The leaves are dark green, cuneate, glossy, 15 cm × 2.5 cm to 50 cm × 7 cm, thickly papery, and acute at the apex. The scape grows up to 10 cm tall. The inflorescence is a spike that is suboblong, 3 cm × 1 cm to 4 cm × 1.7 cm, and densely flowered. The perianth is yellowish, 0.4 cm long, and develops 6 little thick lobes. The anthers are ovate and minute. The berries are red, globose, glossy, and 0.5 cm in diameter (Figure 3.97).

FIGURE 3.97  Rohdea japonica (Thunb.) Roth.

158

Medicinal Plants of China, Korea, and Japan

Medicinal uses: In China and Japan, the rhizomes are used to heal sores, to excite the discharge of urine, to cure fatigue, to break fever, and to soothe sore throat. O

O CH3

HO

H

CH3

H H

H3C

O

HO

O

OH

H

OH OH Rhodexin A

Pharmacology: The plant contains the cardenolide saponin rhodexin A that is cardiotonic and abrogated the growth of human erythromyeloblastoid leukemia (K562) cells cultured in vitro via apoptosis induction.443 One might be curious to study the plant further for pharmacology. Bioresource: In vitro pharmacological study of rhodexin A for its effect on human erythromyeloblastoid leukemia. The next plant discussed in this section is Sansevieria trifasciata Prain. 3.2.2.1.20  Sansevieria trifasciata Prain [After the Prince of Sanseviero (1710–1771), a learned Neapolitan, and from Latin trifasciata = ​3-banded] History: This plant was first formally described in Bengal Plants by Sir David Prain in 1903. Prain (1857–1944) was a Scottish botanist. Common names: Snake plant, mother-in-law’s tongue, lidah biawak (Malay). Synonyms: Aletris hyacinthoides var. zeylanica (L.) L., Aletris zeylanica Mill., Aloe hyacinthoides var. zeylanica L., Aloe zeylanica L., Sansevieria laurantii De Wild., Sansevieria zeylanica Willd. Habitat: This colorful perennial herb is native to Africa and is one of the most commonly grown indoor and tropical garden ornamental plants. Diagnosis: The rhizome of Sansevieria trifasciata Prain is sympodial, robust, and yellowish. The leaves are thick, vertical, linear, fibrous, fleshy, variegated, 40 cm × 2.5 cm to 150 cm × 9 cm, and channeled at the base. The inflorescence is an erect raceme that is 75 cm long. The perianth is 3 cm long, greenish-white, and scented. The tepals are linear and greenish. The stamens are 0.8 cm long and the style is 1.5 cm long. The berries are globose, 0.9 cm in diameter, orange, and contain 1–2 seeds (Figure 3.98). Medicinal uses: In Malaysia, the juice extracted from the leaves is used to alleviate earache and the leaves are boiled to make a lotion applied to itches. Constituents: The plant accumulates pregnane steroidal saponins and n-butyl-4-ol n-propyl phthalate.444–447

159

Superorder Lilianae Takht., 1967

FIGURE 3.98  (See color insert.) Sansevieria trifasciata Prain.

Pharmacology: Note that it would be worth studying the plant further as the spirostane saponins sansevistatins 1 and 2 isolated from Sansevieria ehrenbergii Schweinf. ex Baker inhibited the growth of mouse leukemia (P388) cells, Candida albicans, and Cryptococcus neoformans cultured in vitro.448 The analgesic property of the plant is confirmed: ethanol and water extracts of leaves showed remarkable analgesic effects in the acetic acid-induced abdominal writhing experiment and the formalin experiment.449 H3C

HO HO HO

O HO

O O

O

O

OH H3C HO

CH3 CH3

O HO HO

OH Pregnane saponin O OH

O O

CH3

O n-Butyl-4-ol n-propyl phthalate

O

160

Medicinal Plants of China, Korea, and Japan

Bioresource: In vitro pharmacological study of n-butyl-4-ol n-propyl phthalate for its effect on cancer. The next plant discussed in this section is Smilax calophylla Wall. 3.2.2.1.21  Smilax calophylla Wall. [From Latin smilax = bindweed, and calophylla = beautiful leaves] History: This plant was first formally described by Nathaniel Wallich. Wallich (1786–1854) was a Danish botanist. Common names: Dawi dawi, dedawi, sadawi, akar kanchil (Malay). Habitat: It is a rare climber found in the rainforests of Malaysia and Indonesia. Diagnosis: Smilax calophylla Wall. grows from a massive tuber. The leaves are lanceolate, acuminate, acute at the base, with 3 nerves, glaucous below, and 12 cm × 2.5 cm to 18 cm × 5 cm. The petiole is 0.4–0.8 cm long. The inflorescence is an umbel that is small and sessile. The male flowers are globose and yellow. The sepals are hooded and obovate. The petals are smaller than the sepals, ovate, and flat. The anthers are sessile on a disc. The fruits are drupaceous, globose, red brown, and about 1 cm in diameter (Figure 3.99). Medicinal uses: In Malaysia, the tubers are used to cure fatigue and impotence, a decoction is used as a postpartum remedy, and the leaves are applied to inflammation of the skin. Pharmacology: The male aphrodisiac property of the plant has been validated: an extract of the plant displayed some levels of androgenic property in rodents but the active component remains unveiled.450 One could suggest the involvement of steroidal saponin or a sapogenin. The anti-inflammatory property of Smilax calophylla Wall. is likely to be owed to steroidal saponins as steroidal saponins extracted from Smilax china L. inhibited the enzymatic activity of cyclooxygenase-2.451 Bioresource: Aphrodisiac agent(s). The next plant discussed in this section is Tulipa edulis (Miq.) Baker.

FIGURE 3.99  Smilax calophylla Wall. (From Coll.: C.F. Symington. Flora of the Malay Peninsula. Forest Department. Kelantan. No. 37642. Date: October 10, 1934.)

Superorder Lilianae Takht., 1967

161

3.2.2.1.22  Tulipa edulis (Miq.) Baker [From Latin tulipa = latinized version of the Turkish tulbend = a turban, and from edulis = edible] History: This plant was first formally described in Annales Museum Botanicum LugdunoBatavi by Friedrich Anton Wilhelm Miquel in 1867. Miquel (1811–1871) was a Dutch botanist. Common names: Edible tulip, lao ya ban (Chinese), san ja go (Korean). Basionym: Orithyia edulis Miq. Synonyms: Amana edulis (Miq.) Honda, Amana graminifolia (Baker ex S. Moore) A.D. Hall, Gagea argyi H. Lév., Gagea coreana H. Lév., Gagea hypoxioides H. Lév., Tulipa graminifolia Baker ex S. Moore, Tulipa minifolia Baker ex S. Moore. Habitat: This perennial herb grows on the grassy slopes and hillsides of China, Japan, and Korea. It is cultivated as an ornamental plant. Diagnosis: The bulb of Tulipa edulis (Miq.) Baker is edible, ovoid, 4 cm in diameter, and copper colored. The stems are 10–25 cm long, slender, and glabrous. The leaves are arranged in pairs, glaucous, linear, 15 cm × 5 cm to 25 cm × 10 cm, thick, and glabrous. The flowers are solitary. The pedicel is 4 cm long. The 6 tepals are whitish purple, lanceolate, and 2 cm × 0.4 cm to 3 cm × 0.7 cm. The inner stamens are slightly longer than the outer one. The filaments are glabrous and dilated at the base. The anthers are bright orange. The style is 0.4 cm long. The capsules are globose, 0.7 cm in diameter, and marked at the apex by a beak (Figure 3.100). Medicinal uses: In China, the bulbs are used to heal boils and swellings and as an antidote for snakebites. The leaves are used to heal boils, to cure diseases of the breast, and to excite the discharge of urine. In Cambodia, Laos, and Vietnam the bulbs are used to assuage toothache.

FIGURE 3.100  Tulipa edulis (Miq.) Baker.

162

Medicinal Plants of China, Korea, and Japan

Pharmacology: The pharmacological properties of members of the genus Tulipa L. have apparently been left uncared for. One could speculate that the healing and anti-inflammatory properties of Tulipa edulis (Miq.) Baker could involve steroidal saponins that are yet to be identified. Bioresource: Analgesic agent(s). The next plant discussed in this section is Veratrum nigrum L. 3.2.2.1.23  Veratrum nigrum L. [From Latin veratrum = dark roots, and nigrum = black] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Black hellebore, li lu (Chinese), cham yeo ro (Korean). Synonyms: Veratrum bracteatum Batalin, Veratrum nigrum subsp. ussuriense (Loes.) Vorosch., Veratrum nigrum var. microcarpum Loes., Veratrum nigrum var. ussuriense Loes., Veratrum ussuriense (Loes.) Nakai. Habitat: This perennial herbaceous plant is found in the forests of Kazakhstan, Mongolia, Russia, Central Europe, and China. It is cultivated as a garden ornamental plant. Diagnosis: Veratrum nigrum L. is 1 m tall. The stems are terete and stout. The leaves are cauline and sessile. The blade is broadly elliptical, 25 cm × 10 cm, glabrous, and acute at the apex. The inflorescence is a densely flowered panicle. The rachis is densely white woolly. The pedicels are 0.5 cm long and densely woolly. The tepals are black-purple, oblong, glossy, 0.8 cm × 0.3 cm, and recurved. The stamens are 0.4 cm long. The fruits are capsular and 1.5 cm × 1 cm (Figure 3.101). Medicinal uses: In Korea, the roots are used to cure nose, throat, and abdominal illnesses. In China, the roots are used to induce vomiting and to treat sore throat, bronchitis, convulsion, indigestion, and skin diseases. The roots are also used to treat aphasia arising from apoplexy, dysentery, jaundice, headache, itches, and malaria.

FIGURE 3.101  Veratrum nigrum L.

163

Superorder Lilianae Takht., 1967

Constituents: The plant contains deadly poisonous steroidal alkaloids such as germidine, germerine, verazine, jervine, and neogermbudine.452 Pharmacology: Veratrum nigrum L. contains series of steroidal alkaloids of which veratramine elicited hypotensive activity in rodents by a mechanism involving the adrenergic system.453,454 Note that veratramine is teratogenic and induces involuntary movements mediated by serotonin.455 Veratramine isolated from Veratrum dahuricum (Turcz.) Loes. inhibited the aggregation of platelets and abrogated the survival of human lung adenocarcinoma epithelial (A549), human pancreatic carcinoma (PANC-1), human pancreatic cancer (SW1990), and human lung cancer (NCI-H249) cells cultured in vitro.456,457 One might be curious to further study the plant for pharmacology.

H3C

H3C

H

HN CH3 H

CH3

H

HO

H HO Veratramine

Bioresource: In vitro pharmacological study of veratramine for its effect on pancreatic cancer. The next plant discussed in this section is Zephyranthes carinata Herb. 3.2.2.1.24  Zephyranthes carinata Herb. [From Greek Zephyrus = the god of the west wind, and anthos = flowers, and from Latin carinata = keeled] History: This plant was first formally described in Botanical Magazine by William Herbert in 1825. Herbert (1778–1847) was a British botanist. Common names: Zephyr-flower, jiu lian (Chinese). Synonyms: Amaryllis carinata (Herb.) Spreng., Amaryllis Lindleyana Schult. f., Atamosco carinata (Herb.) P. Wilson, Atamosco carinata Standl., Pogonema carinata (Herb.) Raf. Habitat: This graceful perennial herb is native to Mexico. It is cultivated as an ornamental plant all over the tropics. Diagnosis: The bulb of Zephyranthes carinata Herb. is 3 cm in diameter. The leaves are numerous, fascicled, linear, flat, and 15 cm × 0.5 cm to 30 cm × 0.8 cm. The involucres are purplish and 5 cm long. The flowers are solitary, showy, and terminal. The perianth is pink and presents 6 lobes that are obovate, 6 cm long, and acute at the apex. The perianth tube is 2.5 cm long. The stamens are slightly shorter than the perianth. The anthers are versatile and inconspicuous. The style is slender, white, and showy. The fruits are capsular and subglobose (Figure 3.102).

164

Medicinal Plants of China, Korea, and Japan

FIGURE 3.102  (See color insert.) Zephyranthes carinata Herb.

Medicinal uses: In China the bulbs are boiled in water and the liquid obtained is used to break fever. A paste of the bulbs is applied to boils. Pharmacology: The bulbs of Zephyranthes carinata Herb. store a substantial amount of Amaryllidaceae alkaloids of which pancrastitatin and 1-O-(3 hydroxybutyryl) pancratistatin were remarkably cytotoxic against human nasopharyngeal carcinoma (KB), human epithelial cervical cancer (Hela), and murine macrophage-like (P388-D1) cells cultured in  vitro.458 These alkaloids might be involved in anti-inflammatory properties of the plant.392

OH

H3C

O

OH

O

OH

O H

H

OH

NH

O OH

O

1-O-(3-hydroxybutyryl) pancratistatin

Bioresource: In vitro pharmacological study of 1-O-(3 hydroxybutyryl) pancratistatin for its effect on cancer. Cytotoxic agents are present in the next clade: the order Alismatales.

165

Superorder Lilianae Takht., 1967

3.2.3  Order Alismatales R.Br. ex Bercht. & J. Presl, 1820 The order Alismatales consists of 13 families of flowering plants of which the Alismataceae and the Hydrocharitaceae are discussed here. 3.2.3.1  Family Alismataceae Vent., 1799, nom. cons., the Water-Plantain Family The family Alismataceae consists of about 12 genera and 75 species of flowering plants best developed in the Northern hemisphere. Members of this family are aquatic herbs growing from creeping rhizomes and producing, like the Liliaceae, flavonoids and steroidal saponins. The leaves are basal, alternate, with a well-developed basally sheathing petiole and an elliptical blade showing parallel nervations. The inflorescence is a panicle or an umbel. The flowers are hypogynous, regular, and perfect. The perianth includes 3 sepals that are green and imbricate and 3 petals that are white and imbricate. The androecium consists of 6 stamens. The anthers are tetrasporangiate and dithecal. The gynoecium comprises 3 carpels arranged in a single whorl, each carpel with a terminal style and a decurrent stigma. The ovule is solitary in each carpel. The fruits are achenes. The pharmacological properties of most members of this family remain apparently insufficiently explored. Kobayashi and coworkers459 isolated the cytotoxic labdane diterpenoids chapecoderin B and C from the leaves of Echinodorus macrophyllus (Kunth) Micheli. Chapecoderins B and C exhibited cytotoxic activities against mouse lymphocytic leukemia (L1210) cells cultured in vitro with IC50 values of 7.2 and 6.0 μg/mL, respectively.460 The guaiane sesquiterpenes alismol and orientalols A and C and the germacrane sesquiterpene germacrene D extracted from Alisma orientale (Samuel) Juz. in Kom. inhibited the generation of nitric oxide by macrophages stimulated with bacterial lipopolysaccharides.461 O CH2

O CH3 CH3 HO O H3C



CH3 CH3

H CH3 Chapecoderin C

H3C



Alismol

The plant examined in this section is Alisma plantago-aquatica L. 3.2.3.1.1  Alisma plantago-aquatica L. [From Greek alisma = the ancient Greek name of the plant, and from Latin plantago = a Latin name for the plantain, and aquatica = found in the water] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Water plantain, ze xie (Chinese), saji omo daka (Japanese), jil gyeong I taek sa (Korean). Synonyms: Alisma subcordatum Raf., Alisma triviale Pursh. Habitat: This perennial herb grows in ponds, muds, swamps, and bogs and is found in China, Cambodia, Laos, Vietnam, and India. It is cultivated as an ornamental plant. Diagnosis: Alisma plantago-aquatica L. is erect and fleshy. The leaves are broadly lanceolate or elliptical and 6 cm × 2.5 cm to 10 cm × 3.8 cm. The petiole is cylindrical and 7–30 cm

166

Medicinal Plants of China, Korea, and Japan

FIGURE 3.103  Alisma plantago-aquatica L.

long. The panicle is lax and 55 cm long. The flowers are whitish and 1 cm wide. The pedicel is filiform and 2.5 cm long. The sepals are ovate, 0.3 cm long, membranaceous, and wavy. The corolla comprises 3 petals that are oblong, membranaceous, and yellowish. The filaments are 0.2 cm long. The anthers are yellow and oblong. The ovaries are ovate and 0.1 cm long. The achenes are oblong, 0.3 cm long, grooved, and pale brown (Figure 3.103). Medicinal uses: In China, this plant is used to treat dropsy, gonorrhea, diabetes, kidney disease, fatigue, and lack of milk and to abrogate fertility. In Cambodia, Laos, and Vietnam, this plant is used to excite the discharge of urine. Pharmacology: Alisma plantago-aquatica L. synthesizes a broad array of triterpenes including alisol B monoacetate, alisol B monoacetate derivatives, and sitosterol derivatives.462,463 OH O

H

H H3C

O HO

HO

OCOCH3 CH3

CH3 H

CH3

O

O

H3C

CH3

Aldosterone

Alisol B monoacetate H3C CH3 CH3

H H

H

O Progesterone

O

O

CH3 CH3

167

Superorder Lilianae Takht., 1967

Note that alisol B monoacetate isolated from Alisma orientale (Samuel) Juz. in Kom. showed immunosuppressive activity.464 Other constituents are 11-deoxyalisol C and alisol D, alisol A, alisol A monoacetate, alisol B, alisol C, and alisol C monoacetate, which showed hypocholesterolemic activities.465 Alisol A monoacetate and alisol B are the diuretic components of the plant.466 One can infer that the diuretic mechanism of action of alisols can be owed to some aldosterone antagonist effects as both types of compound are structurally similar. The same could be true for the contraceptive properties of the plant as alisols are quite close to progesterone. Alisol B 11-monoacetate displayed parasiticidal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense with IC50 values of 5.4 and 5.3 μM, respectively.467 Note that alisol B monoacetate induced apoptosis in vascular smooth muscle cells and lymphocytes cultured in vitro. Bioresource: In vitro pharmacological study of alisol B monoacetate for its effect on cancer. Cytotoxic agents are common in the next clade: the family Hydrocharitaceae. 3.2.3.2  Family Hydrocharitaceae Juss., 1789, nom. cons., the Tape-Grass Family The family Hydrocharitaceae consists of about 15 genera and 100 species of aquatic perennial herbs that are of cosmopolitan distribution. Members of this family produce proanthocyanidins and unusual series of quinones of pharmacological interest. The leaves are basal or cauline, alternate, opposite, or whorled, and sometimes developed into a blade and a petiole. The flowers are unisexual or bisexual. The inflorescence is a cyme. The perianth includes 3 distinct tepals. The androecium comprises 3–6 stamens. The anthers are tetrasporangiate, dithecal, and open by longitudinal slits. The gynoecium consists of 3–6 carpels united to form a compound, inferior, and unilocular ovary. The styles are 3–6 in number. The fruits are globose. The seeds are numerous. The pharmacological property of this family remains apparently poorly explored. Note that thalassiolin A, a glycoside flavone, isolated from Thalassia testudinum Banks & Sol. ex K.D. König inhibited the enzymatic activity of human immunodeficiency virus cDNA integrase.468 Ottelia alismoides (L.) Pers. shall be examined in this section. OH OH

OH HO HO

O

O

O

OSO3–

OH

O

Thalassiolin A

3.2.3.2.1  Ottelia alismoides (L.) Pers. [From Indian ottel-ambel = Ottelia alismoides Pers., and from Latin alismoides = Alisma-like] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Duck-lettuce, kreboboth (Malay), lung she ts’ao (Chinese), mzu ohbako (Japanese), mul jil gyeong I (Korean). Synonyms: Damasonium indicum Willd., Ottelia condorensis Gagnep., Ottelia dioecia Yan, Ottelia japonica Miq., Stratiotes alismoides L.

168

Medicinal Plants of China, Korea, and Japan

FIGURE 3.104  Ottelia alismoides (L.) Pers. (From Coll.: Marshall. Flora of Malay Peninsula. Forest Department. No. 35848. Loc: Malaysia, Tasek Bera, Pahang. March 16, 1939.)

Habitat: This aquatic weed is found in Africa, India, Malaysia, Indonesia, the Philippines, Australia, Japan, China, the Solomon Islands, and the North America. It is a common aquarium plant. Diagnosis: The root of Ottelia alismoides (L.) Pers. is fibrous. The leaves are thin, membranaceous, and light green. The petiole is 10–50 cm long, flexuous, and fleshy. The blade is submerged, elliptical, 6 cm × 5 cm to 20 cm × 16 cm, obtuse at the apex, and has 7–10 pairs of secondary nerves that are parallel and convergent. The flowers are emerged, showy, and solitary. The sepals are oblong, 1 cm long, obtuse, and persistent. The petals are membranaceous, obovate, 0.3 cm × 2.5 cm, broad, obtuse, and whitish. The androecium includes 6 stamens. The filaments are 0.4 cm long and hairy. The anthers are basifixed and linear. The gynoecium comprises 6–9 carpels. The fruits are rostrate, oblong, and 4 cm in diameter. The seeds are fusiform and 0.2 cm long (Figure 3.104). Medicinal uses: In China, this plant is reduced into a paste that is applied to abscesses of the breasts, cancer, ulcers, and burns. The leaves are used to check bleeding and as food. In the Philippines, the leaves are used to heal hemorrhoids and to break fever. Pharmacology: The anticancer property of the plant is confirmed: RPR112378 isolated from this plant compromised the polymerization of tubulin into microtubules with an IC50 value of 1.2 μM.469 In addition, otteliones A and B isolated from this plant were remarkably cytotoxic against various cancer cells cultured in vitro.470 OCH3

O

CH2

OH H

H

RPR112378

CH2

169

Superorder Lilianae Takht., 1967 CH2

O

H

CH2

CH2

H

O

H

CH2

H OCH3

OCH3 OH

OH Ottelione A

Ottelione B

In clinical trials, an extract of Ottelia alismoides (L.) Pers. treated two patients with tuberculosis of the cervical lymph gland in a period of 3 months.471 Bioresource: In vitro pharmacological study of RPR112378 and congeners for their effect on cancer and/or tuberculosis. Cytotoxic agents are common in the next clade: the superorder Ranunculanae, discussed in Chapter 4.

REFERENCES

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185

368. Ooi SO, Sim KY, Chung MC, Kon OL, 1993, Selective antiproliferative effects of thymidine. Experientia; 49(6–7):576–851. 369. Xu JP, Xu RS, Li XY., 1992, Four new cycloartane saponins from Curculigo orchioides. Planta Med; 58(2):208–210. 370. Xu JP, Xu RS, 1992, Phenyl glycosides from Curculigo orchioides. Yao Xue Xue Bao; 27(5):353–357. 371. Venkatesh P, Mukherjee PK, Kumar SN, Nema NK, Bandyopadhyay A, Fukui H, Mizuguchi H, 2009, Mast cell stabilization and antihistaminic potentials of Curculigo orchioides rhizomes. J Ethnopharmacol; 126(3):434–436. 372. Pandit P, Singh A, Bafna AR, Kadam PV, Patil MJ, 2008, Evaluation of antiasthmatic activity of Curculigo orchioides Gaertn. rhizomes. Indian J Pharm Sci; 70(4):440–444. 373. Bafna AR, Mishra SH, 2006, Immunostimulatory effect of methanol extract of Curculigo orchioides on immunosuppressed mice. J Ethnopharmacol; 104(1–2):1–4. 374. Lakshmi V, Pandey K, Puri A, Saxena RP, Saxena KC, 2003, Immunostimulant principles from Curculigo orchioides. J Ethnopharmacol; 89(2–3):181–184. 375. Wu Q, Fu DX, Hou AJ, Lei GQ, Liu ZJ, Chen JK, Zhou TS, 2005, Antioxidative phenols and phenolic glycosides from Curculigo orchioides. Chem Pharm Bull (Tokyo); 53(8):1065–1067. 376. Chauhan NS, Rao ChV, Dixit VK., 2007, Effect of Curculigo orchioides rhizomes on sexual behaviour of male rats. Fitoterapia; 78(7–8):530–534. 377. Thakur M, Chauhan NS, Bhargava S, Dixit VK, 2009, A comparative study on aphrodisiac activity of some ayurvedic herbs in male albino rats. Arch Sex Behav; 38(6):1009–1015. 378. Vijayanarayana K, Rodrigues RS, Chandrashekhar KS, Subrahmanyam EV, 2007, Evaluation of estrogenic activity of alcoholic extract of rhizomes of Curculigo orchioides. J Ethnopharmacol; 114(2):241–245. 379. Venukumar MR, Latha MS, 2002, Antioxidant activity of Curculigo orchioides in carbon tetrachloride induced hepatopathy in rats. Indian J Clin Biochem; 17(2):80–87. 380. Dias DA, Silva CA, Urban S, 2009, Naphthalene aglycones and glycosides from the Australian medicinal plant, Dianella callicarpa. Planta Med; 75(13):1442–1447. 381. Semple SJ, Pyke SM, Reynolds GD, Flower RL, 2001, In vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus. Antiviral Res; 49(3):169–178. 382. Mammone T, Muizzuddin N, Declercq L, Clio D, Corstjens H, Sente I, Van Rillaer K et al., 2010, Modification of skin discoloration by a topical treatment containing an extract of Dianella ensifolia: A potent antioxidant. J Cosmet Dermatol; 9(2):89–95. 383. Nesterov A, Zhao J, Minter D, Hertel C, Ma W, Abeysinghe P, Hong M, Jia Q, 2008, 1-(2,4-dihydroxyphenyl)3-(2,4-dimethoxy-3-methylphenyl)propane, a novel tyrosinase inhibitor with strong depigmenting effects. Chem Pharm Bull (Tokyo); 56(9):1292–1296. 384. Xu M, Zhang YJ, Li XC, Jacob MR, Yang CR, 2010, Steroidal saponins from fresh stems of Dracaena angustifolia. J Nat Prod; 73(9):1524–1528. 385. Tran QL, Tezuka Y, Banskota AH, Tran QK, Saiki I, Kadota S, 2001, New spirostanol steroids and steroidal saponins from roots and rhizomes of Dracaena angustifolia and their antiproliferative activity. J Nat Prod; 64(9):1127–1132. 386. Case RJ, Wang Y, Franzblau SG, Soejarto DD, Matainaho L, Piskaut P, Pauli GF, 2007, Advanced applications of counter-current chromatography in the isolation of antituberculosis constituents from Dracaena angustifolia. J Chromatography; 115(1–2):169–174. 387. Moharram FA, El-Shenawy SM, 2007, Antinociceptive and anti-inflammatory steroidal saponins from Dracaena ombet. Planta Med; 73(10):1101–1106. 388. Ichikawa K, Kitaoka M, Taki M, Takaishi S, IijimaY, Boriboon M, Akiyama T, 1997, Retrodihydrochalcones and homoisoflavones isolated from Thai medicinal plant Dracaena loureiri and their estrogen agonist activity. Planta Med; 63(6):540–543. 389. Isono H, 1976, Studies on the constituents of Liliaceae plants. VI, Analysis of aliphatic compounds in the leaves, stems, flowers and fruits of Erythronium japonicum Decne. Yakugaku Zasshi; 96(8):957–961. 390. Diamond KB, Warren GR, Cardellina II JH, 1985, Native American food and medicinal plants. 3. alphamethylene butyrolactone from Erythronium grandiflorum Pursh. J Ethnopharmacol; 14(1):99–101. 391. Chuah CH, Yong HS, Goh SH, 1997, Methyl eugenol, a fruit-fly attractant, from the browning leaves of Proiphys amboinensis (Amaryllidaceae). Biochem System Ecol; 25(5):391–393. 392. Yui S, Mikami M, Mimaki Y, Sashida Y, Yamazaki M, 2001, Inhibition effect of Amaryllidaceae alkaloids, lycorine and lycoricidinol on macrophage TNF-alpha production. Yakugaku Zasshi; 121(2):167–171. 393. Xue Y, Gu HL, 2005, Determination of peimine and peimine in Fritillaria thunbergii by HPLC-ELSD. Yao Xue Xue Bao; 40(6):550–552.

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394. Kitajima J, Komori T, Kawasaki T, Schulten H, 1982, Basic steroid saponins from aerial parts of Fritillaria thunbergii. Phytochem; 21(1):187–192. 395. Qian BC, Xu HJ, 1985, Studies on the antitussive and sedative activities of peimine and peimine. Yao Xue Xue Bao; 20(4):306–308. 396. Xu FZ, Zhang YH, Ruan HL, Pi HF, Chen C, Wu JZ, 2007, Preparation and antitussive, expectorant and antiasthmatic activities of verticinone-bile acids salts. Yao Xue Xue Bao; 42(3):274–278. 397. Lu D, Li D, Chen X, Ye P, Tian S, 2009, Pharmacological research of compound Zhebei granules for increasing therapeutic effect of chemotherapy in refractory acute leukemia patients. J Trad Chin Med; 29(3):190–194. 398. Kaneshiro T, Suzui M, Takamatsu R, Murakami A, Ohigashi H, Fujino T, Yoshimi N, 2005, Growth inhibitory activities of crude extracts obtained from herbal plants in the Ryukyu Islands on several human colon carcinoma cells. Asian Pac J Cancer Prev; 6(3):353–358. 399. Cichewicz RH, Zhang Y, Seeram NP, Nair MG, 2004, Inhibition of human tumour cell proliferation by novel anthraquinones from daylilies. Life Sci; 74(14):1791–1799. 400. Cichewicz RH, Lim KC, McKerrow JH, Nair MG, 2002, Kwanzoquinones A–G and other constituents of Hemerocallis fulva ‘Kwanzo’ roots and their activity against the human pathogenic trematode Schistosoma mansoni. Tetrahedron; 58(42):8597–8606. 401. Zhang Y, Cichewicz RH, Nair MG, 2004, Lipid peroxidation inhibitory compounds from daylily (Hemerocallis fulva) leaves. Life Sci; 75(6):753–763. 402. Mori S, Takizawa M, Satou M, Sakasai M, Kusuoku H, Nojiri H, Yoshizuka N, Hotta M, Kitahara T, Hase T, Takema Y, Saito M, Yada T, 2009, Enhancement of lipolytic responsiveness of adipocytes by novel plant extract in rat. Exp Biol Med (Maywood); 234(12):1445–1449. 403. Mimaki Y, Sashida Y, 1990, Steroidal saponins from the bulbs of Lilium brownii. Phytochem; 29(7):2267–2271. 404. Lin RD, Hou WC, Yen KY, Lee MH, 2003, Inhibition of monoamine oxidase B (MAO-B) by Chinese herbal medicines. Phytomed; 10(8):650–656. 405. Hur J, Lee P, Moon E, Kang I, Kim SH, Oh MS, Kim SY, 2009, Neurite outgrowth induced by spicatoside A, a steroidal saponin, via the tyrosine kinase A receptor pathway. Eur J Pharmacol; 620(1–3):9–15. 406. Lee YC, Lee JC, Seo YB, Kook YB, 2005, Liriopis tuber inhibit OVA-induced airway inflammation and bronchial hyperresponsiveness in murine experiment of asthma. J Ethnopharmacol; 101(1–3):144–152. 407. Liu J, Chen T, Yu B, Xu Q, 2002, Ruscogenin glycoside (Lm-3) isolated from Liriope muscari inhibits lymphocyte adhesion to extracellular matrix. J Pharm Pharmacol; 54(7):959–965. 408. Wang KW, Zhang H, Shen LQ, Wang W, 2011, Novel steroidal saponins from Liriope graminifolia (Linn.) Baker with anti-tumor activities. Carbohydr Res; 346(2):253–258. 409. Wu FL, Li AZ, Mao HF, 2005, Determination of galanthamine in bulb of Lycoris radiata by RP-HPLC. Zhongguo Zhong Yao Za Zhi; 30(7):523–525. 410. Wang L, Zhang XQ, Yin ZQ, Wang Y, Ye WC, 2009, Two new amaryllidaceae alkaloids from the bulbs of Lycoris radiata. Chem Pharm Bull (Tokyo); 57(6):610–611. 411. Miyasaka K, Hiramatsu Y, Takezaki T, 1979, Pharmacological studies of lycorenine, an alkaloid of Lycoris radiata herb: Vasodepressor mechanism in rodent. Jpn J Pharmacol; 29(4):605–622. 412. Cortese I, Renna G, Siro-Brigiani G, Poli G, Cagiano R, 1983, Pharmacology of lycorine. 1) Effect on biliary secretion in the rat. Boll Soc Ital Biol Sper; 59(9):1261–1264. 413. Liu XS, Jiang J, Jiaoxy, Wu YE, Lin JH, Cai YM, 2009, Lycorine induces apoptosis and down-regulation of Mcl-1 in human leukemia cells. Cancer Lett; 274(1):16–24. 414. Son M, Kim A, Lee J, Park CH, Heo JC, Lee HJ, Lee SH, 2010, Ethanol extract of Lycoris radiata induces cell death in B16F10 melanoma via p38-mediated AP-1 activation. Oncol Rep; 24(2):473–478. 415. Chang JM, Shen CC, Huang YL, Chien MY, Ou JC, Shieh BJ, Chen CC, 2002, Five new homoisoflavonoids from the tuber of Ophiopogon japonicus. J Nat Prod; 65(11):1731–1733. 416. Hoang Anh NT, Van Sung T, Porzel A, Franke K, Wessjohann LA, 2003, Homoisoflavonoids from Ophiopogon japonicus Ker-Gawler. Phytochem; 62(7):1153–1158. 417. Lin Y, Zhu D, Qi J, Qin M, Yu B, 2010, Characterization of homoisoflavonoids in different cultivation regions of Ophiopogon japonicus and related antioxidant activity. J Pharm Biomed Anal; 52(5):757–762. 418. Zhang T, Zou P, Kang LP, Yu HS, Liu YX, Song XB, Ma BP, 2009, Two novel furostanol saponins from Ophiopogon japonicus. J Asian Nat Prod Res; 11(9):824–831. 419. Hung TM, Thu CV, Dat NT, Ryoo SW, Lee JH, Kim JC, Na M, Jung HJ, Bae K, Min BS, 2010, Homoisoflavonoid derivatives from the roots of Ophiopogon japonicus and their in vitro antiinflammation activity. Bioorg Med Chem Lett; 20(8):2412–2416.

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420. Chen M, Yang ZW, Zhu JT, Xiao ZY, Xiao R, 1990, Antiarrhythmic effects and electrophysiological properties of Ophiopogon total saponins. Zhongguo Yao Li Xue Bao; 11(2):161–165. 421. Kou J, Tian Y, Tang Y, Yan J, Yu B, 2006, Antithrombotic activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents. Biol Pharm Bull; 29(6):1267–1270. 422. Huang YL, Kou JP, Ma L, Song JX, Yu BY, 2008, Possible mechanism of the anti-inflammatory activity of ruscogenin: Role of intercellular adhesion molecule-1 and nuclear factor-kappaB. J Pharmacol Sci; 108(2):198–205. 423. Kou J, Sun Y, Lin Y, Cheng Z, Zheng W, Yu B, Xu Q, 2005. Anti-inflammatory activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents. Biol Pharm Bull; 28(7):1234–1238. 424. Qian J, Jiang F, Wang B, Yu Y, Zhang X, Yin Z, Liu C, 2010, Ophiopogonin D prevents H(2)O(2)-induced injury in primary human umbilical vein endothelial cells. J Ethnopharmacol; 128(2):438–445. 425. Wu X, Dai H, Huang L, Gao X, Tsim KW, Tu P, 2006, A fructan, from Radix ophiopogonis, stimulates the proliferation of cultured lymphocytes: Structural and functional analyses. J Nat Prod; 69(9):1257–1260. 426. Li M, Wu A, Zhou P, 2006, A concise synthesis of (+)-pancratistatin using pinitol as a chiral building block. Tetrahedron Lett; 47(22):3707–3710. 427. Zhao Y, Kang LP, Liu YX, Liang YG, Tan DW, Yu ZY, Cong YW, Ma BP, 2009, Steroidal saponins from the rhizomes of Paris polyphylla and their cytotoxic activities. Planta Med; 75(4):356–363. 428. Yan LL, Zhang YJ, Gao WY, Man SL, Wang Y, 2009, In vitro and in vivo anticancer activity of steroid saponins of Paris polyphylla var. yunnanensis. Exp Oncol; 31(1):27–32. 429. Ma DD, Lu HX, Xu LS, Xiao W, 2009, Polyphyllin D elicits potent antitumour effects on Lewis cancer cells under hypoxic conditions. J Int Med Res; 37(3):631–640. 430. Cheung JYN, Ong RCY, Suen YK, Ooi V, Wong HNC, Mak TCWM, Fung KP, Yu B, Kong SK, 2005, Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells. Cancer Lett; 217(2):203–211. 431. Lee MS, Yuet-Wa JC, Kong SK, Yu B, Eng-Choon VO, Nai-Ching HW, Chung-Wai TM, Fung KP, 2005, Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft. Cancer Biol Ther; 4(11):1248–1254. 432. Deng D, Lauren DR, Cooney JM, Jensen DJ, Wurms KV, Upritchard JE, Cannon RD, Wang MZ, Li MZ, 2008, Antifungal saponins from Paris polyphylla Smith. Planta Med; 74(11):1397–1402. 433. Mimaki Y, Yokosuka A, Sakuma C, Sakagami H, Sashida Y, 2002, Spirostanol pentaglycosides from the underground parts of Polianthes tuberosa. J Nat Prod; 65(10):1424–1428. 434. Maurer B, Hauser A, 2004, Identification and synthesis of new γ-lactones from tuberose absolute (Polianthes tuberosa). Helvetica Chimica Acta; 65(2):462–476. 435. Nidiry ES, Babu CS, 2005, Antifungal activity of tuberose absolute and some of its constituents. Phytother Res; 19(5):447–449. 436. Mimaki Y, Yokosuka A, Sashida Y, 2000, Steroidal glycosides from the aerial parts of Polianthes tuberosa. J Nat Prod; 63(11):1519–1523. 437. Jin JM, Zhang YJ, Yang CR, 2004, Spirostanol and furostanol glycosides from the fresh tubers of Polianthes tuberosa. J Nat Prod; 67(1):5–9. 438. Fowden L, 1956, Azetidine-2-carboxylic acid: A new cyclic imino acid occurring in plants. Biochem J; 64:323–332. 439. Yang XG, Chen SB, Chen SL, Yang DJ, Liu TS, 2005, Studies on TLC fingerprint of flavonoids in rhizome of Polygonatum odoratum. China J Chin Mat Med; 30:104–106. 440. Okanishi T, Akahori A, Yasuda F, Takeuchi Y, Iwao T, 1975, Steroidal sapogenins of sixteen Liliaceae plants. Chem Pharm Bull; 23:575–579. 441. Kato A, Miura T, 1994, Hypoglycemic action of the rhizomes of Polygonatum officinale in normal and diabetic rodent. Planta Med; 60(3):201–203. 442. Rafi MM, Vastano BC, 2007, Identification of a structure specific Bcl-2 phosphorylating homoisoflavone molecule from Vietnamese coriander (Polygonatum odoratum) that induces apoptosis and G2/M cell cycle arrest in breast cancer cells. Food Chem; 104(1):332–340. 443. Umebayashi C, Yamamoto N, Nakao H, Toi Y, Chikahisa-Muramatsu L, Kanemaru K, Masuda T, Oyama Y, 2003, Flow cytometric estimation of cytotoxic activity of rhodexin A isolated from Rhodea japonica in human leukemia K562 cells. Biol Pharm Bull; 26(5):627–630. 444. González AG, Freire R, García-Estrada MG, Salazar A, Suárez E, 1972, New sources of steroid sapogenins-XIV: 25S-ruscogenin and sansevigenin, two new spirostan sapogenins from Sansevieria trifasciata. Tetrahedron; 28(5):1289–1297. 445. Paré JRJ, Bélanger J, Jankowski K, 1981, Asymmetric phthalate from Sansevieria trifasciata. J Nat Prod; 44(4):490–492.

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446. Mimaki Y, Inoue T, Kuroda M, Sashida Y, 1996, Steroidal saponins from Sansevieria trifasciata Phytochem; 43(6):1325–1331. 447. Mimaki Y, Inoue T, Kuroda M, Sashida Y, 1997, Pregnane glycosides from Sansevieria trifasciata. Phytochem; 44(1):107–111. 448. Pettit GR, Zhang Q, Pinilla V, Hoffmann H, Knight JC, Doubek DL, Chapuis JC, Pettit RK, Schmidt JM, 2005, Antineoplastic agents. 534. Isolation and structure of sansevistatins 1 and 2 from the African Sansevieria ehrenbergii. J Nat Prod; 68(5):729–733. 449. Anbu JS, Jayaraj P, Varatharajan R, Thomas J, Jisha J, Muthappan M, 2009, Analgesic and antipyretic effects of Sansevieria trifasciata leaves. Afr J Tradit Complement Altern Med; 6(4):529–533. 450. Nuraliza AS, Khalid BAK, Hamid A, Morat PB, Nwe KHH, 2006, Smilax calophylla overcomes the effects of adrenalectomy on the testicular 11beta-hydroxysteroid dehydrogenase activity and plasma levels of testosterone in rats. Biomed Res; 18(1):45–48. 451. Shao B, Guo H, Cui Y, Ye M, Han J, Guo D, 2007, Steroidal saponins from Smilax china and their antiinflammatory activities. Phytochem; 68(5):623–630. 452. Tezuka Y, Kikuchi T, Zhao W, Chen J, Guo Y, 1998, (+)-Verussurine, a new steroidal alkaloid from the roots and rhizomes of Veratrum nigrum var. ussuriense and structure revision of (+)-verabenzoamine. J Nat Prod; 61:1397–1399. 453. Wang L, Li W, Liu Y, 2008, Hypotensive effect and toxicology of total alkaloids and veratramine from roots and rhizomes of Veratrum nigrum L. in spontaneously hypertensive rats. Pharmazie; 63(8):606–610. 454. Wang H, Li SY, Zhao CK, Zeng X, 2009, A system for screening agonists targeting beta2-adrenoceptor from Chinese medicinal herbs. J Zhejiang Univ Sci B; 10(4):243–250. 455. Nagata R, Izumi K, Iwata S, Shimizu T, Fukuda T, 1991, Mechanisms of veratramine-induced 5-HT syndrome in mice. Jpn J Pharmacol; (1):139–146. 456. Tang J, Li HL, Shen YH, Jin HZ, Yan SK, Liu RH, Zhang WD, 2008, Antitumour activity of extracts and compounds from the rhizomes of Veratrum dahuricum. Phytother Res; 22(8):1093–1096. 457. Tang J, Li HL, Shen YH, Jin HZ, Yan SK, Liu XH, Zeng HW, Liu RH, Tan YX, Zhang WD, 2010, Antitumour and antiplatelet activity of alkaloids from Veratrum dahuricum. Phytother Res; 24(6):821–826. 458. Kojima K, Mutsuga M, Inoue M, Ogihara Y, 1998, Two alkaloids from Zephyranthes carinata. Phytochem; 48(7):1199–1202. 459. Kobayashi J, Sekiguchi M, Shigemori H, Ohsaki A, 2000, Chapecoderins A–C, new labdane-derived diterpenes from Echinodorus macrophyllus. J Nat Prod; 63(3):375–377. 460. Hagiwara H, Takeuchi F, Hoshi T, Suzuki T, Ando M, 2001, First total synthesis of chapecoderin A: Absolute configuration of the natural product. Tetrahedron Lett; 42(43):7629–7631. 461. Matsuda H, Kageura T, Toguchida I, Murakami T, Kishi A, Yoshikawa M, 1999, Effects of sesquiterpenes and triterpenes from the rhizomes of Alisma orientale on nitric oxide production in lipopolysaccharideactivated macrophages: Absolute stereostructures of alismaketones-B 23-acetate and -C 23-acetate. Bioorg Med Chem Lett; 9(21):3081–3086. 462. Chen HW, Hsu MJ, Chien CT, Huang HC, 2001, Effect of alisol B acetate, a plant triterpene, on apoptosis in vascular smooth muscle cells and lymphocytes. Eur J Pharmacol; 419(2–3):127–138. 463. Wu GP, Fukuyama Y, Rei W, Jin Xian B, Nakagawa K, 1988, An acylated sitosterol glucoside from Alisma plantago-aquatica. Phytochem; 27(6):1895–1896. 464. Zhang C, Zhou A, Zhang M, 2009, Chemical constituents of Alisma orientalis and their immunosuppressive function. Zhongguo Zhong Yao Za Zhi; 34(8):994. 465. Fukuyama Y, Pei-Wu G, Rei W, Yamada T, Nakagawa K, 1988, 11-Deoxyalisol C and alisol D: New protostane-type triterpenes from Alisma plantago-aquatica. Planta Med; 54(5):445–447. 466. Wu GP, Fukuyama Y, Yamada T, Rei W, Jin Xian B, Nakagawa K, 1988, Triterpenes from the rhizomes of Alisma plantago-aquatica. Phytochem; 27(4):1161–1164. 467. Adams M, Gschwind S, Zimmermann S, Kaiser M, Hamburger M, 2011, Renaissance remedies: Antiplasmodial protostane triterpenoids from Alisma plantago-aquatica L. (Alismataceae). J Ethnopharmacol; 135(1):43–47. 468. Rowley DC, Hansen MS, Rhodes D, Sotriffer CA, Ni H, McCammon JA, Bushman FD, Fenical W, 2002, Thalassiolins A–C: New marine-derived inhibitors of HIV cDNA integrase. Bioorg Med Chem; 10(11):3619–3625. 469. Combeau C, Provost J, Lancelin F, Tournou XY, Prod’homme F, Herman F, Lavelle F, Leboul J, Vuilhorgne M, 2000, RPR112378 and RPR115781: Two representatives of a new family of microtubule assembly inhibitors. Mol Pharmacol; 57(3):553–563.

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470. Ayyad SEN, Judd AS, Shier WT, Hoye TR, 1998, Otteliones A and B: Potently cytotoxic 4-methylene-2cyclohexenones from Ottelia alismoides. J Org Chem; 63(23):8102–8106. 471. Li H, Qu X, Zhao D, Shi Y, Guo L, Yuan Z, 1995, Preliminary study on the antitubercular effect of Ottelia alismoides (L.) Pers. Zhongguo Zhong Yao Za Zhi; 20(2):115–116.

4

Superorder Ranunculanae Takht. ex Reveal, 1992

Members of the superorders Ranunculanae and Magnolianae share an ancestor from which they have inherited the ability to accumulate isoquinoline alkaloids. The superorder Ranunculanae ­comprises the single-order Ranunculales.

4.1  ORDER RANUNCULALES JUSS. EX BERCHT. & J. PRESL, 1820 A massive body of evidence supports the fact that isoquinoline alkaloids and triterpenes are of pharmacological interest in the field of oncology, parasitology, microbiology, and cosmetology. Cytotoxic: Betulinic acid 3-beta-transcaffeate isolated from Berberis koreana Palib. (family Berberidaceae) displayed cytotoxic properties against human lung adenocarcinoma epithelial (A549), human ovary adenocarcinoma (SK-OV-3), human skin melanoma (SK-MEL-2), and human colorectal adenocarcinoma (HCT-15) cells cultured in vitro with IC50 values of 4.3, 7, 9.7, and 5.8 μM, respectively.1 The isoquinoline alkaloid racemosidine A purified from Cyclea racemosa Oliv. (family Menispermaceae) negated the proliferation of human ileocecal adenocarcinoma (HCT-8), human hepatocellular carcinoma (BEL-7402), and human ovarian carcinoma (A-2780) cells cultured in vitro with IC50 values of 2.8, 6.1, and 6.7 μM, respectively.2 The isoquinoline berberine which is common in the order Ranunculales, displayed a cytotoxic activity against human gastric carcinoma (SNU-5) cells with an IC50 value of 50 μmol/L via the induction of apoptosis.3 Antibacterial, antifungal: The isoquinolines berberine and jatrorrhizine extracted from the bark of Mahonia aquifolium (Pursh) Nutt. (family Berberidaceae) displayed antibacterial activity against Gram-negative Staphylococcus hyicus with minimum inhibitory concentrations of 25 and 250 μg/mL, respectively.4 Antiviral: Epinetrum villosum Troupin (family Menispermaceae) augments the isoquinoline alkaloid cycleanine that inhibited the replication of the human immunodeficiency virus in vitro with an IC50 value of 1.8 μg/mL.5 The isoquinoline alkaloid 1R, 1′-S-(+)-isotetrandrine obtained from the roots of Mahonia bealei (Fortune) Carrière (family Berberidaceae) protected embryo against influenza virus infection.6 Parasiticidal: The isoquinoline alkaloid berberine isolated from Arcangelisia flava (L.) Merr. (family Ranunculaceae) inhibited the growth of Plasmodium falciparum with an IC50 of 2.4 μM through a mechanism involving telomerase.7 The isoquinoline alkaloid isochondodendrine isolated from Epinetrum villosum Troupin (family Menispermaceae) showed parasiticidal activity against Plasmodium falciparum in vitro with an IC50 value of 0.2 μM.5 The isoquinoline alkaloid N-methylapateline isolated from Triclisia sacleuxii (Pierre) Diels (family Ranunculaceae) abrogated the survival of Plasmodium falciparum and Trypanosoma brucei with IC50 values of 0.9 and 1.1 μM, respectively.8 Cosmetology: Berberine derivatives significantly inhibited the enzymatic activity of elastase.9 The monoterpene carvacrol isolated from the seeds of Nigella sativa L. (family Ranunculaceae) inhibited the enzymatic activity of elastase with an IC50 value of 12 μM.10 Adonis aestivalis Link ex Webb & Berthel. (family Ranunculaceae) produces the carotenoid 191

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astaxanthin that protected dermal fibroblasts against UVA-induced gene expression of matrix-metalloproteinase at a dose of 4–8 μM.11 The phenolic cimicifugic acid I isolated from the rhizomes of Cimicifuga dahurica (Turcz. ex Fisch. & C.A. Mey.) Maxim. and Cimicifuga heracleifolia Kom. (family Ranunculaceae) inhibited the enzymatic activity of hyaluronidase with an IC50 value of 143 μM.12 The order Ranunculales comprises seven families of flowering plants including the Lardizabala­ ceae and the Ranunculaceae.

4.1.1  Family Ranunculaceae Juss., 1789, nom. cons., the Buttercup Family The family Ranunculaceae is a vast and successful clade that consists of 50 genera and 2000 species of herbs widespread in temperate and boreal regions. Ranunculaceae are often poisonous because of norditerpenoid alkaloids such as aconitine. The leaves are simple, without stipules, alternate, and variously compound or dissected. The flowers are bisexual, actinomorphic, and solitary to paniculate. The calyx comprises 3–8 sepals that are imbricate or valvate, deciduous, and sometimes petaloid. The corolla comprises many to a few free petals, mainly with a nectariferous claw, showy, yellow, white, blue, or pink. The stamens are numerous, spirally arranged and centripetal, free, distinct, and with long and thin filaments. The gynoecium consists of many free carpels. Each carpel develops a style. The placentation is marginal or basal. The fruits are follicles, achenes, or berries. Classical examples of Ranunculaceae are Ranunculus acris L. (buttercup) and the ornamental Aquilegia vulgaris L. (European columbine) and Helleborus orientalis Lam. (lenten rose). In ancient times, decoctions of Ranunculus were used to make arrow poison, to punish criminals, and to bring  to death elders with incurable and painful diseases. Dioskurides (first century AD) noted “Ranunculus . . . of this there are many kinds, but ye faculty is one, sharp and too much exulcerating.” A large number of Ranunculaceae are irritant on account of a glycoside called ranunculin that readily breaks down in bruised plant tissue by enzyme action to release protoanemonin that is a volatile, strongly irritant, and unstable terpenoid lactone. Pulsatilla (British Pharmaceutical Codex, 1934) consists of the dried Anemone pulsatilla L. (Pulsatilla vulgaris Mill.) that contains anemonin. Pulsatilla is a local irritant and it has been used for its supposed value in dysmenorrhea and amenorrhea, as a liquid or a tincture.

O

O

O

O Anemonin H3CO

OH H

O

H3CO N

O O

H3C O

CH3

H

H3CO

H H

OCH3 Delphinine

193

Superorder Ranunculanae Takht. ex Reveal, 1992 O N

O H

CH3

H O

H3CO OCH3

O

Hydrastine

Other notorious toxic agents of Ranunculaceae are diterpene alkaloids, isoquinoline alkaloids, and cardiac glycosides. Diterpenes: Examples of ranunculaceous diterpene alkaloids are aconitine, elatine, and delphine. The dried roots of Aconitum napellus L. (wolfsbane root), containing not less than 0.5% alkaloids calculated as aconitine (Aconite, British Pharmaceutical Codex, 1963), were formerly used as tinctures in the early stages of fever and as liniments in the treatment of neuralgia, sciatica, and rheumatism, but have been dropped because of excessive toxicity. Oral intake of aconitine is shortly followed by tingling of the tongue, mouth, stomach, and skin followed by numbness, anesthesia, nausea, vomiting, diarrhea, excessive salivation, incoordination, muscular weakness, vertigo, and death from paralysis of the heart or the respiratory center. The diterpene alkaloid elatine, obtained from Delphinium elatum L., has been used to relax skeletal muscles similar to tubocurarine at a dose of 10 mg, three to five times daily. Staphisagria (British Pharmaceutical Codex, 1949) consists of the dried ripe seeds of Delphinium staphisagria L. containing 1% of alkaloids, including delphinine. It has been used to treat lice infestation. Isoquinoline alkaloids: Classical examples of ranunculaceous isoquinoline alkaloids are hydrastine and berberine. Hydrastis (British Pharmaceutical Codex, 1949) consists of the dried rhizomes and roots of Hydrastis canadensis L. (golden seal) containing not less than 1.5% of hydrastine. It has been used to stop excessive uterine hemorrhage and as a bitter stomachic. Hydrastine hydrochloride (British Pharmaceutical Codex, 1949) constricts peripheral vessels and causes uterine contraction and arrests uterine hemorrhage. It has been used at a dose of 15–60 mg, but it is of doubtful value. Hydrastis canadensis L. contains berberine that is antibacterial, fungicidal, and antiprotozoal and decreases intestinal peristalsis. Cardiac glycosides: Hellebore (British Pharmaceutical Codex, 1934) consists of the dried rhizomes and roots of Helleborus niger L. (Christmas rose) that contains cardiac glycosides of the bufadienolide type including helleborin, helleborein, and hellebrin. Hellebrin has strophantin-like action and has been used as a cardiotonic. The aerial parts of Adonis vernalis L. (Adonis, French Pharmacopoeia, 1965) have been used instead of Digitalis as a tincture (1 in 10, dose 10–30 minims). Adonis contains a number of cardenolides among which cymarin is the chief active constituent. Aconitum fischeri Rchb. is the first plant examined in this section. 4.1.1.1  Aconitum fischeri Rchb [From Latin aconitum = unconquerable poison and after Friedrich Ernst Ludwig Fischer (1782–1854), Russian botanist, born in Germany. He was the director of the St Petersburg botanical garden]

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History: This plant was first formally described in Monographia Generis Aconiti by Ludwig Reichenbach in 1820. Reichenbach (1793–1879) was a German botanist. Common names: Fischer monkshood, American aconite, bao ye wu tou (Chinese), ki da ri ba kkot (Korean). Habitat: It is a large perennial herb found in the moist grasslands of China, Korea, and Russia. It is cultivated as an ornamental plant for gardens. Diagnosis: The stems of Aconitum fischeri Rchb. are erect, 1 m tall, hairy, and support 20 leaves. The petiole is 6.5–10 cm long and hairy. The blade is 8 cm × 12 cm to 12 cm × 15 cm and deeply incised. The inflorescence is terminal and has 4–6 flowers. The sepals are purplish blue. The lower sepals are 1 cm long, the lateral sepals are 2 cm long, and the upper sepal is 2.5 cm long and shortly beaked. The petals are glabrous. The limb is 0.8 cm long. The lip is 0.45 cm long and bifid at the apex. The spur is ­circinate and 0.2 cm long. The stamens are glabrous. The gynoecium consists of 3 hairy carpels. The follicles are 1.5 cm long and glabrous. The seeds are 0.25 cm long (Figure 4.1). Medicinal uses: In China, this plant is used to treat colds, fatigue, lumbago, and small pox. It is also used to heal ulcers and for abortions. Constituents: Aconitum fischeri Rchb. is likely to produce aconitine. Note that aconitine-type norditerpenoid alkaloids, 6-dehydroacetylsepaconitine and 13-hydroxylappaconitine, along with norditerpenoid alkaloids, lycoctonine, delphatine, and lappaconitine, have been isolated from the roots of Aconitum heterophyllum Wall.13 Pharmacology: The abortive effect of Aconitum fischeri Rchb. could be mediated by aconitine and congeners.14 Besides, aconitine and derivatives exhibited remarkable anti-­ inflammatory and analgesic effects in several experiments.15 Aconitine has also been used therapeutically as a treatment for pain and inflammation.16 Note that a tincture of Aconitum napellus L. has been used to treat cough and fever in Europe, hence the use of Aconitum fischeri Rchb to treat colds.

FIGURE 4.1  Aconitum fischeri Rchb. (From Plantae Vasculares Orientis Extremi Rossici. Loc.: Russia, Khabarovskiy territory.)

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Superorder Ranunculanae Takht. ex Reveal, 1992 OH

OCH3

OCH3

O

H3C

OH

N

O

OCOCH3

HO OCH3 H3CO

Aconitine

Bioresource: Anticancer norditerpenoid alkaloid(s). The next plant discussed in this section is Anemone chinensis Bunge. 4.1.1.2  Anemone chinensis Bunge [From Greek anemos = wind, and from Latin chinensis = from China] History: This plant was first formally described in Mémoires de l’Académie Imperiale des Sciences de St.-Pétersbourg by Alexander Georg von Bunge in 1832. Bunge (1803–1890) was a Russian botanist. Common names: Wind flower, bai tou weng (Chinese), jung guk hal mi kkot (Korean). Synonym: Pulsatilla chinensis (Bunge) Regel. Habitat: It is a perennial rhizomatous herb found in the forests and grasslands of China, Korea, and Russia. Diagnosis: Anemone chinensis Bunge is 35 cm tall. The petiole is 7–15 cm long and hairy. The blade is 4.5 cm × 6.5 cm to 14 cm × 16 cm, foliolate, hairy, and toothed. The scape is 20 cm tall and puberulent. The sepals are violet, erect, oblong, 4.5 cm × 2 cm, and puberulent. The stamens are half as long as the sepals. The anthers are yellow. The infructescence is 12 cm in diameter. The achenes are 0.5 cm long, flattened, and puberulent. The follicles are 6.5 cm long and woolly (Figure 4.2). Medicinal uses: In China, this plant is used to treat dysentery, malaria, hemorrhoids, diarrhea, gonorrhea, skin infection, stomach and uterine discomforts, vermin infestation, and to excite the discharge of urine. Pharmacology: Anemone chinensis Bunge contains betulinic acid that inhibited the replication of the hepatitis B virus cultured in vitro.17 The antimalarial property of this plant is confirmed as betulinic acid showed an antiplasmodial property against Plasmodium CH2 H3C

CH3

CH3

COOH CH3

HO H3C

CH3 Betulinic acid

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Medicinal Plants of China, Korea, and Japan

FIGURE 4.2  Anemone chinensis Bunge.

falciparum.18 Betulinic acid is known to be a broad spectrum cytotoxic triterpene in vitro, hence the antiamoebic use of the plant.19 In fact, betulinic acid obtained from Bertholletia excelsa Bonpl. (order Lecythidales, family Lecythidaceae) stem bark showed significant in vitro trypanocidal activity against Trypanosoma cruzi.20 In addition, Anemone chinensis Bunge contains series of hederagenin and oleanane saponins that may account for the antibacterial property mentioned above.21 An extract of saponins from the roots showed immunostimulating property in rodents.22 Bioresource: In vitro pharmacological study of betulinic acid derivatives for their effects on cancer. Saponins abound in Cimicifuga foetida L., discussed next. 4.1.1.3  Cimicifuga foetida L. [From Latin cimex = bug, fugo = to drive away, and foetida = evil smelling] History: This plant was first formally described in Systema Naturae by Carl Linnaeus in 1767. Linnaeus (1707–1778) was a Swedish botanist. Common names: Fetid bugbane, sheng ma (Chinese), hwang sae seung ma (Korean). Habitat: It is a tall herb found in the forests, riverbanks, and meadows of China, Korea, Bhutan, India, Kazakhstan, Mongolia, Burma, and Russia. Diagnosis: The rhizome of Cimicifuga foetida L. is robust and blackish. The stems are 2 m tall, branched, and hairy. The leaves are pinnate. The petiole is 15 cm long. The blade is triangular and 30 cm wide. The terminal leaflet is rhombic, 2.5 cm × 10  cm to 1  cm × 5 cm, lobed, and serrate. The lateral leaflets are obliquely ovate. The distal cauline leaves are sessile and small. The inflorescence is a spike. The flowers are 0.5 cm in diameter and innumerable. The sepals are white, obovate, and 0.5 cm long. The petals are broadly elliptical, 0.3 cm long, and thin. The stamens are 0.5 cm long. The anthers are yellow. The gynoecium consists of 2–5

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Superorder Ranunculanae Takht. ex Reveal, 1992

FIGURE 4.3  Cimicifuga foetida L.

carpels that are hairy and sessile. The follicles are oblong, 1 cm × 0.25 cm to 1.5  cm × 0.5 cm, and hairy. The seeds are brown, elliptical, minute, and covered with scaly wings (Figure 4.3). Medicinal uses: In China, the rhizomes are used to promote digestion, to mitigate headache, to soothe sore throat, and to treat scarlet fever, dysentery, measles, small pox, fever, poisoning, ulcers, typhoid fever, and tonsillitis. Pharmacology: An extract of Cimicifuga foetida L. exhibited cytotoxic activities against human hepatocellular liver carcinoma (HepG2) cells and normal mouse hepatocytes cultured in vitro with IC50 values of 21 and 80 μg/mL, respectively, on probable account of saponins.23 In fact, the rhizomes contain series of cycloartane saponins with anticomplement, immunosuppressive, and cytotoxic activities against Ehrlich’s ascites carcinoma, breast cancer, and human hepatocellular liver carcinoma (HepG2) cells cultured in vitro.24−29 CH3 OH

H3C CH3 CH3

O O H3C

CH3 O

H HO

OH OH

O OH OH

CH3 OH

CH3 OH

CH3

O

H OH Astragaloside IV

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Medicinal Plants of China, Korea, and Japan

Note that cycloartane triterpenes are anti-inflammatory and may account for the anti-inflammatory use of the plant.30 One such cycloartane is astragaloside IV isolated from Astragalus membranaceus Bunge (order Fabales, family Fabaceae) that protected rodents against airway hyper-responsiveness in the ovalbumin aerosol experiment.31 One might be curious to identify anti-inflammatory cycloartane in Cimicifuga foetida L. Bioresource: In vitro pharmacological study of astragaloside IV for its effect on allergies. Triterpene saponins are found in Clematis chinensis Osbeck, discussed next. 4.1.1.4  Clematis chinensis Osbeck [From Greek clematis = long, lithe branches, and from Latin chinensis = from China] History: This plant was first formally described in Dagbok ofwer en Ostindisk Resa by Pehr Osbeck in 1757. Osbeck (1723–1805) was a Swedish explorer and naturalist. Common names: Chinese clematis, wei ling xian (Chinese). Synonym: Clematis benthamiana Hemsl. Habitat: It is a deciduous woody climber found in the forests of China, Taiwan, Japan, and Vietnam. Diagnosis: The stems of Clematis chinensis Osbeck are longitudinally grooved. The leaves are pinnate and pentafoliolate. The petiole is 1.5–7.5 cm long. The leaflets are lanceolate, 1.5 cm × 1 cm to 9.5 cm × 6.5 cm, papery, round at the base, and attenuate at the apex. The cyme is axillary. The flowers are 1.5–2.5 cm in diameter. The calyx comprises 4 sepals that are pure white, spreading, oblong, 0.5 cm × 0.1 cm to 2 cm × 0.5 cm, and acute at the apex. The stamens are 0.5 cm long. The anthers are narrowly oblong and 0.25 cm long. The ovaries are hairy. The style is 0.5 cm long and densely hairy. The achenes are elliptical and 0.5 cm long (Figure 4.4). Medicinal uses: In China, this plant is used to treat malaria, rheumatism, jaundice, alcoholism, dropsy, and cough. It is also used to excite the discharge of urine, to induce menses, to check internal hemorrhages, and as a laxative. In Taiwan, this plant is used to assuage

FIGURE 4.4  Clematis chinensis Osbeck. (From Arnold Arboretum, Harvard University. Herbarium. No. 3471. Herbarium of the University of Amoy. Flora of Fukien, China. Loc.: China, Yenping, in thickets.)

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headache and to break fever. In Cambodia, Laos, and Vietnam, this plant is used to excite the discharge of urine, to treat indigestion, and to induce menses. Pharmacology: An extract of Clematis chinensis Osbeck lowered the blood pressure of  rodents through a mechanism involving histamine, hence the use of the plant to treat headache.32 Are saponins involved here? A saponin extract of the plant exhibited cytotoxic activities against Ehrlich’s ascites carcinoma, murine ascite sarcoma (S180A), and murine hepatoma (Hepa) cells cultured in vitro with IC50 values of 242, 193, and 130 μg/mL, respectively, and impaired the growth of transplanted mouse tumor (S180) in vivo.33 The triterpene saponin clematochinenoside C isolated from the plant inhibited the enzymatic activity of cyclooxygenase-1 and cyclooxygenase-2 with IC50 values of 6.3 and 6.1 μM, respectively.34 Another saponin isolated from the plant displayed anti-inflammatory and antirheumatoid effects in rodents, hence the use of the plant to treat rheumatism.35 This plant contains oleanane saponins, oleanolic acid, and hederagenin.36,37 Oleanolic acid isolated from Nauclea orientalis (L.) L. (order Gentianales, family Rubiaceae) displayed a modest antiplasmodial property against Plasmodium falciparum and protected rodents against CCl4, acetaminophen, and cadmium chloride-induced liver insults.38,39 H3C

CH3

CH3

CH3

COOH CH3

HO H3C

CH3 Oleanolic acid

Bioresource: In vitro pharmacological study of oleanolic acid derivatives as anticancer agents. Oleanolic acid is also known to be anti-inflammatory, antihyperlipidemic, and antitumorpromotion.40 Anemonin could be involved as well in the anti-inflammatory property of the plant; this shall be discussed further for the next plant Clematis gouriana Roxb. ex DC. 4.1.1.5  Clematis gouriana Roxb. ex DC. [From Greek clematis = long, lithe branches, and after Gourian?] History: This plant was first formally described in Regni Vegetabilis Systema Naturale by Augustin Pyramus de Candolle in 1817. de Candolle (1778–1841) was a Swiss botanist. Common names: Gourian clematis, xiao suo yi teng (Chinese). Synonyms: Clematis martini H. Lév., Clematis vitalba subsp. gouriana (Roxb. ex DC.) Kuntze, Clematis vitalba L. var. gouriana (Roxb. ex DC.) Finet & Gagnep., Clematis vitalba var. micrantha H. Lév. & Vaniot. Habitat: It is a deciduous woody climber found in the forests of China, Bhutan, India, Burma, Nepal, Papua New Guinea, and the Philippines. It is grown as an ornamental plant. Diagnosis: The stem of Clematis gouriana Roxb. ex DC. is longitudinally grooved, puberulous, and grows up to a length of 5 m. The leaves are pentafoliolate. The petiole is 1–10 cm long.

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Medicinal Plants of China, Korea, and Japan

The leaflets are ovate, 2.5 cm × 1.5 cm to 10.5 cm × 5.5 cm, thin, round at the base, and acuminate at the apex. The inflorescence is a densely flowered cyme. The flowers are 0.7–1 cm in diameter and pure white. The calyx consists of 4 sepals that are white, spreading, ovate, 0.5 cm × 0.2 cm, and obtuse at the apex. The androecium is showy and consists of 0.5-cmlong stamens. The anthers are minute. The ovaries are hairy. The style is 0.3 cm long and densely hairy. The achenes are lanceolate, minute, and develop 2-cm-long tails (Figure 4.5). Medicinal uses: In China, Cambodia, Laos, and Vietnam, this plant is used to break fever and to excite the discharge of urine. In Taiwan, this plant is used to heal wounds, to counteract snakebites, and to break fever. In Cambodia, Laos, and Vietnam, this plant is used to cure fatigue, allergies, and as a laxative. It is also used to treat goiter and indigestion. Pharmacology: Apparently unknown. Note that several members of the genus Clematis L. are used to treat inflammation and fever. For instance, Clematis vitalba L. extracts displayed anti-inflammatory activity in the carrageenan-induced paw edema experiment on probable account of vitalboside that elicited dramatic anti-inflammatory and analgesic activities in several experiments of inflammation, pain, and fever.41 O

OH

HO HO

O

O

OH H

OH

OH

O

OH Vitalboside

Bioresource: Pharmacological study of vitalboside for its effect on skin ageing. Another possible anti-inflammatory agent involved here could be anemonin, as anemonin isolated from Clematis crassifolia Benth. inhibited the generation of nitric oxide by macrophages

FIGURE 4.5  Clematis gouriana Roxb. ex DC. (From Singapore Botanic Gardens.)

Superorder Ranunculanae Takht. ex Reveal, 1992

201

stimulated with bacterial lipopolysaccharides.42 Note that anemonin is acrid and could account for the rubefacient and cathartic properties mentioned above. The plant may augment some ­alkaloids of pharmacological interest. This is exemplified with Coptis chinensis Franch., discussed next. 4.1.1.6  Coptis chinensis Franch. [From Greek kopto = to cut, and from Latin chinensis = from China] History: This plant was first formally described in Journal de Botanique by Adrien René Franchet in 1897. Franchet (1834–1900) was a French botanist. Common names: Chinese goldthread, huang lian (Chinese). Habitat: This perennial herb is found in the bogs and forests of China. It is cultivated as an ornamental plant. Diagnosis: The rhizome of Coptis chinensis Franch. is bright yellow inside. The petiole is 5–15 cm long and glabrous. The blade is ovate, dull dark green, 5 cm × 5 cm to 10 cm × 10 cm, trilobed, dissected, thin, and cordate at the base. The lateral lobes are obliquely ovate. The central lobe is rhombic, 3–8 cm long, deeply 3–5 lobed, serrate, and acute at the apex. The inflorescence is 10–25 cm long, glabrous, fleshy, angled, and has 3–8 flowers. The sepals are greenish, lanceolate, 0.6 cm × 0.2 cm to 1.2 cm × 0.3 cm, and glabrous. The petals are lanceolate, 0.5 cm long, glabrous, and attenuate at the apex. The stamens are 0.4 cm long. The gynoecium consists of 8–12 carpels. The follicles are 0.5–1 cm long. The seeds are minute (Figure 4.6). Medicinal uses: In China, this plant is used to break fever, to stop nausea, to check hemorrhages and to treat inflammation of the eyes, lack of milk, boils, inflamed intestines,

FIGURE 4.6  Coptis chinensis Franch.

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Medicinal Plants of China, Korea, and Japan

diabetes, and indigestion. In Cambodia, Laos, and Vietnam, this plant is used to treat urogenital infections, aphthae, and inflammation of the eyes, and to induce menses. Pharmacology: The antidiabetic property of Coptis chinensis Franch. is confirmed: an extract of the plant protected rodents from alloxan-induced diabetes.43 O O

N+ OCH3

OCH3 Berberine

Besides, this plant accumulates a substantial amount of the alkaloid berberine that inhibited the enzymatic activity of monoamine oxidase A achieving an IC50 value of 126 μM.44 Berberine is a well-known antibacterial agent that has the potential to restore the effectiveness of beta-lactam antibiotics against methicillin-resistant Gram-positive Staphylococcus aureus, hence the use of the plant in treating inflammation of the eyes, boils, infected genitals, and aphthae.45 The use of the plant to treat inflamed intestines has been confirmed: an extract of the plant displayed analgesic activity in neonatal maternal separation-induced visceral hyperalgesia in rats.46 In addition, berberine and total alkaloids isolated from this plant protected rodents against aluminum-induced brain damage.47 Moreover, berberine can efficiently inhibit the proliferation of human erythromyeloblastoid leukemia (K562) and human histiocytic lymphoma (U937) cells, via apoptosis induction.48,49 Furthermore, a total alkaloid extract of the plant abrogated the formation of ulcers induced by acetic acid in rodents.50 Bioresource: Pharmacological treatment of berberine and derivatives for their effect on cancer. Cytotoxicity has been observed in Paeonia lactiflora Pall., discussed next. 4.1.1.7  Paeonia lactiflora Pall. [After Paeon = the physician of the gods in Homer’s Iliad who used the plant to heal the wound that Hercules inflicted on Pluto, and from Latin lactiflora = with milky white flowers] History: This plant was first formally described in Reise durch Verschiedene Provinzen des Russischen Reichs by Peter Simon Pallas in 1776. Pallas (1741–1811) was a German botanist. Common names: Chinese peony, shao yao (Chinese), ebisugusuri (Japanese). Synonyms: Paeonia albiflora Pall., Paeonia albiflora Pall. var. trichocarpa Bunge, Paeonia chinensis L. Vilmorin, Paeonia lactiflora var. trichocarpa (Bunge) Stern, Paeonia lactiflora var. villosa M.S. Yan & K. Sun, Paeonia sinensis Steud., Paeonia yui W.P. Fang. Habitat: This perennial herb is found in the forests of China, Japan, Korea, Mongolia, and Russia. It is native to Manchuria and Mongolia. It is widely cultivated as an ornamental plant. Diagnosis: Paeonia lactiflora Pall. is 1 m tall. The root is thick. The stems are glabrous. The leaves are compound. The leaflets are lanceolate, 4.5 cm × 1.5 cm to 15 cm × 5 cm, and acuminate at the apex. The flowers are massive, solitary, and 10 cm wide. The calyx ­consists of 3 or 4 sepals that are broadly ovate and 1 cm × 1 cm to 1.5 cm × 2 cm. The corolla comprises 9–15 petals that are white or pink, membranaceous, obovate, and 3.5 cm × 1.5 cm to 5.5 cm × 4.5 cm. The filaments are yellow and 1 cm long. The anthers

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203

are yellow and conspicuous. The gynoecium consists of 2–5 carpels that are green purple. The follicles are elliptical and 2.5 cm × 1 cm to 3 cm × 1.5 cm (Figure 4.7). Medicinal uses: In China, this plant is used to stimulate the circulation of blood, to excite the discharge of urine, to treat fatigue, cholera, tuberculosis, eye diseases, indigestion, liver diseases, lumbago, and skin infection. Pharmacology: The hepatoprotective property of Paeonia lactiflora Pall. is confirmed: an extract of the plant protected rodents against d-galactosamine-induced hepatocellular damage.51 The hemodynamic property of the plant is confirmed: Paeonia lactiflora Pall. is known to promote blood circulation, to discard blood stasis, to inhibit the aggregation of platelets, to increase fibrinolytic activity, and to promote thrombolysis.52 In addition, an extract of the roots triggered the vasodilation of rat aorta exposed to prostaglandin F2.53 Paeoniflorin and 8-debenzoylpaeoniflorin extracted from this plant lowered the glycemia of streptozotocin-induced diabetic rodents.54 Besides, paeoniflorin induced a dramatic fall in the cholesterol level in hyperlipidemic rodents.55 Moreover, a derivative of albiflorin isolated from this plant significantly increased the enzymatic activity of alkaline phosphatase of mouse preosteoblastic (MC3T3–E1) cells.56 An extract of the plant elicited antidepressant effects in the forced swimming and tail suspension experiments because of glycosides such as aspaeonilactone-C and benzoylpaeoniflorin.57−59 Note that an extract of Paeonia lactiflora Pall. inhibited spontaneous firing activity in the cerebral cortical neurons in rodents.60 An extract of the roots abrogated the survival of human hepatocellular liver carcinoma (HepG2) cells via apoptosis induction on probable account of stilbenes.61

FIGURE 4.7  Paeonia lactiflora Pall.

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Medicinal Plants of China, Korea, and Japan OH CH3

O OH

O

O

OH OH

O

H2C

OH

OH

O O

OH HO Paeoniflorin

Trans-resveratrol

Trans-resveratrol isolated from the plant abrogated the survival of human hepatocellular liver carcinoma (HepG2) and human colon cancer (HT–29) cells with IC50 values of 11.8 and 25.2 μg/ mL, respectively. In addition, trans-epsilon-viniferin and cis-viniferin and gnetin H exhibited dramatic cytotoxic activities against human epithelial cervical cancer (Hela) and human breast adenocarcinoma (MCF–7) cells cultured in vitro.62 Stilbenes are probably involved in the cytotoxic and apoptotic effect of an extract of the plant against human bladder cancer (TSGH-8301) cells cultured in vitro.63 Trans-epsilon-viniferin and gnetin H significantly inhibited 2-deoxyribose degradation and lipid peroxidation in rat liver microsomes.64 Bioresource: Stilbenoid(s) of anticancer pharmacological value and in vitro pharmacological study of paeoniflorin for its effect on diabetes. This plant contains the hydrolysable tannin 1,2,3,4,6-penta-O-galloyl-beta-d-glucose that inhibited the replication of the hepatitis B virus cultured in vitro.65 This tannin is found in Paeonia ­suffruticosa Andrews, discussed next. 4.1.1.8  Paeonia suffruticosa Andrews [After Paeon = the physician of the gods in Homer’s Iliad who used the plant to heal the wound that Hercules inflicted on Pluto, and from Latin suffruticosa = bushy] History: This plant was first formally described in Botanist’s Repository for New and Rare Plants by Henry Charles Andrews, in 1804. Andrews (1794–1830) was a British botanist. Common names: Tree peony, mu dan (Chinese), hatsugarasu (Japanese). Synonym: Paeonia moutan Sims. Habitat: It is a deciduous shrub found in the forests of China. It is cultivated as an ornamental plant for gardens. Diagnosis: Paeonia suffruticosa Andrews is 1.5 m tall. The stems are brown gray. The proximal leaves are compound. The leaflets are ovate and 4.5 cm × 2.5 cm to 10 cm × 7 cm. The terminal leaflets are trilobed. The lateral leaflets are entire or lobed. The flowers are solitary, massive, terminal, and 15 cm in diameter. The corolla comprises 5–11 petals that are white, ovate, 8 cm × 5 cm, and incised at the apex. The filaments are pink and 1 cm long. The anthers are elliptical and 0.5 cm long. The gynoecium consists of 5 carpels that are densely tomentose. The stigmas are red. The follicles are oblong, brown, and tomentose (Figure 4.8). Medicinal uses: In China, this plant is used to treat scarlet fever, convulsion, hemorrhages, bleeding, and as a sedative.

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FIGURE 4.8  Paeonia suffruticosa Andrews.

Pharmacology: The styptic and anti-inflammatory properties of the plant are most probably to the result of hydrolyzable tannins. Suffruticosides A, B, C, and D, galloyl-oxypaeoniflorin and galloyl-paeoniflorin extracted from Paeonia suffruticosa Andrew exhibited remarkable radical scavenging properties in vitro.66 Besides, the hydrolyzable tannin 1,2,3,4,6-penta-O-galloyl-beta–d-glucose, a major component of the roots was found to inhibit the growth of human hepatocellular carcinoma (SK-HEP-1) cells cultured in vitro.67 OH HO

OH

OH

OH

HO

OH O

O H

HO O

H O

O O

O

O

H

H3C

O

H

HO

OH

H

O

O

OH

O

OH

HO OH

OH OH

1,2,3,4,6-Penta-O-galloyl-beta-D-glucose

OCH3 Paeonol

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In addition, 1,2,3,4,6-penta-O-galloyl-beta-d-glucose exhibited dramatic antioxidant, antimutagenic, neuroprotective, vasorelaxant, and anti-inflammatory properties.68,69 Paeonol, another major component of the plant, inhibited the aggregation of platelets, scavenged free radicals, and reduced cerebral infarct and neurodeficit in rodents.70 The plant contains paeonol that protected rodents against beta-amyloid-induced neurodegeneration.71 Besides, paeonol showed significant in vitro antidiabetic effects by hampering glucose uptake by intestinal brush-border membrane vesicles and stimulating glucose uptake into human foreskin fibroblast (Hs68) and mouse embryonic fibroblast (3T3–L1) cells.72 Note that glycosides may be responsible for the calming effect of the plant as a total glycoside extract of Paeonia lactiflora Pall. was antidepressant in the chronic unpredictable stress experiment.73 Moreover, glycosides may contribute to the antipyretic property of the plant as sulprostone-induced fever was blocked by pretreatment of total glucosides of Paeonia lactiflora Pall.74 Bioresource: In vitro pharmacological study of paeonol for its effect on neurodegeneration. Ranunculus sceleratus L. is described next. 4.1.1.9  Ranunculus sceleratus L. [From Latin rana = little frog, and sceleratus = wicked] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Celery-leaved buttercup, cursed crowfoot, shi long rui (Chinese), gae gu ri ja ri (Korean). Synonyms: Hecatonia palustris L., Hecatonia scelerata (L.) Fourr., Ranunculus holophyllus Hance, Ranunculus oryzetorum Bunge, Ranunculus sceleratus var. multifidus Nutt., Ranunculus sceleratus var. sinensis H. Lév. & Vaniot. Habitat: It is a medium-sized annual herb found in the wet spots of the northern temperate zone of both hemispheres. Diagnosis: The root of Ranunculus sceleratus L. is fibrous. The stems are fleshy, light green, branched, and grow to a height of 1 m. The petiole is 1–10 cm long. The blade is lobed, pentagonal, reniform, and 1 cm × 1.5 cm to 4 cm × 5 cm. The lateral lobes are ovate and bilobed. The inflorescence is a terminal, corymbose, and compound monochasium. The flowers are 0.5 cm in diameter. The receptacle is bullet shaped. The calyx comprises 5 sepals that are elliptical and 0.2 cm long. The corolla consists of 5 petals that are yellow, ovate, 0.5 cm × 0.2 cm, and round at the apex. The androecium consists of 10–20 anthers that are elliptical. The fruits are cylindrical and consist of innumerable tiny follicles that are green and 0.5 cm long (Figure 4.9). Medicinal uses: In China, this plant is used to treat colds, arthritis, rheumatism, fatigue, and weakness. In Cambodia, Laos, and Vietnam, this plant is used to treat indigestion, to perfume the mouth, to treat kidney diseases, and to heal abscesses. Constituents: Ranunculus sceleratus L. contains protoanemonin, anemonin, and ranunculin that are acrid and poisonous.75 The plant may contain some alkaloids such as indolopyridoquinazoline alkaloid glycosides that are found in Ranunculus ternatus Thunb.76 Pharmacology: The anti-inflammatory property of this plant has been validated using several experiments including acute inflammation induced by 12-O-tetradecanoylphorbol-13acetate, arachidonic acid, and carrageenan. This effect is perhaps conveyed by anemonin, which inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.77 Besides, an extract of leaves showed antifungal activity on probable account of protoanemonin.78−80

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FIGURE 4.9  Ranunculus sceleratus L. CH2

O

O Protoanemonin

Bioresource: In vitro pharmacological study of indolopyridoquinazoline alkaloids for their effects on cancer. The next plant discussed in this section is Semiaquilegia adoxoides (DC.) Makino. 4.1.1.10  Semiaquilegia adoxoides (DC.) Makino [From Latin semi = half, and aquilegia = eagle’s claw, and adoxoides = resembling Adoxa] History: This plant was first formally described in Regni Vegetabilis Systema Naturale by Augustin Pyramus de Candolle in 1817. de Candolle (1778–1841) was a Swiss botanist. Common names: Spurless columbine, tian kui (Chinese), gae gu ri bal top (Korean). Basionym: Isopyrum adoxoides DC. Synonyms: Aquilegia adoxoides (DC.) Ohwi, Semiaquilegia adoxoides var. grandis D.Q. Wang, Semiaquilegia dauciformis D.Q. Wang. Habitat: It is a perennial herb found in the forests of China, Korea, and Japan. It is cultivated as an ornamental plant.

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Diagnosis: The tuber of Semiaquilegia adoxoides (DC.) Makino is blackish brown and 5 cm × 0.5 cm. The stems are hairy, branched, and grow to a height of 35 cm. The petiole is 3–15 cm long. The blade is foliolate, 2.5–3 cm long, and glabrous. The leaflets are rhombic, 0.5 cm × 1 cm to 2 cm × 3 cm, and incised. The flowers are nodding and 0.5 cm in diameter. The sepals are white purple, elliptical, 0.5 cm × 0.2 cm, and acute at the apex. The petals are spatulate, 0.3 cm long, pure white, and subtruncate at the apex. The staminodes are white, linear, membranaceous, and glabrous. The anthers are yellow and conspicuous. The follicles are ovoid-elliptical, 0.6 cm long, and striate. The seeds are ovoid-elliptical and minute (Figure 4.10). Medicinal uses: In China, this plant is used to treat urogenital infection, tuberculosis, dry skin, and to remove lymph glands from the neck. Constituents: The roots of Semiaquilegia adoxoides (DC.) Makino contain griffonilide, lithospermoside, and the alkaloid magnoflorine, as well as series of ent-kaurane-type diterpenes.81,82 Pharmacology: Note that magnoflorine is cytotoxic against human epithelial cervical cancer (Hela), human hepatocellular liver carcinoma (HepG2), and human glioblastoma (U251) cells cultured in vitro.83 O H3CO

NH

O N+

HO

H

CH3 CH3

HO H3CO H3CO Magnoflorine

FIGURE 4.10  Semiaquilegia adoxoides (DC.) Makino.

OCH3 (−)-Nordicentrine

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The antitubercular activity of the plant could be attributed to magnoflorine as aporphine alkaloids are known to elicit antimycobacterial activity. One such alkaloid is nordicentrine obtained from Goniothalamus laoticus Finet & Gagnep. (order Magnoliales, family Annonaceae) that elicited antimycobacterial activity against Mycobacterium tuberculosis with a minimum inhibitory concentration of 12.5 μg/mL.84 Bioresource: In vitro pharmacological study of magnoflorine and congeners as antimycobacterial agents. Antibacterial agents are common in the next clade: the family Lardizabalaceae.

4.1.2  Family Lardizabalaceae R.Br., 1821, nom. cons., the Lardizabala Family The family Lardizabalaceae consists of 8 genera and about 30 species of woody climbers and shrubs that are notorious for accumulating tannins and triterpenoid saponins. The leaves are alternate and digitately compound. The flowers are racemose, unisexual, actinomorphic, and develop with the leaves from perulate buds. The calyx consists of 3–6 imbricate sepals. The corolla consists of 6 ­petals that are smaller than the sepals. The androecium is made of 6 stamens that are free or connate. The gynoecium consists of 3 free carpels. The fruits are succulent, colored, and consist of indehiscent ripe carpels. A classical example of Lardizabalaceae is Akebia quinata (Thunb.) Decne. (chocolate vine) that is grown as a porch vine in the United States. Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson is discussed in this section. 4.1.2.1  Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson [After Charles Sprague Sargent (1841–1927), director of the Arnold Arboretum of Harvard University, and from Latin cuneata = wedge-shaped] History: This plant was first formally described in Hooker’s Icones Plantarum by Daniel Oliver in 1889. Oliver (1830–1916) was a British botanist. Common name: Daxue teng (Chinese). Basionym: Holboellia cuneata Oliv. Synonym: Sargentodoxa simplicifolia S.Z. Qu & C.L. Min. Habitat: It is a deciduous woody climber found in the forests of China, Vietnam, and Laos. It is cultivated as an ornamental plant for gardens. Diagnosis: The bark of Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson is fissured longitudinally. The stems exude a red sap and show spectacular radiated markings in the cross section. The stems are red brown and terete. The leaves are trifoliolate and dull green. The petiole is 5–10 cm long, slender, and channeled. The leaflets are unequal in size, dark green, and glossy. The lateral leaflets are subsessile, deltoid, and asymmetrical. The petiolule of the terminal leaflet is 0.5–1 cm long. The blade is rhomboid, 5 cm × 3 cm to 15 cm × 3 cm, cuneate at the base, and acute at the apex. The inflorescence is a solitary, densely flowered, loose, globose, pendulous, and 15-cm-long raceme. The flowers are fragrant and yellowish. The male flowers comprise 5 sepals that are oblong and 1 cm × 0.5 cm. The petals are rhomboid and minute. The stamens are 0.5 cm long. The filaments are minute. The anthers are oblong. The female flower presents a receptacle which is globose and 1.5 cm × 1.2 cm. The fruits are numerous, blue, berry-like, stipitate, and 0.7–1 cm in diameter. The seeds are blackish, ovoid, and 0.5 cm long (Figure 4.11). Medicinal uses: In China, this plant is used to treat stomach ulcers, sores, rheumatism, to expel worms from the intestines, and to activate the circulation of blood. Pharmacology: Extracts of Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson abrogated the survival of Gram-positive Staphylococcus aureus, Actinomyces viscosus, and

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FIGURE 4.11  Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson. (From Coll.: W. C. Cheng. Herbarium of Biological Laboratory. The Science Society of China, Nankin, China. No. 2312. Loc.: China, Chekiang Western Tienmushan. Date: April 16, 1931.)

Gram-negative Pseudomonas aeruginosa and Coxsackie virus B3 cultured in vitro on probable account of cuneatasides A and B that elicited dramatic antibacterial activity against Gram-positive Staphylococcus aureus and Micrococcus epidermidis cultured in vitro.85−88 The plant produces triterpene saponins such as rosamultin and kajiichigoside F1.89 O

O

OH

O OH HO

HO OH Cuneataside B

Bioresource: In vitro pharmacological study of cuneataside for its effect on acne. Triterpenoids are common in the next clade: the superorder Rosanae, discussed in Chapter 5.

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77. Lee TH, Huang NK, Lai TC, Yang AT, Wang GJ, 2008, Anemonin, from Clematis crassifolia, potent and selective inducible nitric oxide synthase inhibitor. J Ethnopharmacol; 116(3):518–527. 78. Misra SB, Dixit SN, 1978, Antifungal properties of leaf extract of Ranunculus sceleratus L. Experientia; 34(11):1442–1443. 79. Martín ML, San Román L, Domínguez A, 1990, In vitro activity of protoanemonin, an antifungal agent. Planta Med; 56(1):66–69. 80. Tocan V, Baron O, 1969, Antibiotic effect of protoanemonin isolated from Ranunculus oxyspermus M.B. Boll Chim Farm; 108(12):789–791. 81. Han QB, Jiang B, Mei SX, Ding G, Sun HD, Xie JX, Liu YZ, 2001, Constituents from the roots of Semiaquilegia adoxoides. Fitoterapia; 72(1):86–88. 82. Niu F, Chang HT, Jiang Y, Cui Z, Chen FK, Yuan JZ, Tu PF, 2006, New diterpenes from Semiaquilegia adoxoides. J Asian Nat Prod Res; 8(1–2):87–91. 83. Mohamed SM, Hassan EM, Ibrahim NA, 2009, Cytotoxic and antiviral activities of aporphine alkaloids of Magnolia grandiflora L. Nat Prod Res; 16:1–8. 84. Lekphrom R, Kanokmedhakul S, Kanokmedhakul K, 2009, Bioactive styryllactones and alkaloid from flowers of Goniothalamus laoticus. J Ethnopharmacol; 125(1):47–50. 85. Xiao Y, Liu T, Huang Z, Zhou X, Li G, 2002, The in vitro study of the effects of 11 kinds of traditional Chinese medicine on the growth and acid production of Actinomyces viscosus. Hua Xi Yi Ke Da Xue Xue Bao; 33(2):253–255. 86. Li J, Jin Z, Shao H, 2005, The antimicrobial activity of the extract ion from leaves of Sargentodoxa cuneata, Zhong Yao Cai; 28(10):906–909. 87. Guo JP, Pang J, Wang XW, Shen ZQ, Jin M, Li JW, 2006, In vitro screening of traditionally used medicinal plants in China against enteroviruses. World J Gastroenterol; 12(25):4078–4081. 88. Chang J, Case R, 2005, Phenolic glycosides and ionone glycoside from the stem of Sargentodoxa cuneata. Phytochem; 66(23):2752–2758. 89. Rücker G, Mayer R, Shin-Kim JS, 1991, Triterpene saponins from the Chinese drug “Da Xueteng” (Caulis sargentodoxae). Planta Med; 57(5):468–470.

5

Superorder Rosanae Takht., 1967*

5.1  EUROSIDS I Eurosids I (Fabids or Fabidae) include a compelling array of triterpenoids and phenolics (flavonoids, quinones, tannins) that await pharmacological testing for their effects on cancer, bacterial, fungal, viral and parasitic infection, as well as inflammation and skin ageing. Cytotoxic: The triterpene quinone scutione isolated from the root bark of Maytenus scutioides (Griseb.) Lourteig & O’Donell (order Celastrales, family Celastraceae) exhibited cytotoxic properties against human epithelial cervical cancer (Hela), human laryngeal carcinoma (Hep2), and African green monkey kidney (Vero) cells with IC50 values of 4.9, 5.6, and 7.2 μg/mL, respectively.1 A xanthone isolated from Polygala vulgaris L. (order Fabales, family Polygalaceae) displayed some levels of toxicity against human colorectal carcinoma (Lovo) cells lines with an IC50 value of 8.3 M.2 The naphthoquinone mansonone E isolated from the root bark of Ulmus pumila L. (order Rosales, family Ulmaceae) impaired the proliferation of human malignant melanoma (A375-S2), human epithelial cervical cancer (Hela), human breast adenocarcinoma (MCF-7), and human histiocytic lymphoma (U937) cells with IC50 values of 2.2, 7.9, 3.1, and 0.9 M, respectively.3 Cucurbitacin B, a triterpenoid, isolated from the rhizomes of Begonia nantoens M.J. Lai  & N.J. Chung (order Cucurbitales, family Begoniaceae) impeded the survival of human stomach cancer (NUGC-3) cells with an IC50 value of 0.2 g/mL.4 A biflavonoid isolated from the leaves of Luxemburgia nobilis Eichler (order Malpighiales, family Ochnaceae) abated the growth of murine Ehrlich carcinoma and human erythromyeloblastoid leukemia (K562) cells with IC50 values of 17.2 M and 89 μM, respectively, via inhibition of the enzymatic activity of topoisomerase I and II.5 A lignan isolated from Larrea tridentata (Sessé & Moc. ex DC.) Coville (order Zygophyllales, family Zygophyllaceae) inhibited the growth of human melanoma (ACC375), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (SW480) cells with IC50 values of 7 5 μM, 3 M, and 55 M, respectively.6 Isorhamnetin isolated from Hippophae rhamnoides L. (order Rosales, family Elaeagnaceae) compromised the survival of human hepatocellular carcinoma (BEL-7402) cells with an IC50 value equal to 74.4 g/mL.7 The diterpenes cassipourol and cassipourin acetate isolated from Cassipourea madagascariensis DC. (order Malpighiales, order Rhizophoraceae) inhibited the growth of human ovarian cancer (A2780) cells with IC50 values of 2.4 and 2.8 μg/mL, respectively.8 The flavonoids kaempferol and maesopsin isolated from the bark of Berchemia floribunda (Wall.) Brongn. (order Rosales, family Rhamnaceae) showed cytocidal effects against human leukemic lymphoblast (CCRF-CEM) cells.9 A diarylheptanoid isolated from the bark of Betula papyrifera Marshall (order Fagales, family Betulaceae) was cytotoxic against human lung adenocarcinoma epithelial (A549), human colon carcinoma DLD-1, and human normal skin fibroblast (WS1) cells with IC50 values of 30 μM, 20.8 M, and  20.6 μM, respectively.10 The anthracene derivative scutianthraquinone B isolated *

The superorder Rosanae comprises two major groups of flowering plants: Eurosids I and Eurosids II.

215

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Medicinal Plants of China, Korea, and Japan

from the bark of Scutia myrtina (Burm. f.) Kurz (order Rosales, family Rhamnaceae) was toxic for human ovarian cancer (A2780) cells and Plasmodium falciparum with IC50 values of 5.8 and 1.1 μM, respectively.11 The diterpenes trigoxyphins A and B isolated from the stems of Trigonostemon xyphophylloides (Croizat) L.K. Dai & T.L. Wu (order Malpighiales, family Euphorbiaceae) were strongly cytotoxic against human promyelocytic leukemia (HL-60) cells with IC50 values of 0.2 and 0.5 μM, respectively, and against human lung adenocarcinoma epithelial (A549) tumor cells with IC50 values of 7.5 and 4.9 μM, respectively.12 The polyphenol albanol A isolated from the bark of Morus alba L. (order Rosales, family Moraceae) was cytotoxic against human promyelocytic leukemia (HL-60) and human melanoma (CRL1579) cells with IC50 values of 1.7 and 9.8 μM, respectively.13 Antibacterial and antifungal: The triterpene quinone scutione isolated from the root bark of Maytenus scutioides (Griseb.) Lourteig & O’Donell (order Celastrales, family Celastraceae) inhibited the growth of a broad array of bacteria, including Gram-positive Bacillus cereus with a minimum inhibitory concentration of 0.1 μg/mL.1 The biflavonoid sulcatone A isolated from the leaves of Ouratea sulcata Van Tiegh (ex Keay) (order Malpighiales, family Ochnaceae) exhibited antibacterial activity against Gram-positive Staphylococcus aureus and Bacillus subtilis with minimum inhibitory concentrations of 12.5 and 8.1 μg/mL, respectively.14 The xanthone toxyloxanthone C isolated from the roots of Cudrania fruticosa (Roxb.) Wight ex Kurz (order Rosales, family Moraceae) displayed some level of antifungal activity against Candida albicans with a minimum inhibitory concentration of 25 μg/mL.15 The anthracene derivative peroxisomicine A1 isolated from the fruits of Karwinskia parvifolia Rose (order Rosales, family Rhamnaceae) abrogated the survival of Candida albicans with an IC50 value of 8 μg/mL.16 The sesquiterpene orbiculin G isolated from the roots of Microtropis fokienensis Dunn (order Celastrales, family Celastraceae) inhibited the growth of Mycobacterium sp. cultured in vitro with a minimum inhibitory concentration of 14.6 μM.17 The prenylated phenol cannabigerol isolated from Cannabis sativa L. (order Rosales, family Cannabaceae) exhibited profound antibacterial properties against several strains of Gram-positive Staphylococcus aureus with minimum inhibitory concentrations of 1–2 μg/mL.18 The flavonoid derivative piliostigmol isolated from the leaves of Piliostigma reticulatum (DC.) Hochst. (order Fabales, family Fabaceae) exhibited dramatic antibacterial effects against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli with minimum inhibitory concentrations of 3.2 and 2.5 μg/mL, respectively.19 The flavonoid derivative moracin T isolated from the bark of Morus mesozygia Stapf (order Rosales, family Moraceae) mitigated the proliferation of Gram-positive Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis, and Gram-negative Escherichia coli, Shigella dysenteriae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, and the fungi Candida albicans and Microsporum audouinii with minimum inhibitory concentrations less than 40 μg/mL.20 Parasiticidal: The phenolic 4-hydroxy-1-tetralone isolated from Ampelocera edentula Kuhlm. (order Rosales, family Ulmaceae) protected rodents at a dose of 50 mg/kg against Leishmania amazonensis infestation.21 The phenolic glycoside bergenin extracted from the leaves of Flueggea virosa (Roxb. ex Willd.) Royle (order Malpighiales, family Phyllanthaceae) inhibited the growth of Trypanosoma brucei with an IC50 value of 1 μM.22 The triterpene quinone isoiguesterol extracted from the root of Salacia kraussii (Harv.) Harv. (order Celastrales, family Celastraceae) abrogated the survival of Plasmodium falciparum with an IC50 value of 22.9 ng/mL.23 The triterpene quinones isoiguesterin and 20-epi-isoiguesterinol extracted from the roots of Salacia madagascariensis (Lam.) DC. (order Celastrales, family Celastraceae) elicited profound ­a ntiprotozoal activity against Leishmania donovanii with IC50 values of 0.03 and

Superorder Rosanae Takht., 1967

217

0.02 μg/mL, respectively.24 A triterpenoid isolated from the fruits of Bruguiera parviflora Wight (order Malpighiales, family Rhizophoraceae) displayed significant parasiticidal activity against Plasmodium falciparum with an EC50 value of 8.6 μg/mL.25 The phenolic glycoside rourinoside isolated from Rourea minor (Gaertn.) Alston (order Oxalidales, family Connaraceae) elicited an antiplasmodial property against Plasmodium falciparum with an IC50 value of 3.6 μg/mL.26 A biflavanone isolated from the bark of Ochna integerrima Merr. (order Malpighiales, family Ochnaceae) elicited a dramatic parasiticidal activity against Plasmodium sp. with an IC50 value of 80 ng/mL.27 The triterpene oleanolic acid isolated from Viola verecunda A. Grey. (order Malpighiales, family Violaceae) was antiplasmodial with an IC50 value of 0.1 μg/mL against Plasmodium falciparum.28 A triterpene isolated from Lophanthera lactescens Ducke (order Malpighiales, family Malpighiaceae) abrogated the survival of Leishmania amazonensis cultured in mouse peritoneal macrophages with an IC50 value 0.4 μg/mL.29 The flavonoid phaseollidin isolated from the bark of Erythrina fusca Lour. (order Fabales, family Fabaceae) exhibited an antiplasmodial property against Plasmodium falciparum with an IC50 value of 9 μg/mL.30 The xanthone mangostanin isolated from the stem bark of Pentadesma butyracea Sabine (order Malpighiales, family Clusiaceae) abated the survival of Plasmodium falciparum with an IC50 value of 3.9 μg/mL.31 The biflavonoid derivative 5,5″-di-O-methyldiphysin extracted from the roots of Ormocarpum kirkii S. Moore (order Fabales, family Fabaceae) abrogated the survival of Trypanosoma cruzi, Leishmania infantum, Trypanosoma brucei, and Plasmodium falciparum with IC50 values of 20.4, 32.5, 17.6, and 21.1 μM, respectively.32 Antiviral: Xanthohumol iolated from Humulus lupulus L. (order Rosales, family Cannabaceae) inhibited by 54.2% of the production of p24 antigen in the human immunodeficiency virus chronically infected H9 cells at a dosage of 50 μg/mL.33 Indole-3-carboxylic acid isolated from the rhizomes of Begonia nantoens M.J. Lai & N.J. Chung (order Cucurbitales, family Begoniaceae) inhibited the replication of the human immunodeficiency virus cultured in H9 lymphocytic cells with an EC50 value of 2.4 μg/mL.4 The flavonoids ochnaflavone 7″-O-methyl ether and 2″,3″-dihydroochnaflavone 7″-O-methyl ether from the aerial parts of Ochna integerrima (Lour.) Merr. (order Malpighiales, family Ochnaceae) inhibited the replication of the human immunodeficiency virus in vitro with EC50 values of 2 and 0.9 μg/mL, respectively, via the inhibition of the enzymatic activity of reverse transcriptase.34 The stilbene oxyresveratrol isolated from the heartwood of Artocarpus lakoocha Wall. ex Roxb. (order Rosales, family Moraceae) inhibited the replication of the herpes simplex virus type 1, herpes simplex virus type 2, poliovirus, and measles virus with IC50 values of 24, 18.7, 65, and 90 μg/mL.35 The flavonoids 3-deoxysappanchalcone and sappanchalcone isolated from the wood of Caesalpinia sappan L. (order Fabales, family Fabaceae) abrogated the replication of the influenza virus with IC50 values of 1 and 2 μg/mL, respectively.36 The indole alkaloid trigonoliimine A extracted from the leaves of Trigonostemon lii Y.T. Chang (order Malpighiales, family Euphorbiaceae) inhibited the replication of the human immunodeficiency virus with an EC50 value of 0.9 μg/mL.37 A xanthone extracted from the root bark of Garcinia edulis Exell (order Malpighiales, family Clusiaceae) inhibited the enzymatic activity of the human immunodeficiency virus protease with an IC50 value of 11.3 μg/mL.38 The diarylheptanoid platyphyllone isolated from the bark of Alnus japonica (Thunb.) Steud. (order Fagales, family Betulaceae) was antiviral against the influenza virus with an EC50 value of 29.9 μM.39 Anti-inflammatory: The flavonoid tricin extracted from the leaves of Agelaea pentagyna (Lam.) Baill. (order Oxalidales, family Connaraceae) inhibited the exocytosis of granules from rat leukemia basophils exposed to antigens with an IC50 value of 4.3 μM.40 The

218

Medicinal Plants of China, Korea, and Japan

d­ iarylheptanoid 12-hydroxymyricanone isolated from the roots of Myrica nana A. Chev. (order Fagales, family Myricaceae) inhibited the secretion of nitric oxide by macrophages exposed to lipopolysaccharides with an IC50 value of 30.1 μM.41 Central nervous system: The indolizidine alkaloid grandisine A isolated from Elaeocarpus grandis F. Muell. (Order Oxalidales, family Elaeocarpaceae) inhibited the binding of iodinated deltorphin to the human delta-opioid receptor at 2.7 μM.42 Cosmetology: A triterpene isolated from the oil of Oenothera biennis L. (order Myrtales, family Onagraceae) inhibited the enzymatic activity of elastase with an IC50 value of 0.2 μg/mL.43 The triterpene canophyllol that is present in Calophyllum inophyllum L. (order Malpighiales, family Calophyllaceae) inhibited the enzymatic activity of elastase with an IC50 value of 2.5 μM.44,45 The phenolic 5-caffeoylquinic acid isolated from Euonymus alatus Regel (order Celastrales, family Celastraceae) inhibited the enzymatic activity of matrix-metalloproteinase with an IC50 value of 30 nM.46 The flavonoids phloretin and 3-hydroxyphloretin isolated from the leaves of Malus doumeri A. Chev. var. formosana (Kawak. & Koidz. ex Hayata) S.S. Ying (order Rosales, family Rosaceae) inhibited the enzymatic activity of elastase by 51.8% and 32.3% at doses of 36.5 and 34.5 μM, respectively.47 The phenolics eicosanyl caffeate and docosyl caffeate isolated from Glycyrrhiza glabra L. (order Fabales, family Fabaceae) inhibited the enzymatic activity of elastase with IC50 values of 0.9 and 1.4 μg/ mL.48 The phenolic humulone and xanthohumol isolated from Humulus lupulus L. (order Rosales, family Cannabaceae) inhibited the enzymatic activity of metalloproteinase by 11% and 65% at a dose of 30 μg/mL.49 Xanthohumol isolated from Humulus lupulus L. significantly inhibited the enzymatic activity of elastase.50 The phenolics catechin, epicatechin, procyanidin B-1, and procyanidin B-3 isolated from Ficus microcarpa L.f. (order Rosales, family Moraceae) inhibited the enzymatic activity of hyaluronidase.51 The flavonoid 3-prenyl luteolin isolated from the wood of Artocarpus heterophyllus Lam. (order Rosales, family Moraceae) inhibited the enzymatic activity of tyrosinase with an IC50 value of 76.3 μM.52 Eurosids I include the orders Fabales, Cucurbitales, Rosales, Oxalidales, Malpighiales, Zygophyllales, Fagales, and Celastrales.

5.1.1  Order Celastrales Link, 1829 The order Celastrales consists of two families of flowering plants: the Celastraceae and the Lepidobotryaceae. 5.1.1.1  F amily Celastraceae R.Br. in M. Flinders, 1814, nom. cons., the Bittersweet Family The family Celastraceae consists of about 50 genera and 800 species of trees, shrubs, or climbers, principally tropical and notorious for accumulating triterpene quinones of pharmacological interest. The leaves of Celastraceae are simple, often glossy and serrate, and alternate or opposite. The inflorescence is a terminal or axillary cyme. The flowers are hermaphrodite, small, actinomorphic, greenish or white, hypogynous, and succulent. The perianth comprises 5 sepals and 5 petals that are small and imbricate. The androecium consists of 5 stamens that are alternate with the petals. The receptacle displays a conspicuous nectary disc. The anthers are tetrasporangiate and dithecal. The gynoecium consists of 2–5 carpels forming a superior ovary with 2–5 locules. The styles are terminal, short, and capitates, and develop a stigma with 2–5 lobes. The fruits are capsules, samaras, berries, or drupes.

219

Superorder Rosanae Takht., 1967 H3C

H3C Cl

O

H3C

HO

O N

CH3

O

O O

N

CH3 H3C O N OH H OCH3

CH3

O

Maytansine

O H3C

O

CH3

O

CH3

CH3 O

OH

H3C

H

O

CH3

CH3

O

HO OH

O

  

OCH3

Triptolide



Pristimerin

The dried leaves of Catha edulis Forsk. (khat) are used in a number of African and Arab countries to invigorate the intellect and to assuage hunger. The active agent of khat is an epinephrine-like phenethylamine alkaloid known as (−)-cathinone. Another notorious example of Celastraceae is the ornamental Euonymus europaeus L. (spindle tree), the fruits of which are poisonous. Euonymus (British Pharmaceutical Codex, 1954) consists of the dried root bark of Euonymus atropurpureus Jacq. and has been used as a tincture (0.6–2.6 mL) as a mild purgative and choleretic. To date, pharmacological studies on Celastraceae have provided compelling results and the discovery of natural products of pharmacological interest is very probable in this family. A number of plants classified within the genus Maytenus Molina contain macrocyclic alkaloids of possible bacterial origin, such as maytansine, that are able to inhibit the proliferation of tumors at very low dosage.53 The diterpenes triptolide and tripdiolide isolated from Tripterygium wilfordii Hook.f. displayed dramatic antileukemic properties.54 Another interesting feature of Celastraceae is the production of unusual series of quinonemethide triterpenes. One such compound is pristimerin that is antibacterial, antifungal, antiviral, and cytotoxic via caspase apoptosis induction.55−58 The first plant discussed in this section is Hippocratea indica Willd.

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Medicinal Plants of China, Korea, and Japan

5.1.1.1.1  Hippocratea indica Willd. [After Hippocrates (480–377 BC), father of medicine, pharmaceutical botanist, and founder of Hippocratic Oath, and from Latin indica = from India] History: This plant was first formally described in Species Plantarum. Editio Quarta by Carl Ludwig Willdenow in 1797. Willdenow (1765–1812) was a German botanist. Common name: Sand paddle-pod. Synonyms: Hippocratea loesneriana Hutch. & M.B. Moss, Pristimera indica (Willd.) A.C. Sm., Reissantia indica (Willd.) N. Hallé. Habitat: It is a large climber found in the forests of India, Malaysia, and Indonesia. Diagnosis: The leaves of Hippocratea indica Willd. are simple, opposite, membranaceous, elliptical, acuminate, crenulate, and blunt at the base and apex. The petiole is 5 cm long. The blade has 6 pairs of secondary nerves and is 6.5 cm × 3 cm to 9 cm × 4.5 cm. The panicle is 10 cm wide. The flowers are innumerable, white, and 1.5 cm wide. The calyx lobes are triangular and hairy. The petals are oblong. The fruits consist of a pair of carpels that are oblong, blunt, striate, and 6 cm long. Each carpel encloses a pair of seeds (Figure 5.1). Medicinal uses: In Malaysia, this plant is given postpartum and is used to promote menses, to treat fatigue, and to remove ringworm. In Indonesia, this plant is used to break fever and to treat rheumatism, and it is given at parturition. Pharmacology: The anti-inflammatory property of Hippocratea indica Willd. is validated: an extract of the plant displayed anti-inflammatory activity in the carrageenan-induced paw edema experiment. Besides, the extract exhibited a significant antibacterial activity against Gram-positive Staphylococcus aureus with a minimum inhibitory concentration of 16 μg/ mL.59 The active constituent involved here is apparently unknown but some triterpenes could be involved as alpha- and beta-amyrin, oleanolic and ursolic acids were reported from Hippocratea excelsa Kunth.60

FIGURE 5.1  Hippocratea indica Willd.

Superorder Rosanae Takht., 1967

221

Note that ursolic and oleanolic acids isolated from Miconia species (order Myrtales, family Melastomataceae) displayed a significant antibacterial effect against Gram-positive Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis achieving minimum inhibitory concentrations of 30–80 μg/ mL.61 Besides, ursolic acid isolated from Curtisia dentata (Burm. f.) C.A. Smith (order Cornales, family Cornaceae) showed dramatic antifungal activities.62 Bioresource: In vitro pharmacological study of ursolic acid for its effect on acne. The next plant discussed in this section is Salacia flavescens Kurz. 5.1.1.1.2  Salacia flavescens Kurz [From Latin Salacia = Neptune’s wife, and flavescens = becoming yellow] History: This plant was first formally described in Journal of the Asiatic Society of Bengal by Wilhelm Sulpiz Kurz in 1872. Kurz (1834–1878) was a German botanist. Common names: Katimbong, sedang (Malay). Synonyms: Salacia ovalis Lawson, Salacia lawsoni King. Habitat: It is a sarmentose shrub found in the rainforests of Malaysia. Diagnosis: The petiole of Salacia flavescens Kurz is stout and 0.5 cm long. The leaves are simple, opposite, coriaceous, oblong, round at the base, acuminate at the apex, 10 cm × 2.5 cm to 20 cm × 5 cm, and have 5–9 pairs of secondary nerves. The inflorescence is an axillary cluster. The flowers are orangish and 0.5 cm wide. The calyx lobes are ovate and acute. The petals are twice as long as the petals and elliptical. The androecium includes 3 stamens. The filaments are triangular. The fruits are globular, 5 cm in diameter, orange, and enclose a sweet white pulp and a few seeds (Figure 5.2). Medicinal use: In Malaysia, the roots are boiled in water and the liquid obtained is drunk postpartum. Pharmacology: Apparently unknown. The plant probably contains some antibacterial and antioxidant quinonemethide triterpenes such as pristimerin, maytenin, 20-alpha-hydroxymaytenin, netzahualcoyene, and salacin, which have been found in Salacia campestris

FIGURE 5.2  Salacia flavescens Kurz.

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Cambess. ex Walp.63 Besides, one could reasonably expect to find some astringent proanthocyanidins in Salacia flavescens Kurz as such compounds have been found in Salacia chinensis L., hence the postpartum use of the plant.64 Bioresource: Phytochemical and pharmacological investigations and anticancer quinonemethide triterpene(s). The next plant discussed in this section is Salacia grandiflora Kurz. 5.1.1.1.3  Salacia grandiflora Kurz [From Latin Salacia = Neptune’s wife, and grandiflora = with large flowers] History: This plant was first formally described in Journal of the Asiatic Society of Bengal by Wilhelm Sulpiz Kurz in 1872. Kurz (1834–1878) was a German botanist. Common names: Nasi sejuk, ampedal ayam (Malay). Synonym: Salacia longifolia Lawson. Habitat: It is a large climbing shrub found in the rainforests of Burma and Malaysia. Diagnosis: The petiole of Salacia grandiflora Kurz is 1.5 cm long. The leaves are simple, opposite, coriaceous, and broadly elliptical. The blade is 15 cm × 5 cm to 20 cm × 10 cm and has 7–10 pairs of secondary nerves. The flowers are glabrous, white, 0.75 cm long, and are arranged in groups of 3 or more on short axillary tubercles. The calyx is cupular. The calyx lobes and the petals are orbicular. The androecium consists of 3 stamens. The fruits are globular, 3.5 cm in diameter, and orange. The seeds are embedded in a sweet pulp (Figure 5.3). Medicinal use: In Malaysia, this plant is used to induce menses. Pharmacology: Apparently unknown. One could propose that the emmenaguoge property of the plant involves some quinonemethide triterpenes that somewhat share some structural similarities with estradiol. Bioresource: In vitro pharmacological study of pristimerin and its derivatives for their effect on breast cancer. Another estrogenic plant is Salacia prinoides (Willd.) DC., discussed next.

FIGURE 5.3  Salacia grandiflora Kurz. (From Coll.: L. Wray. Det.: Ding Hou. Flora Malesiana. Herbarium Museum of Perak. No. 750. Loc.: Malaysia, Changkat Serdang. Date: August 1963.)

223

Superorder Rosanae Takht., 1967 O

OCH3

H3C CH3 OH

CH3 H 3C

H

O

CH3

CH3 HO

HO OH

Estradiol

Pristimerin

5.1.1.1.4  Salacia prinoides (Willd.) DC. [From Latin Salacia = Neptune’s wife, and prinoides = resembles Prinos—an evergreen oak] History: This plant was first formally described in Der Gesellsschaft Naturforschender Freunde zu Berlin, neue Schriften by Carl Ludwig Willdenow in 1803. Willdenow (1765– 1812) was a German botanist. Basionym: Tontelea prinoides Willd. Habitat: It is a climbing shrub found in the rainforests of Malaysia, Indonesia, China, and the Philippines. Diagnosis: The petiole of Salacia prinoides (Willd.) DC. is 0.6 cm long. The leaves are simple, opposite, and coriaceous. The blade is elliptical, crenulate, cuneate at the base, round at the apex, 5 cm × 3 cm to 10 cm × 5 cm, and has 5 or 6 pairs of secondary nerves. The flowers are 0.7 cm wide, brown, and grouped on small axillary tubercles. The calyx lobes are round. The petals are cordate, obtuse, and clawed at the base. The androecium includes 3 stamens. The fruits are globular, red, 1.5 cm in diameter, edible, and enclose a single seed (Figure 5.4).

FIGURE 5.4  Salacia prinoides (Willd.) DC. (From Coll.: S.K. Lau. Det.: D. Merrill. Flora of Hainan. Loc.: China, Ngai district. Date: June 25, 1932.)

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Medicinal Plants of China, Korea, and Japan

Medicinal uses: In the Philippines, the roots are boiled in water and the liquid obtained is used to induce and regulate menses and for abortions. In India, this plant is used to treat diabetes. Constituents: Salacia prinoides (Willd.) DC. contains lupeol, ursolic acid, beta-sitosterol, daucosterol, flavonoids—quercetin, quercetin-3′,4′-dimethylether, isorhamnetin, and kaempferol-4′-methylether, and phenolic acids—gallic acid and ethyl gallate.65 Pharmacology: The plant produces the thiosugar sulfonium sulfate salaprinol that may have alpha-glucosidase inhibitory activity, hence the antidiabetic use mentioned above.66 Besides, the emmenaguoge property might be owed to some estrogenic substances that are yet to be identified. One might be curious to look for estrogenic quinonemethide triterpenes in Salacia prinoides (Willd.) DC.

OH

OSO3–

S HO

HO

OH

Salaprinol

Bioresource: In vitro pharmacological study of salaprinol and its derivatives for their effect on diabetes. Triterpenoids occur in the next clade: the order Fagales.

5.1.2  Order Fagales Engl., 1892 The order Fagales comprises seven families of flowering plants of which the Myricaceae is ­discussed here. 5.1.2.1  Family Myricaceae Rich. ex Kunth, 1817, nom. cons., the Bayberry Family The family Myricaceae consists of 9 genera and about 50 species of shrubs or treelets accumulating triterpenes, sesquiterpenes, and proanthocyanidins. The leaves are alternate, simple, and without stipules. The inflorescence is a compact ament. The perianth is inexistent. The androecium consists of 6 stamens. The anthers are tetrasporangiate, dithecal, extrorse, and open by longitudinal slits. The gynoecium consists of a pair of carpels that are united to form a compound unilocular ovary. The styles are distinct. The ovule is solitary, basal, and erect. The fruits are drupaceous. Bayberry (British Pharmaceutical Codex, 1949) consists of the dried bark of the roots of Myrica cerifera L. that contain tannic and gallic acids. Bayberry is astringent and emetic at high doses. It has been administered in the form of an infusion. The powdered bark mixed with ginger, capsicum, and cloves was used under the name of “composition powder” as a domestic remedy for colds

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and chills. The family is yet to be explored for pharmacology. Myrica rubra (Lour.) Siebold & Zucc. is described next. 5.1.2.1.1  Myrica rubra (Lour.) Siebold & Zucc. [From Greek myrike = tamarisk, and Latin rubra = red] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Yang mei (Chinese), yamamomo (Japanese), so gwi na mu (Korean). Basionym: Morella rubra Lour. Synonyms: Daphne argyi H. Lév., Morella rubra Lour., Myrica rubra var. acuminata Nakai. Habitat: This dioecious tree grows in the forests of China, Taiwan, Japan, Korea, and the Philippines. It is also cultivated as an ornamental plant and as a fruit tree. Diagnosis: Myrica rubra (Lour.) Siebold & Zucc. grows to a height of 15 m. The bark is gray. The petiole is 0.6 cm long. The blade is obovate, 5 cm × 1 cm to 15 cm × 5 cm, leathery, cuneate at the base, and acute or round at the apex. The male spikes are 2 cm long. The male flowers have 2–4 ovate bracteoles that are ciliate. The androecium includes 4–6 stamens. The anthers are dark red and elliptical. The female spikes are solitary in leaf axils, 1 cm long, and densely flowered. The female flowers have 4 bracteoles. The ovary is velutinous. The stigmas, arranged in pairs, are bright red and slender. The drupe is crimson, palatable, spiny, globose, and 1.5 cm in diameter (Figure 5.5). Medicinal uses: In China, this plant is used to excite the discharge of urine, to expel worms from the intestines, and to treat lung disease, stomachache, vomiting, diarrhea, dysentery, poisoning, ulcers, wounds, heart disease, and cholera.

FIGURE 5.5  Myrica rubra (Lour.) Siebold & Zucc. (From Coll.: Y. Tsiang and Det.: D. Merrill. Herbarium of the College of Agriculture. Sun Yatsen University, Canton. No. 320. Loc.: China, Hong Kong, new territory. Date: April 3, 1928.)

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Pharmacology: The fruits of Myrica rubra (Lour.) Siebold & Zucc. are hepatoprotective: an extract of fruits protected rodents against CCl4-induced hepatocellular damage.67 This plant contains the flavonoid myricetin that showed remarkable analgesic effects in the acetic acid-induced abdominal writhing experiment and the formalin experiment.68 In addition, myricetin inhibited the enzymatic activity of topoisomerases I and II in human erythromyeloblastoid leukemia (K562) cells.69 Topoisomerase inhibitors have a parasiticidal property and the anthelminthic property of the plant could result from topoisomerase inhibition via myricetin.70 An extract of leaves of Myrica rubra (Lour.) Siebold & Zucc. abrogated the survival of the influenza virus cultured in vitro on probable account of prodelphinidin B-2 3,3′-di-O-gallate that induced apoptosis of human breast adenocarcinoma (MCF-7) cells and exhibited antiviral and antioxidant properties.71,72 Note that proanthocyanidins, which are astringent, and myricetin may confer to the plant properties that enable it to treat diarrhea and dysentery, and to heal wounds.73 In fact, the flavonoid myricitrin isolated from the leaves of the plant generated tumor necrosis factor-alpha by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.74

OH OH HO

O

OH

OH

H O

OH

OH

O OH

OH OH

HO

O

OH

OH

H OH

O OH

O OH

Prodelphinidin B-2 3,3′-di-O-gallate

OH OH HO

O

OH OH

OH

O Myricetin

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Bioresource: In vitro pharmacological study of myricetin for its effect on cancer. Flavonoids are common in the next clade: Eurosids II.

5.2  EUROSIDS II Eurosids II (Malvids or Malvidae) and Eurosids I have both inherited from a common ancestry the ability to augment an interesting array of phenolic substances (tannins, flavonoids, quinones) and triterpenes that are of pharmacological value in the fields of oncology, microbiology, parasitology, neurology, and cosmetology. Cytotoxic: The tannins 1-O-galloyl castalagin and casuarinin isolated from the leaves of Eugenia jambos L. (order Myrtales, family Myrtaceae) exhibited cytotoxic activities against human promyelocytic leukemia (HL-60) cells with IC50 values of 10.8  and 12.5 μM, respectively, via apoptosis induction.75 The triterpene (3Z)-coumaroylhederagenin isolated from Ludwigia octovalvis (Jacq.) P.H. Raven (order Myrtales, family Onagraceae) exhibited cytotoxic activities against human nasopharyngeal carcinoma (KB) and human colon cancer (HT-29) cells with IC50 values of 1.2 and 2.1 μM, respectively.76 A lignan isolated from the roots of Bursera tonkinensis Guillaum. (order Sapindales, family Burseraceae) was remarkably cytotoxic against human nasopharyngeal carcinoma (KB), human prostate adenocarcinoma (LNCaP), and human colon carcinoma (Col-2) cells with IC50 values of 17.7, 10, and 23.1 ng/mL.77 Flavonoid derivatives extracted from the leaves of Muntingia calabura L. (order Malvales, family Muntingiaceae) displayed cytotoxic activities against mouse leukemia (P388) and human colon cancer (HT-29) cells with IC50 values lower than 4 μg/mL.78 The terpenoid gedunin isolated from Xylocarpus granatum J. König (order Sapindales, family Meliaceae) was found to be abrogate the survival of human colon cancer (CaCo-2) cells with an IC50 value of 16.8 μM.79 The flavonoid pachypodol isolated from the leaves of Calycopteris floribunda (Roxb.) Poir. (order Myrtales, family Combretaceae) inhibited the growth of human colon cancer (CaCo-2) cells with an IC50 value of 185.6 μM.80 The phenolic mansonone E extracted from the wood of Thespesia populnea (L.) Sol. ex Corrêa (order Malvales, family Malvaceae) was strongly cytotoxic against human breast adenocarcinoma (MCF-7), human epithelial cervical cancer (Hela), human colon cancer (HT-29), and human nasopharyngeal carcinoma (KB) cells with IC50 values of 0.05, 0.5, 0.1, and 0.4 μg/mL, respectively.81 A triterpene isolated from the root bark of Helicteres angustifolia L. (order Malvales, family Malvaceae) was cytotoxic against human colorectal cancer (COLO 205), human hepatocellular liver carcinoma (HepG2), and human gastric cancer (AGS) cells with IC50 values of 22.4, 87.6, and 5.4 μM, respectively.82 The stilbenoids diptoindonesin F, (−)-ampelopsin A, ampelopsin E, and (−)-hemsleyanol D isolated from the bark of Shorea sp. (order Malvales, family Dipterocarpaceae) exhibited IC50 values of 34.6, 17, 15.3, and 94.7 μM, respectively.83 An alkylphenol isolated from the kernel of Semecarpus anacardium L. f. (order Sapindales, family Anacardiaceae) was highly cytotoxic to both drug-sensitive premalignant breast epithelial (MCF-10A) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 0.8 and 0.6 μg/mL, respectively.84 An acridone alkaloid isolated from the roots and fruits of Zanthoxylum leprieurii Guill. et Perr. (order Sapindales, family Rutaceae) exhibited cytotoxic activities against human lung adenocarcinoma epithelial (A549), human colon carcinoma (DLD1), and human normal skin fibroblast (WS1) cells with IC50 values of 31, 27, and 51 μM, respectively.85 The triterpene eurycomalactone isolated from Eurycoma longifolia Jack (order Sapindales, family Simaroubaceae) displayed dramatic cytotoxic activities against murine colon carcinoma (colon 26-L5), murine melanoma (B16-BL6), Lewis lung carcinoma (LLC), and human lung adenocarcinoma epithelial (A549) cells with IC50 values

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of 0.7, 0.6, 0.7, and 0.7 μM, respectively.86 The daphnane diterpene yuanhuadine isolated from the flowers of Daphne genkwa Siebold & Zucc. (order Malvales, family Thymelaceae) was dramatically cytotoxic against human lung adenocarcinoma epithelial (A549) and human aborted fetal (MRC-5) cells with IC50 values of 0.01 and 11.1 nM, respectively.87 Antibacterial/antifungal: The naphthalene quinone guieranone A isolated from the leaves of Guiera senegalensis J.F. Gmel. (order Myrtales, family Combretaceae) showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum at a dose of 1 μg.88 The triterpene 2-acetoxyseneganolide A isolated from the fruits of Khaya senegalensis (Desr.) A. Juss. (order Sapindales, family Meliaceae) at concentrations of 1000 and 1500 ppm showed an inhibition of mycelial growth of 61.5% and 68.3%, respectively, against the phytopathogenic fungus Botrytis cinerea.89 The phenolic xanthoxylin isolated from the leaves of Melicope sp. (order Sapindales, family Rutaceae) exhibited antifungal activity against the fungi Candida albicans and Penicillium expansum with minimum inhibitory amounts of 25 and 15 μg, respectively.90 The flavonoid quercetin-3-methyl ether isolated from the leaves of Cistus laurifolius L. (order Malvales, family Cistaceae) inhibited the growth of the Gram-negative Helicobacter pylori with a minimum inhibitory concentration of 3.9 μg/mL.91 A triterpene isolated from the leaves of Combretum imberbe Warwa (order Myrtales, family Myrtaceae) elicited antibacterial effects against Gram-negative Escherichia coli with a minimum inhibitory concentration of 16 μg/mL.92 A tetrahydroxysqualene isolated from Rhus taitensis Guill. (order Sapindales, family Anacardiaceae) was active against Mycobacterium tuberculosis with a minimum inhibitory concentration of 10 μg/mL.93 The quinoline alkaloid dictamnine isolated from the roots of Zanthoxylum wutaiense I.S. Chen (order Sapindales, family Rutaceae) elicited antitubercular activity toward Mycobacterium tuberculosis with a minimum inhibitory concentration of 30 μg/mL.94 The triterpene dysoxyhainanin A extracted from the twigs and leaves of Dysoxylum hainanense Merr. (order Sapindales, family Meliaceae) showed significant activities against Gram-positive Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, and Bacillus subtilis with minimum inhibitory concentrations of 12.5, 6.2, 12.5, and 6.2 μg/mL, respectively.95 The anthracene derivative rhodomyrtone extracted from the leaves of Rhodomyrtus tomentosa (Aiton) Hassk. (order Myrtales, family Myrtaceae) exhibited dramatic antibacterial properties against Gram-positive Staphylococcus aureus and Streptococcus mutans with minimum inhibitory concentrations of 0.3 and 0.1 μg/mL, respectively.96 Antiviral: The tannin casuarinin isolated from the bark of Terminalia arjuna (Roxb. ex DC.) Wight & Arn. (order Myrtales, family Combretaceae) abrogated the replication of the herpes simplex virus type 2 cultured in Vero cells with an IC50 value of 3.6 μM.97 The triterpene myricetic acid isolated from the stems of Hibiscus taiwanensis S.Y. Hu (order Malvales, family Malvaceae) protected H9 lymphocytic cells against human immunodeficiency virus infestation with an IC50 value of 14.9 μg/mL.98 The phenolics gallicin and dimethylcaffic acid isolated from the stems of Rhus chinensis Mill. (order Sapindales, family Anacardiaceae) protected MT-4 cells from human immunodeficiency virusinduced cell lytic effects with therapy index values of 6.3, 8.4, and 6.6, respectively.99 The triterpene dammarenolic acid isolated from the bark of Aglaia ignea Valeton ex K. Heyne (order Sapindales, family Meliaceae) inhibited human immunodeficiency virus infection potently in human epithelial cervical cancer (Hela) cells with an IC50 value of 0.4 μg/ mL.100 Ellagitannins isolated from the whole Tuberaria lignosa Samp. (order Malvales, family Cistaceae) was antiviral against the human immunodeficiency virus in MT-2infected cells with an IC50 value of 2.3 μg/mL.101 The coumarin derivative daphnoretin isolated from the roots of Wikstroemia indica (L.) C.A. Mey. (order Malvales, family

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Thymeleaceae) inhibited the replication of the respiratory syncytial virus in vitro with an IC50 value of 5.8 μg/mL.102 Parasiticidal: A coumarin derivative isolated from the aerial parts of Grewia bilamellata Gagnep. (order Malvales, family Malvaceae) exhibited an antiplasmodial property against Plasmodium falciparum with an IC50 value of 5.5 μM.103 A flavonoid isolated from the leaves of Calycolpus warscewiczianus O. Berg (order Myrtales, family Myrtaceae) demonstrated some levels of activity against Plasmodium falciparum with an IC50 value of 14.5 μM.104 Oleanolic acid isolated from Miconia ligustroides (DC.) Naudin (order Myrtales, family Melastomataceae) displayed trypanocidal activity against Trypanosoma cruzi with an IC50 value of 12.8 μM.105 The triterpene simalikalactone D isolated from the leaves of Quassia amara L. (order Sapindales, family Simaroubaceae) was toxic for Plasmodium falciparum with an IC50 value of 10 nM.106 The flavonoid isoquercitrin isolated from the aerial parts of Helianthemum glomeratum (Lag.) Lag. ex DC. (order Malvales, family Cistaceae) exhibited antiprotozoal activity against Entamoeba histolytica and Gardia lamblia with IC50 values of 14.7 and 47.5 μg/mL, respectively.107 The triterpene dysobinin isolated from Chisocheton sp. (order Sapindales, family Meliaceae) exhibited an antiplasmodial property against Plasmodium falciparum with an IC50 value of 2 μg/mL.108 The quinoline alkaloid skimmiamine isolated from the stems of Esenbeckia febrifuga (A. St.-Hil.) A. Juss. ex Mart. (order Sapindales, family Rutaceae) exhibited an antiplasmodial property with an IC50 value of 59 μM.109 The triterpene bruceatin isolated from Brucea javanica (L.) Merr. (order Sapindales, family Simaroubaceae) displayed parasiticidal activity against Entomoeba histolytica, Toxoplasma gondii, Plasmodium falciparum, Babesia gibsoni, and Trypanosoma evansi with IC50 values values of 35, 11.5, 1.5, 24.4, and 73.2 nM, respectively.110 The coumarin (−)-heliettin isolated from the stem bark of Helietta apicultata Benth. (order Sapindales, family Rutaceae) displayed leishmaniacidal activity against Leishmania amazonensis, Leishmania infantum, and Leishmania braziliensis with IC50 values of 18.5, 27.4, and 21.5 μM, respectively.111 The biflavonoids sikokianin B and C extracted from the roots of Wikstroemia indica (L.) C.A. Mey. (order Malvales, family Thymeleaceae) showed parasiticidal properties against Plasmodium falciparum with IC50 values of 0.5 μg/mL.112 Antioxidant: The tannin 1,2,3,4,6-pentagalloyl-beta-d-glucopyranose isolated from Pelargonium inquinans L’Hér. ex Aiton (order Geraniales, family Geraniaceae) exhibited an antioxidant property in the 2,2-diphenyl-1-picrylhydrazyl experiment with an IC50 value of 1.1 μg/mL.113 The phenolic rosmarinic acid isolated from the whole Jussiaea repens L. (order Myrtales, family Onagraceae) exhibited noteworthy activity in the 2,2-diphenyl-1picrylhydrazyl with 100% inhibition at a dose of 50 μg/mL.114 Central nervous system: The polyphenol hopeahainol A at a dose of 10 μM isolated from Hopea exalata W.T. Lin, Y.Y. Yang, & Q.S. Hsue (order Malvales, family Dipterocarpaceae) protected rat pheochromocytoma PC12 cells against hydrogen peroxide (200 μM) insults in vitro.115 In addition, hopeahainol A inhibited the enzymatic activity of acetylcholinesterase with an IC50 value of 4.3 μM.116 Cosmetology: The saponin escin isolated from Aesculus hippocastanum L. (order Sapindales, family Sapindaceae) inhibited the enzymatic activity of hyaluronidase with an IC50 value 149.9 μM.117 The triterpene 11-keto-beta-boswellic acid obtained from the resin of members of the genus Boswellia Roxb. ex Colebr. (order Sapindales, family Burseraceae) inhibited the enzymatic activity of elastase with an IC50 value of 15 μM.118 The flavonoid quercetin isolated from Zanthoxylum piperitum DC. (order Sapindales, family Rutaceae) inhibited the enzymatic activity of tyrosinase

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Medicinal Plants of China, Korea, and Japan

with an IC50 value of 3.8 μg/mL.119 The triterpenes betulin and lupeol isolated from Guioa villosa Radlk. (order Sapindales, family Sapindaceae) inhibited the enzymatic activity of tyrosinase.120 The tannin 1,2,3,4,6-penta-O-galloyl-beta-d-glucose isolated from the fruits of Terminalia chebula Retz (order Myrtales, family Combretaceae) inhibited the enzymatic activity of elastase and hyaluronidase with IC50 values of 57 and 0.8 μg /mL, respectively.121 Brassicales and Myrtales are among the most interesting orders in terms of pharmaceutical discovery in this clade and are discussed in greater detail in this chapter.

5.2.1  Order Myrtales Juss. ex Bercht. & J. Presl, 1820 The order Myrtales includes nine families of flowering plants of which the Lythraceae is discussed here. 5.2.1.1  Family Lythraceae J. St.-Hil., 1805, nom. cons., the Loosestrife Family The family Lythraceae consists of about 25 genera and 500 species of tanniferous herbs, shrubs, or trees that have the tendency to produce piperidine, quinolizidine alkaloids, and quinones (anthraquinones and naphthoquinones). The leaves of Lythraceae are simple, thick, reddish, opposite, and without stipules. The flowers are often 4-, 6-, or 8-merous, regular, actinomorphic, strongly perigynous, and with a prominent hypanthium. The sepals are valvate and united into a tube. The petals are free, crumpled in buds, alternate with the sepals, and pinnately veined. The stamens are twice as numerous as the petals and organized into 2 whorls. The gynoecium consists of 2–6 carpels forming a compound, superior, and plurilocular ovary. A nectary disc is present. The fruits are capsular, dehiscent, and contain several oily seeds. A classical example of Lythraceae is Lawsonia inermis L. (Henna, British Pharmaceutical Codex, 1934), the dried leaves of which have been used to counteract putrefaction and to dye the skin and the hair since a remote period in the Orient.

O OH

O Lawsone

OH HO HO

O

O

OH

OH OH

O

Orobol 7-O-D-glucoside

OH

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The dyeing component of Lawsonia inermis L. is a naphthoquinone: lawsone. Other examples of Lythraceae are Lagerstroemia indica L. (crape-myrtle) and Lythrum salicaria L. (purple loosestrife) that are cultivated for decorative purposes. In Mexico, the leaves of Heimia salicifolia Link (sinicuichi) are fermented to make a beverage that causes euphoria and hallucination. Lythraceous tannins have attracted some interest because of their antitumor properties. One such tannin is woodfordin C isolated from Woodfordia fruticosa Kurz.122 Another agent of interest in the family is orobol 7-O-d-glucoside isolated from Lagerstroemia speciosa L. that inhibited the replication of several strains of human rhinoviruses.123 Trapa natans L. is discussed in this section. 5.2.1.1.1  Trapa natans L. [From Latin trapa = thistle, and natare = to swim] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Water chestnut, ou ling (Chinese), po pyeong ma reum (Korean). Synonyms: Trapa acornis Nakano, Trapa amurensis Flerow, Trapa amurensis var. komarovii Skvortsov, apa arcuata S.H. Li & Y.L. Chang, Trapa bicornis Osbeck, Trapa bicornis var. acornis (Nakano) Z.T. Xiong, Trapa bicornis var. bispinosa (Roxb.) Nakano, Trapa bicornis var. cochinchinensis (Lour.) Steenis, Trapa bicornis var. quadrispinosa (Roxb.) Z.T. Xiong, Trapa bicornis var. taiwanensis (Nakai) Z.T. Xiong, Trapa bispinosa Roxb., Trapa bispinosa var. iinumae Nakano, Trapa chinensis Lour., Trapa cochinchinensis Lour., Trapa dimorphocarpa Z.S. Diao, Trapa japonica Flerow, Trapa japonica var. jeholensis (Nakai) Kitag., Trapa japonica var. longicollum Z.T. Xiong, Trapa japonica var. magnicorona Z.T. Xiong, Trapa japonica var. tuberculifera (V.N. Vassil.) Tzvelev, Trapa jeholensis Nakai, Trapa korshinskyi V.N. Vassil., Trapa litwinowii V.N. Vassil., Trapa litwinowii var. chihuensis S.F. Guan & Q. Lang, Trapa manshurica Flerow, Trapa manshurica fo. komarovi (Skvortsov) S.H. Li & Y.L. Chang, Trapa manshurica var. bispinosa Flerow, Trapa natans fo. quadrispinosa (Roxb.) Makino, Trapa natans var. amurensis (Flerow) Kom., Trapa natans var. bicornis (Osbeck) Makino, Trapa natans var. bispinosa (Roxb.) Makino, Trapa natans var. japonica Nakai, Trapa natans var. pumila Nakano ex Verdc., Trapa natans var. quadrispinosa (Roxb.) Makino, Trapa potaninii V.N.  Vassil., Trapa pseudoincisa Nakai, Trapa pseudoincisa var. aspinosa Z.T. Xiong, Trapa pseudoincisa var. complana Z.T. Xiong, Trapa pseudoincisa var. nanchangensis W.H. Wan, Trapa pseudoincisa var. potaninii (V.N. Vassil.) Tzvelev, Trapa quadrispinosa Roxb., Trapa quadrispinosa var. yongxiuensis W.H. Wan, Trapa saissanica (Flerow) V.N. Vassil., Trapa sibirica Flerow, Trapa sibirica var. saissanica Flerow, Trapa sibirica var. ussuriensis Flerow, Trapa taiwanensis Nakai, Trapa tranzschelii V.N. Vassil., Trapa tuberculifera V.N. Vassil. Habitat: This strange perennial floating herb grows in the swamps and slow rivers of China, Taiwan, India, Indonesia, Japan, Korea, Laos, Malaysia, Pakistan, the Philippines, Russia, Thailand, Vietnam, Africa, Australia, North America, Iran, and Europe. The fruits are used in specialty dishes, particularly in Chinese cooking. Diagnosis: The stems of Trapa natans L. are 0.5 cm in diameter. The petiole is 5–20 cm long, stout, swollen distally, and hairy. The blade is glossy, dark green above, purplish beneath, deltoid, 3 cm × 6 cm to 5 cm × 10 cm, broadly cuneate at the base, and dentate. The petals are white and 0.5–1 cm long. The fruits are woody, eery, smooth, dark brown, 1.5 cm × 3 cm, and with 2–4 horns (Figure 5.6). Medicinal uses: In China, the fruits are cooked and eaten to break fever. In Cambodia, Laos, and Vietnam, the fruits are roasted and are eaten to break fever and to mitigate headache.

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FIGURE 5.6  Trapa natans L. (From Det.: E. Topa. Flora Moldaviae and Dobrogeae Exsiccata. A Horto Botanico Universitatis “Al. I. Cuza” Iassiensis Edita. Loc.: Moldavia, Iasi. In lacu Rutura prope pag. Mir. Cesti. Alt.: 200 m. Date: August 2, 1968.)

Pharmacology: Apparently unknown. The antipyretic and analgesic effects of the plant could involve a lignan, cis-hinokiresinol, that is widespread in the genus Trapa L. An extract of Trapa bispinosa Roxb. showed, for instance, an antioxidant effect in the 2,2-diphenyl-1-picrylhydrazyl experiment likely because of cis-hinokiresinol.124,125 Besides, cis-hinokiresinol potently inhibited the generation of beta-hexosaminidase by rat basophilic leukemia (RBL-2H3) cells stimulated with immunoglobulin E, achieving an IC50 value of 98 μM.126

CH2

OH

OH

O

HO H3C

cis-Hinokiresinol

N H Acetaminophen

cis-Hinokiresinol isolated from a lily, Anemarrhena asphodeloides Bunge (order Liliales, family Liliaceae), significantly inhibited the enzymatic activity of cyclooxygenase-2 and inducible nitric oxide synthase in murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.127 Kosuge and coworkers128 isolated a cytotoxic agent from the fruits of Trapa natans L. Bioresource: In vitro pharmacological study of cis-hinokiresinol for its effect on neurodegeneration. The next clade discussed in this chapter is the order Brassicales.

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5.2.2  Order Brassicales Bromhead, 1838 The order Brassicales consists of 17 families of flowering plants of which the Brassicaceae is ­discussed here. 5.2.2.1  Family Brassicaceae Burnett, 1835, nom. cons., the Mustard Family The family Brassicaceae (or Cruciferae) is a vast and successful clade that consists of about 350 genera and 3000 species of peculiar annual or perennial pungent herbs. Brassicaceae are botanically characterized by their cross-shaped corolla and chemically characterized by the production of glucosinolates. Brassicaceae are not tanniferous. The leaves are simple, without stipules, often glaucous, fleshy, and alternate or opposite. The blade is dissected, soft, and dull green. The inflorescence is a raceme. The flowers are yellow, white, or purple, bisexual, and actinomorphic. The calyx consists of 4 sepals that are imbricate in two opposite pairs. The corolla consists of 4 petals that are imbricate in two opposite pairs. The androecium consists of 6 stamens, the 2 outer ones shorter than the 4 inner ones (tetradynamous). The anthers are bilocular and open lengthwise. The gynoecium consists of a pair of carpels united into a sessile and a single-celled ovary divided by a wall. The fruits are capsular. A large number of vegetables such as Brassica oleracea L. (cabbage), Brassica nigra (L.) Koch. (mustard), and Raphanus sativus L. (radish) belong to the Brassicaceae family. Cheiranthus cheiri L. (wallflower) and Lunaria rediviva L. (honesty) are ornamental plants. Armoracia rusticana P. Gaertn., B. Mey., & Scherb. (horseradish) and Raphanus raphanistrum L. (wild radish) can be fatal to livestock and are known to induce bloody vomiting and diarrhea in humans if ingested in excessive quantities. The pungent taste of Brassicaceae is due to volatile isothiocyanates that irritate the skin and mucosa. In addition, isothiocyanates have attracted a great deal of interest on account of their ability to boost the enzymatic activity of detoxification enzymes, including phase II enzyme, glutathione S-transferase, and quinone reductase, hence the protection against cancer. One such isothiocyanate is 4-methylsulphinyl butyl isothiocyanate obtained from broccoli that promotes the anticarcinogen marker enzyme quinone reductase in murine hepatoma (Hepa) cells. Brassicaceous plants afford several pharmaceutical products. Rape oil (British Pharmaceutical Codex, 1954) is the fixed oil extracted from Brassica napus var oleifera DC. It has been used as liniment and is also used as edible oil. Black mustard (British Pharmaceutical Codex,1949) consists of the dried seeds of Brassica nigra (L.) W.D.J. Koch that have been used as an emetic and a counterirritant. Expressed mustard oil (British Pharmaceutical Codex, 1954) is that extracted from black mustard seeds. It has been used as a mild rubefacient for the chest and rheumatic joints. Volatile mustard oil distilled from black mustard seeds (British Pharmaceutical Codex, 1949) is an extremely powerful irritant used as a counterirritant and a rubefacient. Brassica nigra (L.) W.D.J. Koch is the first plant discussed in this section. 5.2.2.1.1  Brassica nigra (L.) W.D.J. Koch [From Latin brassica = cabbage, and nigra = black] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Black mustard, hei jie (Chinese). Basionym: Sinapis nigra L. Synonyms: Brassica sinapoides Roth, Crucifera sinapis E.H.L. Krause, Mutarda nigra (L.) Bernh., Sisymbrium nigrum (L.) Prantl. Habitat: This annual herb grows in Afghanistan, India (specifically Kashmir), Kazakhstan, Nepal, Pakistan, Russia, Sikkim, Vietnam, North Africa, South West Asia, Europe, and China. Diagnosis: Brassica nigra (L.) W.D.J. Koch is 1.5 m tall. The stems are erect and branched. The petiole is 10 cm long. The blade is spatulate and 5 cm × 1 cm to 25 cm × 10 cm. The pedicels are slender, erect, and 0.5 cm long. The sepals are oblong and 0.5 cm long. The petals are yellow, membranaceous, 1 cm × 0.5 cm, and round at the apex. The filaments

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Medicinal Plants of China, Korea, and Japan

FIGURE 5.7  Brassica nigra (L.) W.D.J. Koch.

are 0.5 cm long. The anthers are oblong and 0.1 cm long. The fruits are linear, 2 cm × 0.2 cm, tetragonal, sessile, and enclose up to 5 seeds. The seeds are dark brown, globose, tiny, and reticulate (Figure 5.7). Medicinal uses: Expressed mustard oil extracted from the seeds (British Pharmaceutical Codex, 1954) has been used as a mild rubefacient for the chest and rheumatic joints. Volatile mustard oil distilled from the seeds (British Pharmaceutical Codex, 1949) is extremely irritating and has been used as a counterirritant and rubefacient. In China, the seeds are used to treat colds, stomach disorders, abscesses, rheumatism, and lumbago. The leaves are used to treat inflammation of the bladder and to check bleeding. The oil extracted from the seeds is used externally to treat allergies and ulcers. Pharmacology: Brassica nigra (L.) W.D.J. Koch contains the glucosinolate sinigrine that releases allyl isothiocyanate—an irritant and vesicant, hence its use as a counterirritant against rheumatism, lumbago, skin eruption, and ulcer. Allyl isothiocyanate is a well-­ recognized antimicrobial agent that works against a variety of microorganisms, including foodborne pathogens such as Gram-negative Escherichia coli, hence the use of the plant

CH2 HO

O S OH OH OH Sinigrine

N

OSO3–

Superorder Rosanae Takht., 1967

235

as an antiseptic.129 Besides, sinigrine abated the formation of dimethylhydrazine-induced aberrant crypt foci in rat colon. Bioresource: Chemopreventive neutraceuticals. Brassica oleracea L. var. gongyloides L. is discussed next.130 5.2.2.1.2  Brassica oleracea L. var. gongylodes L. [From Latin brassica = cabbage, and oleracea = resembling garden herbs or vegetables used in cooking] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Wild cabbage, cauliflower, cabbage, broccoli, ye gan lan (Chinese), jul gi yang bae chu (Korean). Habitat: It is cultivated as a perennial vegetable in West Europe. Diagnosis: Brassica oleracea L. var. gongyloides L. is glaucous and can grow to height of 2 m. The stems are erect, hard, and fleshy. The petiole grows up to a length of 30 cm. The blade is ovate, 40 cm × 15 cm, and pinnatifid. The upper leaves are sessile, ovate, 10 cm × 5 cm, and amplexicaul. The raceme is a fleshy head. The sepals are oblong, 0.8 cm × 0.15 cm to 1.5 cm × 0.27 cm, and erect. The petals are yellow, 1.8 cm × 0.8 cm to 2.5 cm × 1.2 cm, ovate, and round at the apex. The filaments are 0.8–1.2 cm long. The anthers are oblong and 0.2–0.4 cm long. The fruits are linear or hooked, 4 cm × 0.3 cm to 8 cm × 0.4 cm, and have 10–20 seeds that are dark brown and minute (Figure 5.8). Medicinal uses: In China, the leaves are eaten to cure fatigue and to treat indigestion. Pharmacology: Glucosinolates and their isothiocyanate produced by Brassica species are well known to prevent carcinogenesis.131 The juice obtained from leaves of several cultivars of Brassica oleracea L. compromised the growth of human breast adenocarcinoma (MCF-7) cells.132

FIGURE 5.8  Brassica oleracea L. var. gongylodes L. (From Flora of China. Date: September 1, 1928.)

236

Medicinal Plants of China, Korea, and Japan O

O S

H3C

C

S N

Sulforaphane

H3C

O

O

O

S

S

O O

CH3

Busulfan

Besides, an extract of the plant abrogated the survival of colorectal cancer (HT-29) cells and induced both glutathione S-transferase and quinone reductase in rodent bladder tissues in vivo on probable account of sulforaphane.133−135 Intraperitoneal administration of sulforaphane (500 μg/ dose/animal/day) in rodents increased the number of total white blood cells, bone marrow cellularity, and the number of alpha-esterase positive cells.136 In addition, pretreatment of peritoneal macrophages with sulforaphane inhibited bacterial lipopolysaccharide-induced generation of tumor necrosis factor-alpha, interleukin-1b, and cyclooxygenase-2.137 The juice of the plant and glucosinolates abrogated the survival of Gram-negative Salmonella enteritidis, Escherichia coli, Grampositive Listeria monocytogenes, and Candida albicans cultured in vitro.138,139 Bioresource: In vitro pharmacological study of the juice of the plant as chemopreventive neutraceuticals. Glucosinolates are found in Cardamine flexuosa With., discussed next. 5.2.2.1.3  Cardamine flexuosa With. [From Greek kardamis = for a kind of cress, and from Latin flexuosa = tortuous] History: This plant was first formally described in An Arrangement of British Plants by William Withering in 1796. Withering (1741–1799) was a British botanist. Common names: Wavy bitter-cress, wan qu sui mi ji (Chinese), hwang-sae-naeng I (Korean). Synonyms: Barbarea arisanensis (Hayata) S.S. Ying, Cardamine arisanensis Hayata, Cardamine debilis D. Don, Cardamine flexuosa subsp. debilis O.E. Schulz, Cardamine flexuosa var. debilis (O.E. Schulz) T.Y. Cheo & R.C. Fang, Cardamine flexuosa var. occulata (Hornem.) O.E. Schulz, Cardamine flexuosa var. ovatifolia T.Y. Cheo & R.C. Fang, Cardamine hirsuta subsp. flexuosa (With.) Hook. f., Cardamine hirsuta var. flaccida Franch., Cardamine hirsuta var. omeiensis T.Y. Cheo & R.C. Fang, Cardamine hirsuta var. sylvatica (Link) Hook. f. & T. Anderson, Cardamine occulata Hornem., Cardamine scutata subsp. flexuosa (With.) H. Hara, Cardamine sylvatica Link, Cardamine zollingeri Turcz., Nasturtium obliquum Zoll. Habitat: It is a little herb native to Europe that has spread in China, Bangladesh, Bhutan, India (specifically Kashmir), Indonesia, Japan, Korea, Laos, Malaysia, Burma, Nepal, Pakistan, the Philippines, Thailand, Vietnam, and America. It grows in moist shady places. Diagnosis: The stems of Cardamine flexuosa With. are erect. The basal blade is 5–10 cm long and lobed. The pedicels are 0.5–1.5 cm long and slender. The sepals are oblong and 0.2 cm long. The petals are pure white, spatulate, and 0.5 cm × 0.1 cm. The androecium comprises 6 stamens. The filaments are 0.2 cm long. The anthers are ovate, white, and minute. The fruits are linear, 2.5 cm × 0.1 cm, and green. The seeds are brown and minute (Figure 5.9). Medicinal uses: In Korea, the seeds are eaten to relieve cough and to treat indigestion. Pharmacology: Apparently unknown. Cardamine flexuosa With. probably generates some glucosinolates, the isothiocyanates of which may account for some counterirritant effects.140 Note that an extract of Cardamine angulata Hook. inhibited the replication of the herpes simplex virus cultured in vitro.141 One might be curious to look for antiviral agents in this plant.

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FIGURE 5.9  Cardamine flexuosa With. (From Coll.: N. Fukuoka & F. Konta. Plantae Japonicae Exsiccatae. No. 199. Ex Herbario Universitatis Kyotoensis. Loc.: Japan, Honshu, Kyoto, at the vicinity of Shizuhara, north of Kyoto City, in rice fields. Date: April 19, 1964.)

Bioresource: Phytochemical and pharmacological investigations of antiviral agent(s). Glucosinolates occur in Descurainia sophia (L.) Webb ex Prantl., discussed next. 5.2.2.1.4  Descurainia sophia (L.) Webb ex Prantl [After Francois Descurain (1658–1740), a French botanist, and pharmacist, and Greek sophia = ​ wisdom] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Flixweed, herb Sophia, bo niang hao (Chinese), Jae ssuk (Korean). Basionym: Sisymbrium sophia L. Synonyms: Hesperis sophia (L.) Kuntze, Sisymbrium parviflorum Lam., Sisymbrium tripinnatum DC., Sophia parviflora (Lam.) Standl., Sophia sophia (L.) Britton. Habitat: This leafy annual herb grows by roadsides, in waste places, and disturbed sites and is found in Taiwan, Afghanistan, Bhutan, Japan, India (specifically Kashmir), Kazakhstan, Korea, Kyrgyzstan, Mongolia, Nepal, Pakistan, Russia, Tajikistan, Turkmenistan, Uzbekistan, North Africa, South West Asia, and Europe. Diagnosis: Descurainia sophia (L.) Webb ex Prantl is 1 m tall. The stems are erect. The leaves are pinnatisect and 15 cm × 8 cm. The petiole is 0.1–2 cm long. The upper cauline leaves are sessile. The pedicels are 1 cm long. The sepals are yellowish, oblong, and 0.2 cm long. The petals are yellow, lanceolate, and 0.2 cm long. The filaments are 0.2 cm long. The anthers are minute. The fruits are linear and up to 2 cm long. The seeds are numerous, reddish brown, oblong, and minute (Figure 5.10). Medicinal uses: In China, the seeds are soothing, and used as a laxative and to break fever.

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FIGURE 5.10  Descurainia sophia (L.) Webb ex Prantl. (From Leg. and Det.: V. Slonovschi and A. Coman. Flora Moldaviae and Dobrogeae Exsiccatam. A Horto Botanico Universitatis “Al I. Cuza” Iassiensis Editam. Loc.: Moldavia, ditr. Iasi. In loco dicto “Gradina Botanica Iasi” Alt.: 120 m. Date: June 3, 1969.)

Constituents: Descurainia sophia (L.) Webb ex Prantl is known to contain descuraic acid sinapic acid, descurainolides A and B, descurain, flanonoid glycosides, sinapic acid ethyl ester, 3,4,5-trimethoxyl-cinnamic acid, cis-beta-ocimene, menthol, and glucosinolates.142−147 H3CO

COOH

HO

OCH3 Sinapic acid

Pharmacology: Sinapic acid inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor-alpha, and interleukin-1b by macrophages stimulated with bacterial lipopolysaccharides.148 O

O H2N

OH

H3CO

OH

HO OCH3 Gamma amino butyric acid

Sinapic acid

Superorder Rosanae Takht., 1967

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Moreover, sinapic acid given to rodents at a dose of 4 mg/kg, administered orally, exhibited anxiolytic properties in the elevated plus-maze experiment and the hole-board experiment through a mechanism involving gamma amino butyric acid.149 Bioresource: In vitro pharmacological study of sinapic acid for its effect on neurodegeneration. The next plant discussed in this section is Draba nemorosa L. 5.2.2.1.5  Draba nemorosa L. [From Greek draba = acrid, and Latin nemorosa = growing in groves or woods] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Woodland whitlow grass, ting li (Chinese), Kkot da ji (Korean). Synonyms: Crucifera nemorosa (L.) E.H.L. Krause, Draba dictyota Greene, Draba nemoralis Ehrh., Draba nemorosa var. brevisilicula Zapal., Draba nemorosa var. hebecarpa Lindblom, Draba nemorosa var. latifolia M. Bieb. ex Kuntze, Draba nemorosa var. leiocarpa Lindblom, Tomostima nemorosa (L.) Lunell. Habitat: It is a discrete annual weed found in the Alpine tundras of China, Afghanistan, Japan, India (specifically Kashmir), Korea, Kazakhstan, Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, Uzbekistan, South West Asia, Europe, and North America. Diagnosis: The stems of Draba nemorosa L. are erect and densely hairy. The basal leaves are arranged into a rosette. The blade is oblong, 2 cm × 1 cm, hairy, cuneate at the base, dentate, and obtuse at the apex. The cauline leaves are sessile. The racemes are densely flowered. The sepals are ovate, 0.1 cm long, and hairy. The petals are yellow, spatulate, 0.1 cm long, and emarginate at the apex. The filaments are 0.1 cm long. The anthers are broadly ovate and minute. The fruits are oblong, up to 1 cm long, and encloses several tiny seeds that are reddish brown and ovate (Figure 5.11). Medicinal uses: In China and Japan, this plant is boiled in water and the liquid obtained is drunk to excite the discharge of urine, and to treat dropsy, cough, and nausea.

FIGURE 5.11  Draba nemorosa L. (From Leg. S. Kharkevich, T. Buch. Det.: S. Kharkevich. Plantae Vasculares Orientis Extremi Rossici. Flora Exsiccata. Loc.: Russia, Primorkit territory, suburb of Vladivostok, Academic town, roadsides, in mass. Date: May 18, 1976.)

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Medicinal Plants of China, Korea, and Japan

Constituents: The seeds contain sinapine iodine and sulforaphane.150,151 Pharmacology: Kaempferol glycosides and cardenolides isolated from the seeds abrogated the survival of human lung adenocarcinoma epithelial (A549), and human skin melanoma (SK-MEL-2) cells cultured in vitro.152 The seeds of Draba nemorosa L. contain series of sinapic acid glycosides that showed some levels of antioxidant effects in the 2,2-diphenyl1-picrylhydrazyl experiment.153 H3CO

I–

CH3 N+

CH3

O

HO H3CO

CH3

O Sinapine iodine

Bioresource: Phytochemical and pharmacological investigations and diuretic agent(s). The next plant discussed in this section is Isatis tinctoria L. 5.2.2.1.6  Isatis tinctoria L. [From Latin isatis = a herb with a milky juice used in healing wounds, a coloring plant, woad, and tinctoria = used in dyeing] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Dyer’s woad, European Indigo, song lan (Chinese), dae-cheong (Korean). Synonyms: Isatis indigotica Fortune, Isatis oblongata var. yezoensis Y.L. Chang, Isatis tinctoria var. indigotica (Fortune) T.Y. Cheo & K.C. Kuan, Isatis tinctoria var. yezoensis (Ohwi) Ohwi, Isatis yezoensis Ohwi. Habitat: This tall biennal herb grows in the waste grounds and open lands of Japan, Kazakhstan, Korea, Mongolia, Pakistan, Russia, Tajikistan, Uzbekistan, South West Asia, and Europe. Diagnosis: The stems of Isatis tinctoria L. are glaucous, 1 m tall, and paniculately branched. The basal leaves are rosulate. The petiole is 0.5–5.5 cm long. The blade is oblong, glaucous, 5 cm × 1.5 cm to 15 cm × 3.5 cm, attenuate at the base, and obtuse at the apex. The middle cauline leaves are sessile. The blade is oblong, 3 cm × 0.5 cm to 7 cm × 2.5 cm, glaucous, fleshy, amplexicaul at the base, and acute at the apex. The inflorescence is a raceme. The sepals are oblong, tiny, and glabrous. The petals are yellow, lanceolate, 0.2 cm × 1 cm, attenuate at the base, and obtuse at the apex. The filaments are 0.2 cm long. The anthers are oblong and minute. The fruits are black, oblong, and minute (Figure 5.12). Medicinal uses: In China, this plant is used to break fever and to treat typhoid, measles, and influenza. O

H N

O H N N H



HN

O

O Indigo



Indirubin

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Superorder Rosanae Takht., 1967

FIGURE 5.12  Isatis tinctoria L. (From Det.: Emil Almqvist. Duplum ex Herb. W. Naturhistorisches Museum Wien. Loc.: Austria. Date: July 16, 1911.)

HO

O

O

O

O

NH

OH HO O Isatan B

Pharmacology: Isatis tinctoria L. is anti-inflammatory: a lipophilic extract of the plant elicited anti-inflammatory activities both in the carrageenan-induced paw edema experiment and in the 12-O-tetradecanoylphorbol-13-acetate-induced ear edema experiment.154 Alkaloids may account for this effect as this plant contains series of alkaloids with butyrylcholinesterase and lipoxygenase inhibitory activity.155

O

O

O

N

N

O N

OH

N

O

CH3 Tryptanthrin

Camptothecin

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Medicinal Plants of China, Korea, and Japan

One such alkaloid is tryptanthrin that exhibited a dramatic inhibitory activity on prostaglandin and leukotriene synthesis and on inducible nitric oxide synthase.156 Another possible anti-inflammatory agent in this plant is indolinone that inhibited compound 48/80-induced mast cell degranulation in vitro.157 The plant has been used as a source of blue dye in Europe from a very remote period. The Celts collected the leaves that were reduced into a paste and dried. Bran, water, and urine added to the paste led to the blue dye that has been used for dyeing the skin (Celts warriors) and clothes. The precursor of the dye is the glycoside isatan A that provides indigo and indirubin after fermentation.158 Indirubin was remarkably cytotoxic against human promyelocytic leukemia (HL-60) cells and mitigated the replication of the swine pseudorabies virus cultured in vitro.159 One could frame the hypothesis that the plant is used to treat typhoid, measles, and influenza because of indigo and indirubin. Bioresource: In vitro pharmacological study of tryptanthrin for its effect on cancer. The next plant discussed in this section is Lepidium sativum L. 5.2.2.1.7  Lepidium sativum L. [From Greek lepidion = a little scale, and Latin sativum = that which is sown] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Garden cress, jia du xing cai (Chinese), keun da dak naeng I (Korean). Synonyms: Crucifera nasturtium E.H.L. Krause, Nasturtium sativum (L.) Moench. Habitat: It is a peculiar annual herb found in the wet spots of China, Afghanistan, India (specifically Kashmir), Japan, Kazakhstan, Kyrgyzstan, Nepal, Pakistan, Russia, Tajikistan, Turkmenistan, Uzbekistan, Vietnam, North Africa, South West Asia, and Europe. This plant is also cultivated as a vegetable. Diagnosis: The stems of Lepidium sativum L. are erect, simple, and whitish at the base. The petiole is 1–5 cm long. The blade is pinnatifid and 2–8 cm × 1–3 cm. The cauline leaves are petiolate. The sepals are oblong, 0.1 cm long, and hairy below. The petals are white, spatulate, 2.5 cm × 0.7 cm to 3.5 cm × 0.1 cm, and membranaceous. The androecium comprises 6 stamens. The filaments are 0.2 cm long. The anthers are oblong and minute. The fruits are oblong, 0.5 cm long, round at the base, broadly winged, and reddish. The seeds are reddish, oblong, and minute (Figure 5.13). Medicinal use: In India, the seeds are used to excite the discharge of urine.

O

N

H3CO HO Cl

O

N



NH

N Lepidine

NH

N

HO



R Phenylimidazole

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Superorder Rosanae Takht., 1967

FIGURE 5.13  Lepidium sativum L.

Pharmacology: An extract of Lepidium sativum L. lowered the glycemia of streptozotocininduced diabetic rodents via the inhibition of renal glucose reabsorption.160,161 This effect is probably mediated by the imidazole alkaloids lepidine, and lepidine B, C, D, E, and F that are found in the plant.162 In fact, lepidine isolated from Lepidium ruderales L. induced hypoglycemia in alloxan-induced diabetic rodents.163 One can infer that imidazole alkaloids account for the diuretic property of the plant as 4-chloro-2-phenylimidazole-5-acetic acid derivatives have been patented as diuretics (United States patent no. 4582847).

N

C

S

Benzylisothiocyanate

In addition, Lepidium sativum L. contains glucotropaeolin and benzylisothiocyanate that protected rodents against 2-amino-3-methyl-imidazo[4,5-f] quinoline-induced damage of the colon and liver.164,165 Besides, the seeds of the plant promote the healing of broken bones and abortion in rodents.166,167 Bioresource: In vitro pharmacological study of lepidine as a diuretic for its effect on hypertension. The next plant discussed in this section is Raphanus sativus L. 5.2.2.1.8  Raphanus sativus L. [From Greek raphanos = quick-appearing, and from Latin sativus = that which is sown] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist.

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Medicinal Plants of China, Korea, and Japan

Common names: Radish, luo bo (Chinese), daikon (Japanese), mu (Korean). Synonyms: Raphanus acanthiformis J.M. Morel ex sasaki, Raphanus acanthiformis var. raphanistroides (Makino) Hara, Raphanus chinensis Mill., Raphanus macropodus H. Lév., Raphanus niger Mill., Raphanus raphanistroides (Makino) Nakai, Raphanus raphanistrum subsp. sativus (L.) Schmalh., Raphanus raphanistrum var. sativus (L.) Beck, Raphanus raphanistrum var. sativus (L.) Domin, Raphanus sativus fo. raphanistroides Makino, Raphanus sativus var. macropodus (H. Lév.) Makino, Raphanus sativus var. raphanistroides (Makino) Makino, Raphanus taquetti H. Lév. Habitat: It is an annual or biennial prostrate herb native to the Mediterranean region and is cultivated throughout the temperate world as a vegetable. Diagnosis: The root of Raphanus sativus L. is fleshy, ovoid or globose or elongate, white, pink, red, or black, 1 cm × 0.5 cm to 10 cm × 2 cm, and edible. The petiole is 1–30 cm long. The blade is oblong, 2 cm × 1 cm to 60 cm × 20 cm, pinnatisect, dentate, and obtuse at the apex. The cauline leaves are subsessile and dentate. The sepals are oblong and 1 cm × 0.2 cm. The petals are purple red, pink, or white, spatulate, membranaceous, 2 cm × 0.5 cm, and obtuse at the apex. The filaments are slender and 1 cm long. The anthers are 0.2 cm long and sagittate at the base. The fruits are fusiform and contain several ovoid seeds that are 0.5 cm in diameter (Figure 5.14). Medicinal uses: In Japan, this plant is used to treat rheumatism, to break fever, to stop diarrhea and to treat indigestion. In China, this plant is used to break fever, to heal burns, to treat indigestion, dysentery, cough, dropsy, apoplexy, and to excite the discharge of urine. In Cambodia, Laos, and Vietnam, this plant is used to treat stomach cancer and swollen breasts. In Europe, the plant has been used as a drug for liver diseases. Pharmacology: The leaves of Raphanus sativus L. contain catechin, protocatechuic acid, syringic acid, vanillic acid, ferulic acid, sinapic acid, o-coumaric acid, myricetin, and quercetin that showed some levels of antioxidant effect.168 Note that catechin, sinapic acid, myricetin, and quercetin probably impart to the plant its anti-inflammatory and antipyretic properties.148,169,170 Besides, this plant is hepatoprotective and chemopreventive.171−173 Raphanus sativus L. contains 4-methylthio-3-butenyl isothiocyanate that is cytotoxic, antioxidant, and antimutagenic, and that is probably accountable for the anticancer property mentioned above.174,175 Isothiocyanates are counterirritants and may play a key role in the external use of the plant. S C N

S

CH3

4-Methylthio-3-butenyl isothiocyanate

The diuretic property of this plant is confirmed: an extract of Raphanus sativus L. elicited antiurolithiatic activity in the zinc disc implantation experiment and augmented the 24 h urine volume as compared to a control.176 Besides, rodents fed with Raphanus sativus L. developed symptoms of hypothyroidism including an increase in weight of the thyroid gland, a decrease in thyroid peroxidase activity, and a decrease in thyroid hormone level.177 Bioresource: In vitro pharmacological study of 4-methylthio-3-butenyl isothiocyanate for its effect on cancer. The next plant discussed in this section is Thlaspi arvense L.

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FIGURE 5.14  Raphanus sativus L. (From Coll.: S. Lau. Flora of Kwangtung. Herbarium of Lingnan Natural History Survey and Museum Lingnan University, Canton, China. Loc.: China, Yung-Yuen and Ying Tak districts, rare, level land, forest. Date: Jan 8, 1933.)

5.2.2.1.9  Thlaspi arvense L. [From Greek thlaspi = cresses, and Latin arvense = of the fields] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Stinkweed, field pennycress, xi ming (Chinese), gunbainazuna (Japanese), mal naeng I (Korean). Synonyms: Crucifera thlaspi E.H.L. Krause, Teruncius arvense (L.) Lunell. Habitat: This strange annual herb grows in the grasslands of China, Afghanistan, Bhutan, India (specifically Kashmir), Japan, Kazakhstan, Korea, Kyrgyzstan, Mongolia, Nepal, Pakistan, Russia, Tajikistan, Turkmenistan, Uzbekistan, Africa, South West Asia, Australia, and America. Diagnosis: The stems of Thlaspi arvense L. are erect and 50 cm tall. The petiole of the basal leaves is 0.5–3.5 cm long. The blade is oblanceolate, 1 cm × 0.5 cm to 5 cm × 2 cm, attenuate at the base, toothed, and round at the apex. The middle cauline leaves are sessile, oblong, 1.5 cm × 0.5 cm to 5 cm × 1.5 cm, amplexicaul at the base, and laxly serrate. The inflorescence is a terminal raceme. The sepals are ovate, 0.2 cm × 0.1 cm, and whitish. The petals are white, spatulate, 0.3 cm × 0.1 cm, clawed at the base, and emarginate at the apex. The filaments are 0.2 cm long. The anthers are ovate, yellow, and minute. The fruit pedicel is at a right angle from the stem. The fruits are somewhat heart-shaped, 1 cm × 0.5 cm, round at the base, and deeply emarginated at the apex. The seeds are blackish brown and ovoid (Figure 5.15). Medicinal uses: In China, the seeds are used to treat eye diseases and to cure fatigue.

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FIGURE 5.15  Thlaspi arvense L. (From Leg.: J. Nikta. Flora Cechoslovaca Exsiccata. Ed. Cur. Section Botanica Musei Nationalis Pragae. Centuria I. No. 13. Loc.: Czechoslovakia, Bohemia centralis: In agris prope vicum Pruhonice, haud procul Pragam. Alt.: 300 m. Date: October 28, 1958.)

Pharmacology: Thlaspi arvense L. elaborates series of flavonoids of which apigenin, luteolin, and isovitexin are anti-inflammatory.178,179 Apigenin given to rodents abated the level of inflammatory cell infiltration, airway hyper-responsiveness, and total immunoglobulin E levels in an allergen-induced airway inflammation experiment.180 OH OH HO

O

OH

O

Luteolin

Besides, luteolin abrogated the secretion of tumor necrosis factor-alpha, interleukin-8, and interleukin-6 by mast cells stimulated with phorbol 12-myristate 13-acetate.181 Moreover, isovitexine isolated from Acacia pennata Willd. (order Fabales, family Fabaceae) inhibited the enzymatic activity of cyclooxygenase-1 and cyclooxygenase-2.182 In addition, isovitexin impaired the generation of H2O2 and nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides.183

247

Superorder Rosanae Takht., 1967 OH HO

HO

O

O HO HO

OH

OH

O

Isovitexin

Bioresource: In vitro pharmacological study of luteolin as an anti-inflammatory agent. Anti-inflammatory agents are common in the next clade: the superorder Saxifraganae, discussed in Chapter 6.

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91. Ustün O, Ozçelik B, Akyön Y, Abbasoglu U, Yesilada E, 2006, Flavonoids with anti-Helicobacter pylori activity from Cistus laurifolius leaves. J Ethnopharmacol; 108(3):457–461. 92. Angeh JE, Huang X, Sattler I, Swan GE, Dahse H, Härtl A, Eloff JN, 2007, Antimicrobial and antiinflammatory activity of four known and one new triterpenoid from Combretum imberbe (Combretaceae). J Ethnopharmacol; 110(1):56–60. 93. Noro JC, Barrows LR, Gideon OG, Ireland CM, Koch M, Matainaho T, Piskaut P, Pond CD, Bugni TS, 2008, Tetrahdroxysqualene from Rhus taitensis shows antimycobacterial activity against Mycobacterium tuberculosis. J Nat Prod; 71(9):1623–1624. 94. Huang HY, Ishikawa T, Peng CF, Tsai IL, Chen IS, 2008, Constituents of the root wood of Zanthoxylum wutaiense with antitubercular activity. J Nat Prod; 71(7):1146–1151. 95. He XF, Wang XN, Gan LS, Yin S, Dong L, Yue JM, 2008, Two novel triterpenoids from Dysoxylum hainanense. Org Lett; 10(19):4327–4330. 96. Limsuwan S, Trip EN, Kouwen TR, Piersma S, Hiranrat A, Mahabusarakam W, Voravuthikunchai SP, van Dijl JM, Kayser O, 2009, Rhodomyrtone: A new candidate as natural antibacterial drug from Rhodomyrtus tomentosa. Phytomed; 16(6–7):645–651. 97. Cheng HY, Lin CC, Lin TC, 2002, Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Antiviral Res; 55(3):447–455. 98. Wu PL, Wu TS, He CX, Su CH, Lee KH, 2005, Constituents from the stems of Hibiscus taiwanensis. Chem Pharm Bull (Tokyo); 53(1):56–59. 99. Wang RR, Gu Q, Wang YH, Zhang XM, Yang LM, Zhou J, Chen JJ, Zheng YT, 2008, Anti-HIV-1 activities of compounds isolated from the medicinal plant Rhus chinensis. J Ethnopharmacol; 117(2):249–526. 100. Esimone CO, Eck G, Nworu CS, Hoffmann D, Uberla K, Proksch P, 2010, Dammarenolic acid, a secodammarane triterpenoid from Aglaia sp. shows potent anti-retroviral activity in vitro. Phytomed; 17(7):540–547. 101. Bedoya LM, Abad MJ, Sánchez-Palomino S, Alcami J, Bermejo P, 2010, Ellagitannins from Tuberaria lignosa as entry inhibitors of HIV. Phytomed; 17(1):69–74. 102. Ho WS, Xue JY, Sun SS, Ooi VE, Li YL, 2010, Antiviral activity of daphnoretin isolated from Wikstroemia indica. Phytother Res; 24(5):657–661. 103. Ma C, Zhang HJ, Tan GT, Hung NV, Cuong NM, Soejarto DD, Fong HH, 2006, Antimalarial compounds from Grewia bilamellata. J Nat Prod; 69(3):346–350. 104. Torres-Mendoza D, González J, Ortega-Barría E, Heller MV, Capson TL, McPhail K, Gerwick WH, Cubilla-Rios L, 2006, Weakly antimalarial flavonol arabinofuranosides from Calycolpus warszewiczianus. J Nat Prod; 69(5):826–828. 105. Cunha WR, Crevelin EJ, Arantes GM, Crotti AE, Andrade e Silva ML, Furtado NA, Albuquerque S, Ferreira Dda S, 2006, A study of the trypanocidal activity of triterpene acids isolated from Miconia species. Phytother Res; 20(6):474–478. 106. Bertani S, Houël E, Stien D, Chevolot L, Jullian V, Garavito G, Bourdy G, Deharo E, 2006, Simalikalactone D is responsible for the antimalarial properties of an Amazonian traditional remedy made with Quassia amara L. (Simaroubaceae). J Ethnopharmacol; 108(1):155–157. 107. Calzada F, Alanís AD, 2007, Additional antiprotozoal flavonol glycosides of the aerial parts of Helianthemum glomeratum. Phytother Res; 21(1):78–80. 108. Maneerat W, Laphookhieo S, Koysomboon S, Chantrapromma K, 2008, Antimalarial, antimycobacterial and cytotoxic limonoids from Chisocheton siamensis. Phytomed; 15(12):1130–1134. 109. Dolabela MF, Oliveira SG, Nascimento JM, Peres JM, Wagner H, Póvoa MM, de Oliveira AB, 2008, In vitro antiplasmodial property of extract and constituents from Esenbeckia febrifuga, a plant traditionally used to treat malaria in the Brazilian Amazon. Phytomed; 15(5):367–372. 110. Bawm S, Matsuura H, Elkhateeb A, Nabeta K, Subeki, Nonaka N, Oku Y, Katakura K, 2008, In vitro antitrypanosomal activities of quassinoid compounds from the fruits of a medicinal plant, Brucea javanica. Vet Parasitol; 158(4):288–294. 111. Ferreira ME, de Arias AR, Yaluff G, de Bilbao NV, Nakayama H, Torres S, Schinini A, Guy I, Heinzen H, Fournet A, 2010, Antileishmanial activity of furoquinolines and coumarins from Helietta apiculata. Phytomed; 17(5):375–378. 112. Nunome S, Ishiyama A, Kobayashi M, Otoguro K, Kiyohara H, Yamada H, Omura S, 2004, In vitro antimalarial activity of biflavonoids from Wikstroemia indica. Planta Med; 70(1):76–78. 113. Piao X, Piao XL, Kim HY, Cho EJ, 2008, Antioxidative activity of geranium (Pelargonium inquinans Ait) and its active component, 1,2,3,4,6-penta-O-galloyl-beta-d-glucose. Phytother Res; 22(4):534–538. 114. Huang HL, Li DL, Li XM, Xu B, Wang BG, 2007, Antioxidative principals of Jussiaea repens: An edible medicinal plant. Int J Food Sc Technol; 42:1219–1227.

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115. Shi DH, Wu JH, Ge HM, Tan RX, 2009, Protective effect of hopeahainol A, a novel acetylcholinesterase inhibitor, on hydrogen peroxide-induced injury in PC12 cells. Env Toxicol Pharmacology; 28(1):30–36. 116. Ge HM, Zhu CH, Shi da H, Zhang LD, Xie DQ, Yang J, Ng SW, Tan RX, 2008, Hopeahainol A: An acetylcholinesterase inhibitor from Hopea hainanensis. Chemistry; 14(1):376–381. 117. Facino RM, Carini M, Stefani R, Aldini G, Saibene L, 1995, Anti-elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: Factors contributing to their efficacy in the treatment of venous insufficiency. Arch Pharm (Weinheim); 328(10):720–724. 118. Safayhi H, Rall B, Sailer ER, Ammon HP, 1997, Inhibition by boswellic acids of human leukocyte elastase. J Pharmacol Exp Ther; 281(1):460–463. 119. Jeong CH, Shim KH, 2004, Tyrosinase inhibitor isolated from the leaves of Zanthoxylum piperitum. Biosci Biotechnol Biochem; 68(9):1984–1987. 120. Magid AA, Voutquenne-Nazabadioko L, Bontemps G, Litaudon M, Lavaud C, 2008, Tyrosinase inhibitors and sesquiterpene diglycosides from Guioa villosa. Planta Med; 74(1):55–60. 121. Kim SJ, Sancheti SA, Sancheti SS, Um BH, Yu SM, Seo SY, 2010, Effect of 1,2,3,4,6-penta-O-galloylbeta-d-glucose on elastase and hyaluronidase activities and its type II collagen expression. Acta Pol Pharm; 67(2):145–150. 122. Kuramochi-Motegi A, Kuramochi H, Kobayashi F, Ekimoto H, Takahashi K, Kadota S, Takamori Y, Kikuchi T, 1992, Woodfruticosin (woodfordin C), a new inhibitor of DNA topoisomerase II. Experimental antitumor activity. Biochem Pharmacol; 44(10):1961–1965. 123. Choi HJ, Bae EY, Song JH, Baek SH, Kwon DH, 2010, Inhibitory effects of orobol 7-O-d-glucoside from banaba (Lagerstroemia speciosa L.) on human rhinoviruses replication. Lett Appl Microbiol; 51(1):1–5. 124. Kim BJ, Kim JH, Kim HP, Heo MY, 1997, Biological screening of 100 plant extracts for cosmetic use (II): Antioxidative activity and free radical scavenging activity. Int J Cosmet Sci; 19(6):299–307. 125. Song MC, Yang HJ, Bang MH, Kim DK, Jeong TS, Kim JP, Baek NI, 2007, Antioxidant and antiatherogenic activity of cis-hinokiresinol from Trapa pseudoincisa. Arch Pharm Res; 30(11):1392–1397. 126. Bae EA, Park EK, Yang HJ, Baek NI, Kim DH, 2006, Hinokiresinol inhibits immunoglobulin E-induced mouse passive cutaneous anaphylaxis reaction. Planta Med; 72(14):1328–1330. 127. Lim H, Nam JW, Seo EK, Kim YS, Kim HP, 2009, (−)-Nyasol (cis-hinokiresinol), a norneolignan from the rhizomes of Anemarrhena asphodeloides, is a broad spectrum inhibitor of eicosanoid and nitric oxide production. Arch Pharm Res; 32(11):1509–1514. 128. Kosuge T, Yokota M, Sugiyama K, Okamoto A, Saito M, Yamamoto T, 1986, Studies on Chinese medicines used for cancer. III. Cytotoxic constituent against HeLa cells in the fruit of Trapa bispinosa Roxb. Yakugaku Zasshi; 106(2):183–185. 129. Luciano FB, Holley RA, 2009, Enzymatic inhibition by allyl isothiocyanate and factors affecting its antimicrobial action against Escherichia coli O157:H7. Int J Food Microbiol; 131(2–3):240–245. 130. Smith TK, Lund EK, Johnson IT, 1998, Inhibition of dimethylhydrazine-induced aberrant crypt foci and induction of apoptosis in rat colon following oral administration of the glucosinolate sinigrin. Carcinogenesis; 19(2):267–273. 131. Assayed ME, Abd El-Aty AM, 2009, Cruciferous plants: Phytochemical toxicity versus cancer chemoprotection. Mini Rev Med Chem; 9(13):1470–1478. 132. Brandi G, Schiavano GF, Zaffaroni N, De Marco C, Paiardini M, Cervasi B, Magnani M, 2005, Mechanisms of action and antiproliferative properties of Brassica oleracea juice in human breast cancer cells. J Nutr; 135(6):1503–1509. 133. Mas S, Crescenti A, Gassó P, Deulofeu R, Molina R, Ballesta A, Kensler TW, Lafuente A, 2007, Induction of apoptosis in HT-29 cells by extracts from isothiocyanates-rich varieties of Brassica oleracea. Nutr Cancer; 58(1):107–114. 134. Zhang Y, Munday R, Jobson HE, Munday CM, Lister C, Wilson P, Fahey JW, Mhawech-Fauceglia P, 2006, Induction of GST and NQO1 in cultured bladder cells and in the urinary bladders of rats by an extract of broccoli (Brassica oleracea italica) sprouts. J Agric Food Chem; 54(25):9370–9376. 135. Zhang Y, Talalay P, Cho CG, Posner GH, 1992, A major inducer of anticarcinogenic protective enzymes from broccoli: Isolation and elucidation of structure. Proc Natl Acad Sci U S A; 89(6):2399–2403. 136. Thejass P, Kuttan G, 2007, Immunomodulatory activity of Sulforaphane, a naturally occurring isothiocyanate from broccoli (Brassica oleracea). Phytomed; 14(7–8):538–545. 137. Wen L, Wu RT, Wu T, Khor TO, Wang H, Kong AN, 2008, Sulforaphane suppressed lipopolysaccharideinduced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway. Biochem Pharmacol; 76(8):967–973.

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138. Brandi G, Amagliani G, Schiavano GF, De Santi M, Sisti M, 2006, Activity of Brassica oleracea leaf juice on foodborne pathogenic bacteria. J Food Prot; 69(9):2274–2279. 139. Sisti M, Amagliani G, Brandi G, 2003, Antifungal activity of Brassica oleracea var. botrytis fresh aqueous juice. Fitoterapia; 74(5):453–458. 140. Louda SM, Rodman JE, 1983, Concentration of glucosinolates in relation to habitat and insect herbivory for the native crucifer Cardamine cordifolia. Biochem System Ecol; 11(3):199–207. 141. McCutcheon AR, Roberts TE, Gibbons E, Ellis SM, Babiuk LA, Hancock REW, Towers GHN, 1995, Antiviral screening of British Columbian medicinal plants. J Ethnopharmacol; 49(2–1):101–110. 142. Sun K, Li X, Li W, Liu JM, Wang JH, Sha Y, 2006, A new nor-lignan from the seeds of Descurainia sophia. Nat Prod Res; 20(6):519–522. 143. Sun K, Li X, Liu JM, Wang JH, Li W, Sha Y, 2005, A novel sulphur glycoside from the seeds of Descurainia sophia (L.). J Asian Nat Prod Res; 7(6):853–856. 144. Sun K, Li X, Li W, Wang J, Liu J, Sha Y, 2004, Two new lactones and one new aryl-8-oxa-bicyclo[3,2,1] oct-3-en-2-one from Descurainia sophia. Chem Pharm Bull (Tokyo); 52(12):1483–1486. 145. Wang AQ, Wang XK, Li JL, Cui XY, 2004, Isolation and structure identification of chemical constituents from the seeds of Descurainia sophia (L.) Webb ex Prantl. Yao Xue Xue Bao;39(1):46–51 146. Li J, Liu X, Dong F, Xu J, Zheng Y, Shan W, 2010, Determination of the volatile composition in essential oil of Descurainia sophia (L.) Webb ex Prantl (Flixweed) by gas chromatography/mass spectrometry (GC/MS). Molecules; 15(1):233–240. 147. Lockwood GB, Afsharypuor S, 1986, Comparative study of the volatile aglucones of glucosinolates from in vivo and in vitro grown Descurainia sophia and Alyssum minimum using gas chromatography-mass spectrometry. J Chromatography A; 356:438–440. 148. Yun KJ, Koh DJ, Kim SH, Park SJ, Ryu JH, Kim DG, Lee JY, Lee KT, 2008, Anti-inflammatory effects of sinapic acid through the suppression of inducible nitric oxide synthase, cyclooxygase-2, and proinflammatory cytokines expressions via nuclear factor-kappaB inactivation. J Agric Food Chem; 56(21):10265–10272. 149. Yoon BH, Jung JW, Lee JJ, Cho YW, Jang CG, Jin C, Oh TH, Ryu JH, 2007, Anxiolytic-like effects of sinapic acid in rodent. Life Sci; 81(3):234–240. 150. Kung HP, Huang WY, 1949, Chemical investigation of Draba nemorosa L. The isolation of sinapine iodide. J Am Chem Soc; 71(5):1836–1837. 151. Lihong W, Juan L, Guiyan W, Juan D, 2010, Extract ion technology and HPLC determination of sulforaphane in Draba nemorosa L. var. leiocarpa Lindl. Chinese Traditional and Herbal Drugs; 27(4):316–319. 152. Moon SS, Rahman MA, Manir MM, Jamal Ahamed VS, 2010, Kaempferol glycosides and cardenolide glycosides, cytotoxic constituents from the seeds of Draba nemorosa (Brassicaceae). Arch Pharm Res; 33(8):1169–1173. 153. Rahman M and Moon SS, 2007, Antioxidant polyphenol glycosides from the plant Draba nemorosa. Bull Korean Chem Soc; 28(5):827–831. 154. Recio MC, Cerdá-Nicolás M, Potterat O, Hamburger M, Ríos JL, 2006, Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin. Planta Med; 72(6):539–546. 155. Ahmad I, Fatima I, 2008, Butyrylcholinesterase, lipoxygenase inhibiting and antifungal alkaloids from Isatis tinctoria. J Enzyme Inhib Med Chem; 23(3):313–316. 156. Oberthür C, Hamburger M., 2004, Tryptanthrin content in Isatis tinctoria leaves—A comparative study of selected strains and post-harvest treatments. Planta Med; 70(7):642–645. 157. Kiefer S, Mertz AC, Koryakina A, Hamburger M, Küenzi P, 2010, (E,Z)-3-(3′,5′-dimethoxy-4′-hydroxybenzylidene)-2-indolinone blocks mast cell degranulation. Eur J Pharm Sci; 40(2):143–147. 158. Oberthür C, Graf H, Hamburger M, 2004, The content of indigo precursors in Isatis tinctoria leaves— A comparative study of selected accessions and post-harvest treatments. Phytochem; 65(24): 3261–3268. 159. Hsuan SL, Chang SC, Wang SY, Liao TL, Jong TT, Chien MS, Lee WC, Chen SS, Liao JW, 2009, The cytotoxicity to leukemia cells and antiviral effects of Isatis indigotica extracts on pseudorabies virus. J Ethnopharmacol; 123(1):61–67. 160. Eddouks M, Maghrani M, Zeggwagh A, Michel JB, 2005, Study of the hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal and diabetic rats. J Ethnopharmacol; 97(2):391–395. 161. Eddouks M, Maghrani M, 2008, Effect of Lepidium sativum L. on renal glucose reabsorption and urinary TGF-beta 1 levels in diabetic rats. Phytother Res; 22(1):1–5. 162. Maier UH, Gundlach H, Zenk MH, 1998, Seven imidazole alkaloids from Lepidium sativum. Phytochem; 49(6):1791–1795.

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163. Ivorra MD, Payá M, Villar A, 1989, A review of natural products and plants as potential antidiabetic drugs. J Ethnopharmacol; 27(3):243–275. 164. Gil V, MacLeod AJ, 1980, Studies on glucosinolate degradation in Lepidium sativum seed extracts. Phytochem; 19(7):1369–1374. 165. Kassie F, Rabot S, Uhl M, Huber W, Qin HM, Helma C, Schulte-Hermann R, Knasmüller S, 2002, Chemoprotective effects of garden cress (Lepidium sativum) and its constituents towards 2-amino-3methyl-imidazo[4,5-f]quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions. Carcinogenesis; 23(7):1155–1161. 166. Juma AH, 2007, The effects of Lepidium sativum seeds on fracture-induced healing in rabbits. Med Gen Med; 9(2):23. 167. Sharief M, Gani ZH, 2004, Garden cress Lepidium sativum seeds as oral contraceptive plant in mice. Saudi Med J; 25(7):965–966. 168. Beevi SS, Narasu ML, Gowda BB, 2010, Polyphenolics profile, antioxidant and radical scavenging activity of leaves and stem of Raphanus sativus L. Plant Foods Hum Nutr; 65(1):8–17. 169. Hirao K, Yumoto H, Nakanishi T, Mukai K, Takahashi K, Takegawa D, Matsuo T, 2010, Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells. Life Sci; 86(17–18):654–660. 170. Park HH, Lee S, Son HY, Park SB, Kim MS, Choi EJ, Singh TS et al., 2008, Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res; 31(10):1303–1311. 171. Chaturvedi P, Machacha CN, 2007, Efficacy of Raphanus sativus in the treatment of acetaminopheninduced hepatotoxicity in albino rats. Br J Biomed Sci; 64(3):105–108. 172. Salah-Abbès JB, Abbès S, Haous Z, Oueslati R, 2009, Raphanus sativus extract prevents and ameliorates zearalenone-induced peroxidative hepatic damage in Balb/c mice. J Pharm Pharmacol; 61(11):1545–1554. 173. Barillari J, Iori R, Papi A, Orlandi M, Bartolini G, Gabbanini S, Pedulli GF, Valgimigli L, 2008, Kaiware Daikon (Raphanus sativus L.) extract: A naturally multipotent chemopreventive agent. J Agric Food Chem; 56(17):7823–7830. 174. Papi A, Orlandi M, Bartolini G, Barillari J, Iori R, Paolini M, Ferroni F, Grazia Fumo M, Pedulli GF, Valgimigli L, 2008, Cytotoxic and antioxidant activity of 4-methylthio-3-butenyl isothiocyanate from Raphanus sativus L. (Kaiware Daikon) sprouts. J Agric Food Chem; 56(3):875–883. 175. Nakamura Y, Iwahashi T, Tanaka A, Koutani J, Matsuo T, Okamoto S, Sato K, Ohtsuki K, 2001, 4-(Methylthio)-3-butenyl isothiocyanate, a principal antimutagen in daikon (Raphanus sativus; Japanese white radish). J Agric Food Chem; 49(12):5755–5760. 176. Vargas R, Perez RM, Perez S, Zavala MA, Perez C, 1999, Antiurolithiatic activity of Raphanus sativus aqueous extract on rats. J Ethnopharmacol; 68(1–3):335–338. 177. Chandra AK, Mukhopadhyay S, Ghosh D, Tripathy S, 2006, Effect of radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats. Indian J Exp Biol; 44(8):653–661. 178. Onyilagha J, Bala A, Hallett R, Gruber M, Soroka J, Westcott N, 2003, Leaf flavonoids of the cruciferous species, Camelina sativa, Crambe spp., Thlaspi arvense and several other genera of the family Brassicaceae. Biochem System Ecol; 31(11):1309–1322. 179. Pedras MSC, Chumala PB, Suchy M, 2003, Phytoalexins from Thlaspi arvense, a wild crucifer resistant to virulent Leptosphaeria maculans: Structures, syntheses and antifungal activity. Phytochem; 64(5):949–956. 180. Li RR, Pang LL, Du Q, Shi Y, Dai WJ, Yin KS, 2010, Apigenin inhibits allergen-induced airway inflammation and switches immune response in a murine model of asthma. Immunopharmacol Immunotoxicol; 32(3):364–370. 181. Kang OH, Choi JG, Lee JH, Kwon DY, 2010, Luteolin isolated from the flowers of Lonicera japonica suppresses inflammatory mediator release by blocking NF-kappaB and MAPKs activation pathways in HMC-1 cells. Molecules; 15(1):385–398. 182. Dongmo AB, Miyamoto T, Yoshikawa K, Arihara S, Lacaille-Dubois MA, 2007, Flavonoids from Acacia pennata and their cyclooxygenase (COX-1 and COX-2) inhibitory activities. Planta Med; 73(11):1202–1207. 183. Lin CM, Huang ST, Liang YC, Lin MS, Shih CM, Chang YC, Chen TY, Chen CT, 2005, Isovitexin suppresses lipopolysaccharide-mediated inducible nitric oxide synthase through inhibition of NF-kappa B in mouse macrophages. Planta Med; 71(8):748–753.

6

Superorder Saxifraganae Reveal, 1994*

6.1  ORDER SAXIFRAGALES BERCHT. & J. PRESL, 1820 Members of the Saxifraganae and the Rosanae share an ancestor from which they have inherited the ability to accumulate tannins, flavonoids, terpenes, and, to a lesser extent, some alkaloids of pharmacological importance. Cytotoxic: The “daphniphyllum alkaloids” daphniglaucins A and B isolated from the leaves of Daphniphyllum glaucescens Bl. (family Daphniphyllaceae) were cytotoxic against mouse lymphocytic leukemia L1210 cells with IC50 values of 2.7 and 3.9 μg/mL, respectively, and human nasopharyngeal carcinoma (KB) cells (IC50 values of 2 and 10 μg/mL, respectively) in vitro.1 Antibacterial: The flavonoid glycosides gossypetin-7-O-l-rhamnopyranoside and rhodioflavonoside isolated from the dried stems of Rhodiola rosea L. (family Crassulaceae) inhibited the growth of Gram-positive Staphylococcus aureus with minimum inhibitory concentrations of 50 and 100 μg/mL, respectively.2 Parasiticidal: A labdane diterpene isolated from Aeonium lindleyi Webb & Berthel. (family Crassulaceae) exhibited parasiticidal activity against Leishmania tropica and Leishmania braziliensis with IC50 values of 77 and 68 μM, respectively.3 Cosmetology: The cosmetological properties of Saxifragales are yet to be evaluated. One can infer that tannins might play a significant role as antiageing agents. The order Saxifragales consists of nine families of flowering plants of which the Haloragaceae is discussed here.

6.1.1  F amily Haloragaceae R.Br. (in M. Flinders, 1814), nom. cons., the Water Milfoil Family The family Haloragaceae consists of 9 genera and over 100 species of widespread aquatic herbs. Halogaraceae produce ellagitannins, proanthocyanidins, and ellagic acid. The leaves are alternate, opposite, or whorled, very diverse in form and size, and without stipules. The inflorescence is a spike, a raceme, or a panicle. The flowers are small and tetramerous. The sepals are valvate and persistent in fruits. The petals are larger than the sepals and deciduous. The androecium comprises 8 stamens arranged in 2 whorls. The anthers are tetrasporangiate and dithecal and open by longitudinal slits. The gynoecium consists of 4 carpels united to form a compound, inferior ovary, with 4 locules and distinct styles. The fruits are small, nut-like, or drupaceous. An example of Haloragaceae is the Myriophyllum aquaticum (Vell.) Verdc. (parrot’s feather), a common aquarium plant. The pharmacological potentials of this family are yet to be explored. Halocharis hispida (Schrenk ex C. A. Mey.) Bunge produces an antifungal substance isolated and characterized by Bondarenko and coworkers.4 The plant examined in this section is Myriophyllum spicatum L. *

The superorder Saxifraganae consists of the orders Cynomoriales and Saxifragales.

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6.1.1.1  Myriophyllum spicatum L. [From Greek myrios = numberless, and phyllon = leaf, and from Latin spicatum = with flowers in spikes] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Eurasian water-milfoil, spiked water-milfoil, sui zhuang hu wei zao (Chinese), mul su se mi (Korean). Habitat: This filamentous aquatic perennial is found in the stagnant waters of China and ­cosmopolitan warm areas. Diagnosis: The stems of Myriophyllum spicatum L. are much branched, leafy, and grow to a length of 2.5 m. The submerged leaves are arranged in 4 or 5 whorls, pectinate, and 3 cm × 1 cm to 3.5 cm × 5 cm. The segments are arranged in 15 pairs, filiform, and 1–1.5 cm long. The inflorescence is a 6–10-cm-long terminal spike of 4-whorled flowers. The male flowers are minute and present a broadly campanulate calyx that is 0.1 cm long. The corolla presents 4 petals that are pale pink, elliptical, and 0.2 cm long. The androecium comprises 8 stamens. The female flowers are minute and present a tubiform calyx that is 0.1 cm long. The fruits are cylindrical, 0.2 cm × 0.1 cm, and made of 4 locules (Figure 6.1). Medicinal uses: In China, this plant is used to break fever and to treat flu and dysentery. Constituents: Myriophyllum spicatum L. contains some hydrolyzable tannins including beta1,2,3-tri-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-d-glucose, the astringency of which could account for the antidysenteric use of the plant.5 Pharmacology: Antibacterial phenolic glycosides that occur in Myriophyllum verticillatum L. could be involved in the antibacterial activity of Myriophyllum spicatum L.6

FIGURE 6.1  Myriophyllum Spicatum L. (From Coll.: H. F. Sun. Flora Of China. Loc.: China, Yangtze Valley. Date: 1936.)

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Superorder Saxifraganae Reveal, 1994 HO

OH

HO

OH

O

HO

O O O

HO

O

OH

O

O

O O

HO HO

OH

O

O

HO

OH

HO

OH

OH Beta-1,2,3-tri-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-D-glucose OH HO

OH OH OH O

O O

HO HO

O

HO

O 1′-O-caffeoyl-6′-O-galloyl-beta-D-glucopyranose OH OH HO

O

OH OH 3-S-(+)-catechol

Besides, the antiviral property of the plant could be imparted to flavonoids as 3-S-(+)-catechol isolated from Ephedra sp. (order Ephedrales, family Ephedraceae) abrogated the survival of the influenza virus (H1N1) cultured in vitro.7 Bioresource: In vitro pharmacological study of beta-1,2,3-tri-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-d-glucose for its effect on skin ageing. Flavonoids abound in the next clade: the superorder Santalanae, discussed in Chapter 7.

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REFERENCES

1. Kobayashi J, Takatsu H, Shen YC, Morita H, 2003, Daphniglaucins A and B, novel polycyclic quaternary alkaloids from Daphniphyllum glaucescens. Org Lett; 5(10):1733–1736. 2. Ming DS, Hillhouse BJ, Guns ES, Eberding A, Xie S, Vimalanathan S, Towers GH, 2005, Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytother Res; 19(9):740–743. 3. Kennedy ML, Cortés F, Piñero JE, Castanys S, López-Arencibia A, Gamarro F, Bazzocchi IL, Jiménez IA, 2010, Leishmanicidal and reversal multidrug resistance constituents from Aeonium lindleyi. Planta Med; 77(1):77–80. 4. Bondarenko AS, Petrenko GT, Meshcheriakov AO, 1970, Antifungal antibiotic from the fodder plant Halocharis hispida (C.A.M.) Bqe. Mikrobiol Zh; 32(4):522–523. 5. Leu E, Krieger-Liszkay A, Goussias C, Gross EM, 2002, Polyphenolic allelochemicals from the aquatic angiosperm Myriophyllum spicatum inhibits photosystem II. Plant Physiol; 130(4):2011–2018. 6. Aliotta G, Molinaro A, Monaco P, Pinto G, Previtera L, 1992, Three biologically active phenylpropanoid glucosides from Myriophyllum verticillatum. Phytochemis; 31(1):109–111. 7. Mantani N, Imanishi N, Kawamata H, Terasawa K, Ochiai H, 2001, Inhibitory effect of (+)-catechin on the growth of influenza A/PR/8 virus in MDCK cells. Planta Med; 67(3):240–243.

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Superorder Santalanae Thorne ex Reveal, 1992*

7.1  ORDER SANTALALES R.BR. EX BERCHT. & J. PRESL, 1820 The order Santalales consists of seven families of flowering plants which, like the Saxifragales, are tanniferous. Tannins, flavonoids, and lignans of pharmacological interest are present in this order. Cytotoxic: The tannin balanophotannin E isolated from Balanophora japonica Makino (family Balanophoraceae) was cytotoxic against human hepatocellular liver carcinoma (HepG2) cells with an IC50 value of 4.2 μM.1 Anti-inflammatory: A (−)-pinoresinol lignan isolated from Balanophora abbreviata Blume (family Balanophoraceae) inhibited the expression of inducible nitric oxide synthetase by murine macrophages (RAW264.7) challenged with lipopolysaccharide at a dose of 10 μM.2 Antioxidant: Catechin isolated from Misodendrum punctulatum Banks ex J.R. Forst. (family Misodendraceae) reduced the generation of thiobarbituric acid reactive substances in rat liver homogenates, with an IC50 value of 26 μg/mL.3 Hydrolyzable tannins isolated from Balanophora laxiflora Hemsl. (family Misodendraceae) exhibited antioxidant activities in the 2,2-diphenyl-1-picrylhydrazyl experiment with IC50 values below 5 μM.4 Cosmetology: The flavonoids rutin, nicotiflorin, hyperoside, and isoquercitrin isolated from Tripodanthus acutifolius (Ruiz & Pav.) Tiegh. (family Loranthaceae) inhibited the enzymatic activity of hyaluronidase with IC50 values of 1.7 μM.5 The family Loranthaceae is discussed in detail in this chapter.

7.1.1  Family Loranthaceae Juss., 1808, nom. cons., the Showy Mistletoe Family The family Loranthaceae sensu lato consists of about 70 genera and 700 species of hemiparasitic tanniferous plants growing on trees. The leaves are simple, opposite, often thick, entire, and without stipules. Flavonoids of pharmacological importance abound in this family. The flowers are often red or yellow, elongated, perfect, epigynous, regular, and arranged in various sorts of inflorescences. The calyx is a shallow cup around the summit of the ovary. The corolla consists of 5 petals that are valvate and connate below to form an orangish tube. The androecium consists of 5 stamens. The anthers are tetrasporangiate and dithecal and open by longitudinal slits. The gynoecium consists of 3–4 carpels united to form a compound, inferior, and unilocular ovary. The fruits are laticiferous berries or drupes. Classical examples of Loranthaceae are the Christmas mistletoe Viscum album L. and Phoradendron serotinum (Raf.) M. C. Johnston. Mistletoe (British Pharmaceutical Codex, 1934) consists of the dried Viscum album L. that has been used to induce vasodilation. It has also been used for its effect on hysteria, cancer, and chorea. It was administered as a soft extract in pills, or as an infusion or tincture. Besides, a dihydropyranone isolated from Tapinanthus dodoneifolius (DC.) *

The superorder Santalanae includes the single order Santalales.

259

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Medicinal Plants of China, Korea, and Japan

Danser induced the vasodilation of rat aortic rings with an IC50 value of about 81 μM.6 A diarylheptanoid isolated from Viscum coloratum (Kom.) Nakai scavenged free radicals in the electron spin resonance experiment.7 Loranthaceae are known to abound with flavonoids and triterpenes of pharmacological interest. Phoradendron reichenbachianum (Seem.) Oliv. contains the cytotoxic triterpene moronic acid.8 Note that moronic acid abrogated the survival of the herpes simplex virus, human immunodeficiency virus, and Epstein–Barr virus cultured in vitro.9 Extracts of a member of the genus Scurrula L. ­displayed remarkable cytotoxic effects against mouse fibrosarcoma (WEHI-164) cells cultured in  vitro.10 Catechin, 3,4-dimethoxycinnamyl alcohol, and 3,4,5-trimethoxycinnamyl alcohol isolated from Loranthus globiferus A. Rich. elicited noteworthy antimicrobial and cytotoxic activities.11

O

O

OH

OH

Dihydropyranone

O

HO

H

O HO

OH Mistletonone

H3C

CH3

CH3

CH3

COOH CH3

O H3C

CH3 Moronic acid

H3CO

OH

H3CO 3,4-Dimethoxycinnamyl alcohol

Rhamnetin 3-O-alpha-l-rhamnoside, quercetin 3-O-alpha-l-rhamnoside, rhamnocitrin 3-O-alpha-l-rhamnoside and kaempferol 3-O-alpha-l-rhamnoside isolated from Loranthus tanakae Franch. & Sav. abrogated the survival of human lung adenocarcinoma epithelial (A549), human

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ovary adenocarcinoma (SK-OV-3), human skin melanoma (SK-MEL-2), human glioma (XF498), and human colorectal adenocarcinoma (HCT-15) cells cultured in vitro.12 Extracts of mistletoe lowered the arterial blood pressure of rodents through a mechanism of action involving the muscarinic receptors.13 The first plant discussed in this section is Dendrophthoe pentandra (L.) Miq. 7.1.1.1  Dendrophthoe pentandra (L.) Miq. [From Greek dendro = tree, and phthoe = to waste away, and from Latin pentandra = with five stamens] History: This plant was first formally described in Mantissa Plantarum by Carl Linnaeus in 1767. Linnaeus (1707–1778) was a Swedish botanist. Common names: Daun benalu duku (Indonesian), wu rui ji sheng (Chinese). Basionym: Loranthus pentandrus L. Habitat: This hemiparasitic epiphytic shrub grows on trees in the forests of China, Cambodia, India, Indonesia, Laos, Malaysia, Burma, the Philippines, Thailand, and Vietnam. Diagnosis: Dendrophthoe pentandra (L.) Miq. is 2 m tall. The stems are grayish and lenticelled. The petiole is 1 cm long. The blade is lanceolate, 5 cm × 2.5 cm to 15 cm × 10 cm, leathery, with 2–4 pairs of secondary nerves, cuneate at the base, and acute at the apex. The inflorescence is a raceme of 3–10 flowers. The calyx is 0.2 cm long and pentadenticulate. The corolla is orange, inflated at the base, and has 5 lanceolate lobes that are 1 cm long and reflexed. The filaments are 0.4 cm long. The anthers are 0.5 cm long. The berries are ovoid, red, and 1 cm × 0.5 cm (Figure 7.1). Medicinal uses: In Vietnam, the leaves are mixed with tea to make a drink used to treat cough. In Malaysia, the leaves are boiled in water and the drink obtained is taken as a postpartum remedy. The leaves are used to heal wounds, sores, and ulcers. Constituents: Apparently unknown. Series of oleanane, lupane, and ursane triterpene saponins, as well as kaempferol-3-O-alpha-l-rhamnopyranoside and quercetin-3-O-alpha-lrhamnopyranoside have been isolated from Dendrophthoe falcata L. f.14

FIGURE 7.1  Dendrophthoe pentandra (L.) Miq. (From Herb. Mus. Paris. Loc.: Laos, Luang Baban. Date: February 26, 1932.)

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Pharmacology: Apparently unknown. An extract of Dendrophthoe falcata (L.f) Ettingsh exhibited a dramatic healing effect in the excision and wound experiments in rodents. In addition, some fractions of this plant inhibited the growth of Gram-positive Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus epidermidis, Micrococcus luteus, Bacillus subtilis, Bacillus cereus, Gram-negative Klebsiella pneumoniae, Enterobacter aerogenes, Pseudomonas aeruginosa, Serratia marcescens, and fungi Candida albicans, Candida tropicalis, Aspergillus fumigatus, and Aspergillus niger cultured in vitro.15 Note that kaempferol-3-O-alpha-l-rhamnopyranoside was found to be a ligand for estrogen receptors.14 Bioresource: Antibacterial agent(s). Macrosolen cochinchinensis (Lour.) Tiegh. is the next plant discussed in this section. 7.1.1.2  Macrosolen cochinchinensis (Lour.) Tiegh. [From Greek makros = large, and solen = a channel, and from Latin cochinchinensis = from Cochinchina] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Round-fruited mistletoes, benalu nangka, benalu belimbing (Malay), qiao hua (Chinese). Basionym: Loranthus cochinchinensis Lour. Synonyms: Elytranthe ampullacea (Roxb.) G. Don, Elytranthe ampullacea var. tonkinensis Lecomte, Elytranthe cochinchinensis (Lour.) G. Don, Elytranthe cochinchinensis var. tonkinensis (Lecomte) H.L. Li, Elytranthe fordii (Hance) Merr., Loranthus ampullaceus Roxb., Loranthus cochinchinensis Lour., Loranthus fordii Hance, Loranthus thonnerrii Engl., Macrosolen fordii (Hance) Danser, Tristerix viridiflorus (Wallich) Mart. Habitat: This parasitic shrub grows on trees in the rainforests of Bhutan, Cambodia, India, Indonesia, Malaysia, Burma, Nepal, Papua New Guinea, Thailand, and Vietnam. Diagnosis: Macrosolen cochinchinensis (Lour.) Tiegh. is 5 m tall. The stems are grayish and lenticelled. The petiole is 0.5–1 cm long. The blade is glossy, broadly elliptical, 5 cm × 2.5 cm to 10 cm × 6 cm, leathery, with 4 or 5 pairs of secondary nerves, cuneate at the base, and acute at the apex. The inflorescence is a raceme of 4–8 flowers. The calyx is elliptical and 0.2 cm long. The corolla is orange, straight, inflated in the middle, and hexagonal. The corolla lobes are lanceolate, 0.4 cm long, and reflexed. The filaments are 0.2 cm long. The anthers are 0.1 cm long. The berries are orange, globose, glossy, and 0.5 cm in diameter (Figure 7.2). Medicinal uses: In Cambodia, Laos, and Vietnam, the berries are eaten to treat cough. In Malaysia, a paste of leaves is applied to the head to assuage headache and the juice from the bark is ingested to expel the placenta. Pharmacology: Apparently unknown. The uterotonic property of the plant has not been validated yet but it can be noted that an extract of Loranthus ferrugineus Roxb. (order Santalales, family Loranthaceae) induced a dose-dependent contraction in isolated guinea pig ileum via cholinergic stimulation.16 In addition, an extract of Globimetula braunii (Engl.) Danser (order Santalales, family Loranthaceae) exhibited oxytocic activity on the uterine smooth muscle.17

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FIGURE 7.2  Macrosolen cochinchinensis (Lour.) Tiegh. (From Coll.: Dyg. Awa and B. Lee. Det.: A. Mohtar. Sarawak Forest Department. No. 50780. Loc.: Malaysia, Ulu Sg., Limbang, route to Bt. Lawi, Bario, 4th Division. Date: September 8, 1988.)

Bioresource: Muscarinic or adrenergic agent(s). Macrosolen robinsonii (Gamble) Danser is discussed next. 7.1.1.3  Macrosolen robinsonii (Gamble) Danser [From Greek makros = large, and solen = a channel, and for Robinson, unknown] History: This plant was first formally described in Bulletin of Miscellaneous Information Kew by James Sykes Gamble in 1913. Gamble (1847–1925) was a British botanist. Common name: Duan xu qiao hua (Chinese). Basionym: Elytranthe robinsonii Gamble. Habitat: This epiphyte shrub grows on trees in the rainforests of Cambodia, Laos, Vietnam, Thailand, and Malaysia. Diagnosis: Macrosolen robinsonii (Gamble) Danser is 1 m tall. The stems are grayish and lenticelled. The petiole is 0.2–0.5 cm long. The blade is elliptical, 8 cm × 2.5 cm, leathery, cuneate at the base, and acuminate at the apex. The inflorescence is an umbel of 2–3 flowers. The calyx is elliptical and 0.2 cm long. The corolla is orange, inflated, and has 5 lobes that are lanceolate, 0.6 cm long, and reflexed. The filaments are 0.2 cm long and the anthers are minute. Medicinal uses: In Cambodia, Laos, and Vietnam, the leaves are used to make a beverage taken to excite the discharge of urine and to flatten enlarged abdomens. Pharmacology: Apparently unknown. One could frame the hypothesis that muscarinic agonists present in Macrosolen robinsonii (Gamble) Danser activate the muscle of the bladder (detrusor) to contract to expel urine. Note that syringin and coniferin extracted from Viscum album L. (order Santalales, family Loranthaceae) produced constriction of isolated rat aortic rings.18 In addition, syringin promoted the secretion of insulin through a mechanism involving acetylcholine and muscarinic M3 receptors in pancreatic cells.19 Is syringin the diuretic agent of Macrosolen robinsonii (Gamble) Danser?

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Medicinal Plants of China, Korea, and Japan H3CO

OH

HO

OH

O

O OCH3

OH OH Syringin

Bioresource: In vitro pharmacological study of syringin as a diuretic agent. Syringin might be involved in the medicinal uses of Macrosolen tricolor (Lecomte) Danser, discussed next. 7.1.1.4  Macrosolen tricolor (Lecomte) Danser [From Greek makros = large, and solen = a channel, and from Latin tricolor = with 3 colors] History: This plant was first formally described in Notulae Systematicae. Herbier du Museum de Paris by Paul Henri Lecomte in 1914. Lecomte (1856–1934) was a French botanist. Common name: San se qiao hua (Chinese). Basionym: Elytranthe tricolor Lecomte. Habitat: This parasitic shrub grows on trees in the rainforests of Cambodia, Laos, and Vietnam. Diagnosis: Macrosolen tricolor (Lecomte) Danser is 50 cm tall. The stems are grayish and lenticelled. The petiole is 0.2 cm long. The blade is obovate, 3.5 cm × 1 cm to 5.5 cm × 2 cm, leathery, with 2–3 pairs of secondary nerves, cuneate at the base, and round at the apex. The inflorescence is an umbel of 2 flowers. The calyx is elliptical and 0.2 cm long. The corolla is reddish green, tubular, 0.7 cm long, and has 5 reflexed lobes. The filaments are 0.3 cm long. The anthers are 0.2 cm long. The berries are dark purple, globose, glossy, 0.7 cm in diameter, and smooth (Figure 7.3).

FIGURE 7.3  Macrosolen tricolor (Lecomte) Danser. (From Coll.: W. T. Tsang. Flora of Indo-China. Herbarium of the Botanical Survey. Lingnan University. Canton, China. 4th Indo-China Expedition. No. 30701. Loc.: Ho Yung Shan and vicinity, Tien-yen, Tonkin. Date: October 13–November 22, 1940.)

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Medicinal use: In Cambodia, Laos, and Vietnam, this plant is used to make a laxative beverage. Pharmacology: Apparently unknown. The purgative property of the plant has not been validated yet but it can be noted that an extract of Loranthus ferrugineus Roxb. (order Santalales, family Loranthaceae) produced a dose-dependent contractile effect in guinea pig ileum via cholinergic stimulation. This contraction was markedly abrogated by atropine.16 Therefore, one could frame the hypothesis that the purgative property of Macrosolen tricolor (Lecomte) Danser is the result of some spasmogenic effect of cholinergic agents. Is syringin involved here? Bioresource: Phytochemical and pharmacological investigations and muscarinic agent(s). The next plant discussed in this section is Scurrula ferruginea (Jack) Danser. 7.1.1.5  Scurrula ferruginea (Jack) Danser [From Latin scurrula = a little clown, and ferruginea = rusty red] History: This plant was first formally described in Malayan Miscellanies by William Jack in 1820. Jack (1795–1822) was a Scottish botanist. Common name: Xiu mao li guo ji sheng (Chinese). Basionym: Loranthus ferrugineus Jack. Synonym: Cichlanthus ferrugineus (Jack) Tiegh. Habitat: This epiphytic shrub is found in the forests of China, Cambodia, Indonesia, Laos, Malaysia, Burma, the Philippines, Thailand, and Vietnam. Diagnosis: Scurrula ferruginea (Jack) Danser is 1 m tall. The young stems and leaves are hairy. The petiole is 0.2–0.6 cm long. The blade is broadly elliptical, 5 cm × 2 cm to 10 cm × 5 cm, thinly leathery, with 5–8 pairs of secondary nerves, round at the base, and obtuse at the apex. The raceme is axillary and has 4–6 flowers. The calyx is ovoid, 0.4 cm long, and annular. The corolla is brown, slightly curved, tomentose, inflated at the apex, and develops 5 lanceolate lobes that are 0.4 cm long and reflexed. The filaments and the anthers are minute. The berries are pyriform, 1 cm × 0.5 cm, hairy, and contracted into a stalk at the base (Figure 7.4). Medicinal uses: In Malaysia, this plant is used as a postpartum protective remedy, and to treat malaria, to heal wounds, and to counteract snakebites. Pharmacology: Extracts of Scurrula ferruginea (Jack) Danser were antiviral against the herpes simplex virus and poliovirus and were cytotoxic against murine Lewis lung carcinoma (LL3), mouse lymphocytic leukemia (L1210), human erythromyeloblastoid leukemia (K562), human glioblastoma (U251), human prostate carcinoma (DU145), and human breast adenocarcinoma (MCF-7) cells cultured in vitro on probable account of quercetin.20,21 OH OH HO

O

OH

O Quercetin

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Medicinal Plants of China, Korea, and Japan

FIGURE 7.4  Scurrula ferruginea (Jack) Danser. (From Det.: Singapore. Forest Research Institute, Kepong, Malaysia. No. 42/38. N.B. A 767. Date: April 21, 1950.)

Besides, an extract of the plant induced vasodilation of rat thoracic aorta through a mechanism involving muscarinic receptors, nitric oxide, and prostacyclin.22 Are muscarinic flavonoids involved here? Note that an extract of Tapinanthus sessilifolius (P. Beauv.) Tiegh. (order Santalales, family Loranthaceae) abrogated the survival of Plasmodium berghei cultured in vivo.23 Bioresource: Antimalarial agent(s). The next plant discussed in this section is Scurrula parasitica L. 7.1.1.6  Scurrula parasitica L. [From Latin scurrula = a little clown, and parasitica = parasitic] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common name: Hong hua ji she (Chinese). Synonyms: Loranthus parasiticus (L.) Merr., Taxillus parasiticus (L.) S.T. Chiu. Habitat: This epiphytic shrub grows on trees in the forests of China, Taiwan, Bangladesh, Bhutan, India, Indonesia, Malaysia, Burma, Nepal, the Philippines, Thailand, and Vietnam. Diagnosis: Scurrula parasitica L. is 1 m tall. The stems and leaves are hairy when young. The stems are brownish gray and lenticelled. The leaves are opposite. The petiole is 0.5 cm long. The blade is ovate, 5 cm × 2 cm to 10 cm × 4 cm, papery, with 5–6 pairs of secondary nerves, cuneate at the base, and obtuse at the apex. The raceme is axillary and has 3–7 flowers. The calyx is turbinate and 0.2 cm long. The corolla is yellowish, curved, 1–2.5 cm long, inflated, and has 5 lanceolate lobes that are 0.8 cm long and reflexed. The filaments are 0.3 cm long. The anthers are 0.2 cm long. The berries are reddish yellow, broadly pyriform, 0.8 cm × 0.3 cm to 1 cm × 0.3 cm, and tapering at the base into a stalk (Figure 7.5).

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FIGURE 7.5  Scurrula parasitica L. (From Coll.: F.P. Metcalf and Tang Chung Chang. Det.: Danser. Flora of Fukien Province. Fukien Christian University. No. 4869. Loc.: Foochow and vicinity, grassy hillside, near water gate. Date: September 10, 1926; June 22, 1936.)

Medicinal uses: In China, this plant is used to excite the discharge of urine, to treat the lack of milk, to strengthen the bones, to reduce swellings, to lower blood pressure, to mitigate back and knee pain, and to treat liver diseases. Pharmacology: Scurrula parasitica L. contains some flavonoids that are cytotoxic against human promyelocytic leukemia (HL-60) cells.24 The analgesic and anti-inflammatory properties of the plant are not yet validated but one could think of flavonoids, as 3-R-(−)epicatechol isolated from Arceuthobium oxycedri (DC.) M. Bieb. (order Santalales, family Santalaceae) showed anti-inflammatory and analgesic properties in both the carrageenaninduced paw edema experiment and the p-benzoquinone-induced abdominal contraction experiment.25 OH OH HO

O

OH OH

3-R-(−)-epicatechol

Bioresource: In vitro pharmacological study of 3-R-(−)-epicatechol for its effect on skin ageing. The next plant discussed in this section is Taxillus kaempferi (DC.) Danser.

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Medicinal Plants of China, Korea, and Japan

7.1.1.7  Taxillus kaempferi (DC.) Danser [From Latin taxillus = a small die, and after Engelbert Kaempfer (1651–1716), German physician, traveler to Russia, Persia, Batavia, Arabia, Japan, and Java, naturalist, and chief surgeon of the East India Company from 1685 to 1693] History: This plant was first formally described in Prodromus Systematis Naturalis Regni Vegetabilis by Augustin Pyramus de Candolle in 1830. de Candolle (1778–1841) was a Swiss botanist. Common name: Xiao ye dun guo ji sheng (Chinese). Basionym: Viscum kaempferi DC. Synonym: Loranthus kaempferi Maxim. Habitat: It is a parasitic shrub that grows on trees in the forests of China, Bhutan, and Japan. Diagnosis: Taxillus kaempferi (DC.) Danser is 1 m tall. The stems are terete, hairy, grayish brown, verrucose, and lenticelled. The leaves are alternate or 2–4-fascicled on short shoots. The petiole is short. The blade is linear, 1.5 cm × 0.2 cm to 3 cm × 0.5 cm, leathery, cuneate at the base, and obtuse at thr apex. The inflorescence is an umbel of 2–3 flowers. The calyx is subglobose, 0.2 cm long, glabrous, and has 4 lobes. The corolla is red, slightly curved, glabrous, and has 5 lanceolate lobes that are 0.5 cm long and reflexed. The filaments are 0.1 cm long and the anthers are 0.4 cm long. The berries are reddish brown, glossy, ovoid, 0.5 cm in diameter, and granulose (Figure 7.6). Medicinal uses: In China, this plant is used to treat malaria, skin infection, and urogenital infection. The plant is also used to excite the discharge of urine and as a sedative. Pharmacology: The medicinal properties of Taxillus kaempferi (DC.) Danser are probably to the result of flavonoids including quercetin, avicularin, taxillusin, quercitrin, and hyperin

FIGURE 7.6  Taxillus kaempferi (DC.) Danser. (From Coll.: W.C. Cheng. Det.: Danser. Herbarium of Biological Laboratory. The Science Society of China, Nanking China. No. 4582. Loc.: China, Anhwei Wangshai. Date: October 23, 1933; 1938.)

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as well as catechin, procyanidin B-1, and procyanidin B-3.26,27 The antimalarial property of the plant might be the result of quercetin, as quercetin isolated from Diosma pilosa I.J Williams (order Sapindales, family Rutaceae) abrogated the survival of Plasmodium falciparum cultured in vitro achieving an IC50 value of 6.4 μg/mL.28 OH OH HO

O OH OH

OH

OH HO

O

OH OH Procyanidin B-1

The antiseptic property might be to the result of quercetin and catechins that are astringent and precipitate proteins.29 Besides, flavonoids may also play a role in the diuretic property of the plant, as a flavonoid mixture extracted from Spergularia purpurea Pers. (order Caryophyllales, family Caryophyllaceae) boosted water excretion in hypertensive and normal rodents.30 Moreover, quercetin isolated from Calluna vulgaris (L.) Hull (order Ericales, family Ericacea) inhibited the enzymatic activity of monoamine oxidase A with an IC50 value of about 18 μM, hence the anxiolytic property of the plant.31 Bioresource: Diuretic agent(s). The next plant discussed in this section is Viscum articulatum Burm.f. 7.1.1.8  Viscum articulatum Burm.f. [From Latin Viscum = the Latin name for mistletoe, and articulatum = articulated] History: This plant was first formally described in Flora indica: cui Accedit Series Zoophy­ torum Indicorum nec non Prodromus Florae Capensis by Nicolaas Burman in 1768. Burman (1734–1793) was a professor of botany at Amsterdam. Common name: Bian zhi hu ji sheng (Chinese). Synonyms: Aspidixia articulata (Burm. f.) Tiegh., Viscum articulatum var. dichotomum (D. Don) Kurz, Viscum dichotomum D. Don, Viscum liquidambaricola Hayata, Viscum nepalense Spreng. Habitat: This mistletoe grows on trees in the forests of China, Taiwan, Southeast Asia, and Australia. Diagnosis: Viscum articulatum Burm.f. is pendulous and 50 cm long. The stems are opposite, decussate, dichotomous, and flattened. The leaves are mere pairs of scales. The inflorescence is an axillary cyme. The male flowers are globose in buds and minute. The perianth comprises 4 little lobes. The female flowers are elliptical in buds and minute. The stigma is cushion-shaped and minute. The berries are whitish, globose, 0.3 cm in diameter, and smooth (Figure 7.7).

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FIGURE 7.7  Viscum articulatum Burm.f. (From Coll.: T.L. Yao. Forest Research Institute Malaysia. Date: January 1, 2008.)

Medicinal uses: In China, this plant cooked with meat is eaten to treat tuberculosis; it is also used to cure fatigue and to treat liver diseases. In Taiwan, this plant is used to treat neuralgia. In Cambodia, Laos, and Vietnam, this plant is boiled in water and the liquid obtained is drunk to treat bronchitis. This plant is also used to calm and to cure fatigue. Pharmacology: The triterpene oleanolic acid isolated from Viscum articulatum Burm.f., protected rodents from gentamicin-induced kidney damage.32 Previous reports have shown that oleanolic acid has antimycobacterial activity against Mycobacterium tuberculosis, hence the antitubercular effect mentioned above.33 Besides, oleanolic acid is hepatoprotective, anti-inflammatory, antitumour, antihyperlipidemic, and antiulcer.34 The calming effect of the plant may involve oleanolic acid that inhibited gamma amino butyric acid transaminase activity.35

H3C

CH3

CH3

COOH

CH3 CH3

HO H3C

CH3 Oleanolic acid

The plant is known to produce diphenylpropane glycosides, glycosidic acyl esters, and phenolic glycosides that may account for the bechic property mentioned above.36,37 Note that the plant ­augments series of flavanones that abrogated the survival of the human immunodeficiency virus cultured in vitro.37

Superorder Santalanae Thorne ex Reveal, 1992

271

Bioresource: In vitro pharmacological study of oleanolic acid and derivatives as antidiabetic agents. The next plant discussed in this section is Viscum ovalifolium DC. 7.1.1.9  Viscum ovalifolium DC. [From Latin Viscum = the Latin name for mistletoe, and ovalifolium = with oval leaves] History: This plant was first formally described in Prodromus Systematis Naturalis Regni Vegetabilis by Augustin Pyramus de Candolle in 1830. de Candolle (1778–1841) was a Swiss botanist. Common name: Liu guo hu ji sheng (Chinese). Habitat: This mistletoe grows on trees in the forests and mangroves of China, Bhutan, Cambodia, India, Indonesia, Laos, Malaysia, Burma, the Philippines, Thailand, and Vietnam. Diagnosis: Viscum ovalifolium DC. is 50 cm tall. The stems are opposite, decussate, dichotomous, and terete. The internodes are 1.5–3 cm long and swollen. The leaves are opposite. The petiole is 0.3 cm long. The blade is spatulate, 3 cm × 1.5 cm to 8.5 cm × 3.5 cm, leathery, with 3–5 nerves, and obtuse at the apex. The inflorescence is an axillary cyme. The male flowers are ovoid in buds and 0.15 cm long. The perianth comprises 4 lobes. The female flowers are elliptical in buds, 0.3 cm long, and consist of a perianth with 4 triangular lobes. The stigma is nipple-shaped. The berries are yellow, tuberculate, globose, 0.5 cm in diameter, and develop minute stalks (Figure 7.8). Medicinal uses: In Cambodia, Laos, and Vietnam, this plant is used to break fever. In Malaysia, this plant is used to treat neuralgia and itches. Pharmacology: Apparently unknown, but one could reasonably frame the hypothesis that lupeol acetate, oleanolic acid, and beta-amyrin could be accountable for the anti-inflammatory and analgesic properties listed above.38 In fact, the triterpene beta-amyrin isolated from

FIGURE 7.8  Viscum ovalifolium DC. (From Coll.: D. Middleton, S. Suddee, and C. Hemriat. Forest Herbarium of Bangkok. Harvard University Herbaria. Flora of Thailand. No. 1322. Loc.: Thailand, Prachuap Khiri Khan, Amphoe Thap Sakar, Huay Yang National Park. Bua Sawan waterfall area. 11°40.4′N–99°33.9′E. Alt.: 150 m. Date: August 26, 2002.)

272

Medicinal Plants of China, Korea, and Japan

Protium heptaphyllum (Aubl.) March. (order Sapindales, family Burseraceae) elicited analgesic effects in the acetic acid-induced abdominal writhing experiment, the formalin experiment, and the hot plate experiment, and exhibited anti-inflammatory effects in the carrageenan-induced paw edema experiment.39 H3C

CH3

CH3

CH3

CH3 CH3

HO H3C

CH3 Beta-amyrin

Bioresource: In vitro pharmacological study of beta-amyrin and derivatives for its effect on inflammation. Triterpenes are common in the next clade: the superorder Caryophyllanae, discussed in Chapter 8.

REFERENCES

1. Jiang ZH, Wen XY, Tanaka T, Wu SY, Liu Z, Iwata H, Hirose Y, Wu S, Kouno I, 2008, Cytotoxic hydrolyzable tannins from Balanophora japonica. J Nat Prod; 71(4):719–723. 2. Hosokawa A, Sumino M, Nakamura T, Yano S, Sekine T, Ruangrungsi N, Watanabe K, Ikegami F, 2004, A new lignan from Balanophora abbreviata and inhibition of lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression. Chem Pharm Bull (Tokyo); 52(10):1265–1267. 3. Desmarchelier C, del V Pacciaroni A, Abate-Daga D, Coussio J, Gil RR, Silva GL, 2005, Antioxidant and free radical scavenging activities of Misodendrum punctulatum, myzodendrone and structurally related phenols. Phytother Res; 19(12):1043–1047. 4. She GM, Zhang YJ, Yang CR, 2009, Phenolic constituents from Balanophora laxiflora with DPPH ­radical-scavenging activity. Chem Biodivers; 6(6):875–880. 5. Soberón JR, Sgariglia MA, Sampietro DA, Quiroga EN, Vattuone MA, 2010, Free radical scavenging activities and inhibition of inflammatory enzymes of phenolics isolated from Tripodanthus acutifolius. J Ethnopharmacol; 130(2):329–333. 6. Ouedraogo M, Carreyre H, Vandebrouck C, Bescond J, Raymond G, Guissou IP, Cognard C et al., 2007, Structure elucidation of a dihydropyranone from Tapinanthus dodoneifolius. J Nat Prod; 70(12): 2006–2009. 7. Yao H, Zhou GX, Wu Q, Lei GQ, Chen DF, Chen JK, Zhou TS, 2007, Mistletonone, a novel antioxidative diarylheptanoid from the branches and leaves of Viscum coloratum. Molecules; 12(3):312–317. 8. Rios MY, Salina D, Villarreal ML, 2001, Cytotoxic activity of moronic acid and identification of the new triterpene 3,4-seco-olean-18-ene-3,28-dioic acid from Phoradendron reichenbachianum. Planta Med; 67(5):443–446. 9. Chang FR, Hsieh YC, Chang YF, Lee KH, Wu YC, Chang LK, 2010, Inhibition of the Epstein–Barr virus lytic cycle by moronic acid. Antiviral Research; 85(3):490–495. 10. Murwani R, 2003, Indonesian tea mistletoe (Scurrula oortiana) stem extract increases tumour cell sensitivity to tumour necrosis factor alpha (TNFα). Phytother Res; 17(4):407–409. 11. Sadik G, Islam R, Rahman MM, Khondkar P, Rashid MA, Sarker SD, 2003, Antimicrobial and cytotoxic constituents of Loranthus globosus. Fitoterapia; 74(3):308–311. 12. Kim YK, Kim YS, Choi SU, Ryu SY, 2004, Isolation of flavonol rhamnosides from Loranthus tanakae and cytotoxic effect of them on human tumour cells. Arch Pharm Res; 27(1):44–77.

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13. Radenkovic M, Ivetic V, Popovic M, Brankovic S, Gvozdenovic L., 2009, Effects of mistletoe (Viscum album L., Loranthaceae) extracts on arterial blood pressure in rats treated with atropine sulfate and hexocycline. Clin Exp Hypertens; 31(1):11–19. 14. Mallavadhani UV, Narasimhan K, Sudhakar AV, Mahapatra A, Li W, van Breemen RB, 2006, Three new pentacyclic triterpenes and some flavonoids from the fruits of an Indian Ayurvedic plant Dendrophthoe falcata and their estrogen receptor binding activity. Chem Pharm Bull (Tokyo); 54(5):740–744. 15. Pattanayak SP, Sunita P, 2008, Wound healing, antimicrobial and antioxidant potential of Dendrophthoe falcata (L.f) Ettingsh. J Ethnopharmacol; 120(2):241–247. 16. Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Sadikun A, Ismail Z, Shah AM, Asmawi MZ, 2010, Cardiovascular activity of the n-butanol fraction of the methanol extract of Loranthus ferrugineus Roxb. Braz J Med Biol Res; 43(2):186–194. 17. Ie O, Zam N, 2008, Oxytocic properties of the aqueous extract of Globimetula braunii (Loranthaceae). Pak J Pharm Sci; 21(4):356–360. 18. Deliorman D, Ihsan Ç, Ergun F, Uyde BS, Dogan S, Buharalıoglu CK, Kanzık I, 2000, Studies on the vascular effects of the fractions and phenolic compounds isolated from Viscum album ssp. album. J Ethnopharmacol; 72(1–2):323–329. 19. Niu HS, Hsu FL, Liu IM, 2008, Role of sympathetic tone in the loss of syringin-induced plasma glucose lowering action in conscious Wistar rodent. Neurosci Lett; 445(1):113–116. 20. Lohézic-Le Dévéhat F, Bakhtiar A, Bézivin C, Amoros M, Boustie J, 2002, Antiviral and cytotoxic activities of some Indonesian plants. Fitoterapia; 73(5):400–405. 21. Lohézic-Le Dévéhat F, Tomasi S, Fontanel D, Boustie J, 2002a, Flavonols from Scurrula ferruginea Danser (Loranthaceae). Z Naturforsch C; 57(11–12):1092–1095. 22. Ameer OZ, Salman IM, Siddiqui MJA, Yam MF, Sriramaneni RN, Mohamed AJ, Sadikun A, Ismail Z, M. Shah AM, Asmawi MZ, 2010, Pharmacological mechanisms underlying the vascular activities of Loranthus ferrugineus Roxb. in rat thoracic aorta. J Ethnopharmacol; 127(1):19–25. 23. Okpako LC, Ajaiyeoba EO, 2004, In vitro and in vivo antimalarial studies of Striga hermonthica and Tapinanthus sessilifolius extracts. Afr J Med Sci; 33(1):73–75. 24. Xiao YJ, Chen YZ, Chen BH, Chen JH, Lin ZX, Fan YL, 2008, Study on cytotoxic activities on human leukemia cell line HL-60 by flavonoids extracts of Scurrula parasitica from four different host trees. Zhongguo Zhong Yao Za Zhi; 33(4):427–432. 25. Akkol EK, Orhan I, Kartal M, Yeşilada E, 2010, Bioactivity guided evaluation of anti-inflammatory and antinociceptive activities of Arceuthobium oxycedri (D.C.) M. Bieb. J Ethnopharmacol; 128(1):79–84. 26. Fukunaga T, Nishiya K, Kajikawa I, Takeya K, Itokawa H, 1989, Studies on the constituents of Japanese mistletoes from different host trees, and their antimicrobial and hypotensive properties. Chem Pharm Bull (Tokyo); 37(6):1543–1546. 27. Konishi T, Nishio T, Kiyosawa S, Fujiwara Y, Konoshima T, 1996, The constituents of Taxillus kaempferi and the host, Pinus thunbergii. I. Catechins and flavones of Taxillus kaempferi. Yakugaku Zasshi; 116(2):148–157. 28. Khalid SA, Farouk A, Geary TG, James B. Jensen JB, 1986, Potential antimalarial candidates from African plants: An in vitro approach using Plasmodium falciparum. J Ethnopharmacol; 15(2):201–209. 29. Tian Y, Tang H, Wang X, Qiu F, Xue G, Li J, 2009, Studies on antibacterial constituents of Discocleidion rufescens. Zhongguo Zhong Yao Za Zhi; 34(11):1377–1380. 30. Jouad H, Lacaille-Dubois MA, Lyoussi B, Eddouks M, 2001, Effects of the flavonoids extracted from Spergularia purpurea Pers. on arterial blood pressure and renal function in normal and hypertensive rodent. J Ethnopharmacol; 76(2):159–163. 31. Saaby L, Rasmussen HB, Jäger AK, 2009, monoamine oxidase-A inhibitory activity of quercetin from Calluna vulgaris (L.) Hull. J Ethnopharmacol; 121(1):178–181. 32. Patil CR, Jadhav RB, Singh PK, Mundada S, Patil PR, 2010, Protective effect of oleanolic acid on gentamicin-induced nephrotoxicity in rats. Phytother Res; 24(1):33–37. 33. Ge F, Zeng F, Liu S, Guo N, Ye H, Song Y, Fan J, Wu X, Wang X, Deng X, Jin Q, Yu L, 2010, In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis. J Med Microbiol; 59(Pt 5):567–572. 34. Liu J, 1995, Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol; 49(2):57–68. 35. Ibarra A, Feuillere N, Roller M, Lesburgere E, Beracochea D, 2010, Effects of chronic administration of Melissa officinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in rodent. Phytomed; 17(6):397–403.

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36. Kuo YJ, Yang YC, Zhang LJ, Wu MD, Kuo LM, Kuo YC, Hwang SY et al., 2010, Flavanone and diphenylpropane glycosides and glycosidic acyl esters from Viscum articulatum. J Nat Prod; 73(2):109–114. 37. Li Y, Zhao YL, Huang N, Zheng YT, Yang YP, Li XL, 2008, Two new phenolic glycosides from Viscum articulatum. Molecules; 13(10):2500–2508. 38. Yang Y, Un J, Guo K, 2005, Studies on the constituents of Viscum ovalifolium DC. J Guangzhou Univ Trad Chinese Med; 2:144–146. 39. Aragão GF, Cunha Pinheiro MC, Nogueira Bandeira P, Gomes Lemos TL, de Barros Viana GS, 2007, Analgesic and anti-inflammatory activities of the isomeric mixture of alpha- and beta-amyrin from Protium heptaphyllum (Aubl.) March. J Herb Pharmacother; 7(2):31–47.

8

Superorder Caryophyllanae Takht., 1967*

8.1  ORDER CARYOPHYLLALES JUSS. EX BERCHT. & J. PRESL, 1820 The order Caryophyllales consists of 34 families of flowering plants known to produce quinones (naphthoquinone, anthraquinones), flavonoids, and triterpenes that await pharmacological testing for their effects on cancer, bacterial, fungal, viral, parasitic infections, neurodegenerative diseases, inflammation, and skin ageing. Cytotoxic: The naphthoquinone plumbagin isolated from the roots of Plumbago zeylanica L. (family Plumbaginaceae) negated the growth of human B lymphocyte Burkitt’s lymphoma (Raji), human Caucasian lung carcinoma epidermoid grade III (Calu-1), human epithelial cervical cancer (Hela) and human amnion-derived (Wish) cells with IC50 values of 8.1, 25, 21.5, and 21.2 μM, respectively.1 Triterpenoid saponins isolated from the roots of Glinus lotoides L. (family Molluginaceae) abrogated the survival of mouse fibrosarcoma (WEHI164) cells with IC50 values of 0.3 and 0.03 μM, respectively.2 Quercetin-3-O-betaglucuronide isolated from Polygonum amphibium L. (family Polygonaceae) induced apoptosis in human promyelocytic leukemia (HL-60) and Jurkat human T-cell leukemia cultured in vitro with IC50 values of 0.9 and 1.2 μM, respectively.3 The triterpenoid saponin achyranthoside H methyl ester isolated from Achyranthes fauriei H. Lév. & Vaniot (family Amaranthaceae) exhibited significant cytotoxic activities against human breast adenocarcinoma (MCF-7) and human breast carcinoma (MDA-MB-453) cells with IC50 values of 4  and 6.5 μM, respectively, via apoptosis induction.4 The flavonoids 5,4′-O-beta-Ddiglucopyranosylcirsimaritin, cirsimaritin, 4′,5-dihydroxy-7-methoxyflavone, and vomifoliol isolated from Microtea debilis Sw. (family Phytolaccaceae) showed moderate antiproliferative activity against human colon adenocarcinoma (CoLo 205) cells with IC50 values of 7.1, 13.1, 6.1, and 6.8 μM, respectively.5 Antibacterial, antifungal: The triterpene mollugogenol A isolated from Mollugo pentaphylla L. (family Molluginaceae) inhibited the growth of the phytopathogenic fungi Cladosporium cucumerinum at 1.5 μg in vitro.6 The saponin phytolaccoside B isolated from Phytolacca tetramera Hauman (family Phytolaccaceae) inhibited the growth of the dermatophyte fungi Trichophytum mentagrophytes cultured in vitro with a minimum inhibitory concentration of 25 μg/mL.7 The naphthoquinone plumbagin isolated from Plumbago scandens L. (family Caryophyllaceae) inhibited the growth of Gram-positive Staphylococcus aureus and Candida albicans cultured in vitro with minimum inhibitory concentrations of 1.5 and 0.7 μg/mL, respectively.8 The aurone aurantiamide acetate and tiliroside isolated from Gomphrena agrestis Mart. (family Amaranthaceae) exhibited some level of antibiotic activities against Gram-positive Staphylococcus aureus, Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa with minimum inhibitory concentrations of 0.1–0.5 mg/mL.9

*

The superorder Caryophyllanae consists of the single order Caryophyllales.

275

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Medicinal Plants of China, Korea, and Japan

Antiviral: The galloyl-epigallocatechin samaragenin isolated from Limonium sinense (Girard) Kuntze (family Plumbaginaceae) inhibited herpes simplex virus-1 replication in Vero cells with an IC50 value of 11.4 μM.10 The anthraquinone chrysophanol 8-O-beta-d-glucoside isolated from Rheum palmatum L. (family Polygonaceae) exhibited significant activity against hepatitis B virus DNA production with an IC50 value of 36.9 μg/mL.11 Parasiticidal: The monoterpene endoperoxide ascaridole isolated from Chenopodium ambrosioides L. var. antherminticum A. Grey (family Chenopodiaceae) showed potent trypanocidal activity against the epimastigotes of Trypanosoma cruzi, with a minimum lethal concentration of 23 μM.12 The roots of Nepenthes thorelii (family Nepenthaceae) yielded plumbagin and 2-methylnaphthazarin that displayed parasiticidal activity against Plasmodium falciparum with IC50 values of 0.2 and 5.8 μM, respectively.13 A stilbene glycoside isolated from the roots of Pleuropterus ciliinervis Nakai (family Polygonaceae) abrogated the survival of Plasmodium falciparum with an IC50 value of 3.9 μM.14 Polygonum senegalense Meisn. (family Polygonaceae) augments series of chalcones that displayed parasiticidal activity against Plasmodium falciparum with an IC50 value lower than 15 μM.15 Anti-inflammatory: The anthraquinones emodin and rhein isolated from Rheum palmatum L. (family Polygonaceae) significantly inhibited the generation of nitric oxide by murine macrophages (RAW264.7) challenged with lipopolysaccharide with IC50 values of 60.7 and 67.3 μM, respectively.16 Antioxidant: The phenolic alkaloids oleracein A, B, and E isolated from Portulaca oleracea L. (family Portulacaceae) exhibited antioxidant activities in the 2,2-diphenyl-1-picrylhydrazine experiment with IC50 values of 8.9, 5.5, and 9.8 μM, respectively.17 Central nervous system: The cyclic endoperoxide americanoic acid methyl ester isolated from Phytolacca americana L. (family Phytolaccaceae) promoted the growth of neurite of cultured rat cortical neurons at a dose of 1 μM.18 Sceletium tortuosum (L.) N.E. Br. (family Aizoaceae) contains the indole alkaloid mesembrine that inhibits the reuptake of serotonin in the brain.19 Cosmetology: The flavonoid taxifolin isolated from Polygonum hidropiper L. (family Polygonaceae) inhibited the enzymatic of tyrosinase with an IC50 value of 0.5 mM.20 Droseraceae and Caryophyllaceae are among the most interesting families in terms of pharmaceutical discovery in that clade are discussed in detail in this chapter.

8.1.1  Family Caryophyllaceae Juss., 1789, nom. cons., the Pink Family The family Caryophyllaceae is a vast and successful clade consisting of about 75 genera and 2000 species of cosmopolitan herbs that have the ability to accumulate substantial amounts of pentacyclic triterpenoid saponins and unusual series of cyclic peptides. The stems are swollen at the nodes. The leaves are simple, entire, and opposite. The inflorescence is a dichasial cyme. The flowers are hypogynous and pentamerous. The sepals are distinct or connate. The petals are present or absent; if present, the petals are well developed, expanded, with a basal claw and a membranaceous blade. The androecium consists of 5–10 stamens arranged in 1–2 whorls. The anthers are tetrasporangiate and dithecal. The gynoecium consists of 2–5 carpels united to form a compound ovary with distinct styles. The ovary is superior. The fruits are dehiscent papery capsules. The seeds are minute and numerous. The family includes a number of plants grown as garden ornaments, such as Dianthus L. (pink, sweet William) and Gypsophila L. (baby’s breath). The dried roots of Saponaria officinalis L. (Saponaria, Spanish Pharmacopoeia, 1954) has been used as an expectorant and a diuretic, usually as a decoction or an infusion. Saponariae Albae Radix (Hungarian Pharmacopeia, 1954)

277

Superorder Caryophyllanae Takht., 1967

consists of the roots of Gypsophila paniculata L. (Maiden’s breath) that have been used as a decoction or a tincture.

H N

N O

OH N

HO

O

O

NH N H

O

Longicalycin A

A cyclic peptide longicalycin A isolated from Dianthus superbus var. longicalycinus (Maxim.) F.N. Williams abrogated the survival of human hepatocellular liver carcinoma (HepG2) cells cultured in vitro.21 Dianthus superbus L. augments dianthin E and 4-methoxydianthramide B that showed noteworthy cytotoxic activities against human hepatocellular liver carcinoma (HepG2) cells cultured in vitro.22 Arenaria serpyllifolia L. is the first plant discussed in this section. 8.1.1.1  Arenaria serpyllifolia L. [From Latin arena = sand, and serpyllifolia = with leaves like those of thyme] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Thyme leaf sandwort, wu xin cai (Chinese), byeo ruk I ja ri (Korean). Synonyms: Arenaria leptoclados (Rchb.) Guss., Arenaria petiolata Hayata. Habitat: This little annual herb grows in a geographical area covering North America, Eurasia, Africa, and Australia. Diagnosis: The roots of Arenaria serpyllifolia L. are filiform. The stems are erect and hairy. The leaves are sessile. The blade has 3–5 nerves and is lanceolate, 0.2 cm × 0.1 cm to 0.7 cm × 0.5 cm, dull, minutely ciliate, and acute at the apex. The inflorescence is a terminal cyme that is densely flowered. The pedicels are erect, 0.1–1 cm long, and hairy. The sepals have 3 nerves and are green, lanceolate, 0.2 cm long, and acute at the apex. The petals are pure white, oblong, 0.2 cm long, and obtuse at the apex. The capsules are ovoid, 0.3 cm in diameter, and enclosed by the calyx. The seeds are 10–15 in number, black, reniform, and minute (Figure 8.1). Medicinal uses: In China, this plant is used to treat dysentery. In Taiwan, this plant is used to wash the eyes. Pharmacology: Flavonols extracted from Arenaria serpyllifolia L. inhibited the enzymatic activities of intestinal carboxyl esterase.23 The medicinal uses of the plant might be the result of triterpene saponins that are found in the genus Arenaria L.24 Bioresource: Phytochemical and pharmacological investigation. Triterpene saponins abound in Dianthus chinensis L., discussed next.

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Medicinal Plants of China, Korea, and Japan

FIGURE 8.1  Arenaria serpyllifolia L. (From Coll.: E. Rippey. Flora of Western Australia. Loc.: Australia, Stirlings Well (inside fence), Garden Island, 32°11′14″S–115°40′32″E. Date: October 13, 2002.)

8.1.1.2  Dianthus chinensis L. [From Greek dios = divine, and anthos = flower, and from Latin chinensis = from China] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Chinese pink, rainbow pink, shi zhu (Chinese), pae raeng i kkot (Korean), sekitsuku (Japanese). Synonyms: Dianthus amurensis Jacq., Dianthus chinensis var. amurensis (Jacq.) Kitag., Dianthus chinensis var. dentosus (Fisch. ex Rchb.) Debeaux, Dianthus chinensis f. ignescens (Nakai) Kitag., Dianthus chinensis var. ignescens Nakai, Dianthus chinensis var. jingpoensis G.Y. Zhang & X.Y. Yuan, Dianthus chinensis var. liaotungensis Y.C. Chu, Dianthus chinensis var. longisquama Nakai & Kitag., Dianthus chinensis var. macrosepalus Franch. ex L.H. Bailey, Dianthus chinensis var. morii (Nakai) Y.C. Chu, Dianthus chinensis var. subulifolius (Kitag.) Ma, Dianthus chinensis var. sylvaticus W.D.J. Koch, Dianthus chinensis var. trinervis D.Q. Lu, Dianthus chinensis subsp. versicolor (Fisch. ex Link) Ma, Dianthus dentosus Fisch. ex Rchb., Dianthus fischeri Spreng., Dianthus morii Nakai, Dianthus sequieri Chai X, Dianthus sequieri var. dentosus (Fisch. ex Rchb.) Franch., Dianthus subulifolius Kitag., Dianthus versicolor Fisch. ex Link, Dianthus versicolor f. leucopetalus (Kitag.) Y.C. Chu, Dianthus versicolor var. subulifolius (Kitag.) Y.C. Chu. Habitat: It is a perennial herb that grows on sandy soils in a geographical area covering China, Kazakhstan, Korea, Mongolia, Russia, and Europe. It is cultivated as an ornamental plant. Diagnosis: Dianthus chinensis L. is 50 cm tall. The stems are erect and distally branched. The leaves are linear-lanceolate, 3 cm × 0.2 cm to 5 cm × 0.5 cm, narrow at the base, and acuminate at the apex. The flowers are showy, solitary, or several in cymes. The flower pedicel is 1–2.5 cm long. The calyx is cylindrical, 1.5 cm × 0.4 cm to 2.5 cm × 0.5 cm, striate, and develops 5 lobes that are lanceolate, 0.5 cm long, ciliate, and sharply pointed. The petals are bright red, triangular, 1.5 cm long, and irregularly incised at the apex. The  stamens are exerted and the anthers are blue. The ovary is oblong. The styles are linear. The capsules are cylindrical and 4-toothed at the apex. The seeds are black and globose (Figure 8.2).

279

Superorder Caryophyllanae Takht., 1967

FIGURE 8.2  Dianthus chinensis L. (From No. 80. Loc.: Japan, Masuda Machi, Ugo. Date: 1905.)

Medicinal uses: In Korea, this plant is used to treat eczema and skin tumors. It is also used to excite the discharge of urine and for abortions. In Cambodia, Vietnam, Laos, and China, this plant is used to clean the blood, to regulate menses, to check hemorrhages during delivery (probably because of the red color of the flowers), to heal wounds, to treat gonorrhea, and to wash the eyes. In China, this plant affords a diuretic and anti-inflammatory remedy in the treatment of urogenital infection. It is also used to heal carbuncles and to treat cancer of the esophagus. Pharmacology: Dianthus chinensis L. accumulates triterpene saponins that may be responsible for the anti-inflammatory and antiseptic properties of the plant.25 Such saponins could be barbatosides A and B isolated from the aerial parts of Dianthus barbatus L. that

CH3 CH3 H N

HN O N

O

N H

O

O

NH

O O N

Dianthin B

280

Medicinal Plants of China, Korea, and Japan

displayed analgesic and anti-inflammatory activities.26 The diuretic effect of the plant could be mediated by a triterpene or a triterpene saponin as oleanolic acid isolated from Viscum articulatum Burm. f. (order Santalales, family Loranthaceae) protected rodents against gentamicin-induced kidney damage.27 Besides, this plant augments some cyclopeptides such as dianthin A and B that are probably cytotoxic and/or antiviral.28 An ethyl acetate fraction of the plant, with a high phenolic content, displayed dramatic antioxidant and cytotoxic activities against human liver cancer (Bel-7402), human hepatocellular liver carcinoma (HepG2), and human epithelial cervical cancer (Hela) cells cultured in vitro, hence the anticancer use of the plant.29 Bioresource: In vitro pharmacological study of dianthin B for its effect on human immunodeficiency virus infection. The next plant discussed in this section is Drymaria cordata (L.) Willd., Roem., & Schult. 8.1.1.3  Drymaria cordata (L.) Willd., Roem., & Schult. [From Greek drymos = forest, and from Latin cordata = cordate] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Tropical chickweed, he lian dou cao (Chinese). Basionym: Holosteum cordatum L. Synonyms: Drymaria adenophora Urb., Drymaria cordata subsp. diandra (Blume) J.A. Duke, Drymaria cordata var. pacifica Mizush., Drymaria diandra (Sw.) Macfad., Drymaria diandra Blume, Drymaria procumbens Rose, Holosteum diandrum Sw., Stellaria adenophora León. Habitat: It is an obscure annual herb that grows in damp, shaded, grassy sites, often near streams in a geographical area covering China, Taiwan, India, Sri Lanka, Malaysia, Indonesia, Papua New Guinea, and tropical Africa. Diagnosis: Drymaria cordata (L.) Willd., Roem., & Schult. is diffuse, stoloniferous, glabrous, and 30 cm long. The stems are filiform and slender. The leaves are arranged in distant pairs. The blade is membranaceous, irregularly round, cuneate at the base, and 1.5 cm in diameter. The petiole is minute. The inflorescence is a small terminal compound cyme. The bracts are small and ovate. The calyx comprises 5 sepals that are oblong, acute, greenish, and 0.2 cm long. The corolla includes 5 petals that are bifid and white. The capsules are ovoid, trigonous, and have 3 valves (Figure 8.3). Medicinal uses: In Taiwan, a paste of leaves is applied to snakebites. In Indonesia, a paste of leaves is applied to boils and the sap is consumed to relieve the bowels from costiveness and to break fever. In Papua New Guinea, this plant is used to cure fatigue. Pharmacology: The laxative property of Drymaria cordata (L.) Willd., Roem., & Schult. may be the result of anemonin that is acrid.30 Besides, the antiseptic property of this plant is confirmed: different extracts of the plant abrogated the survival of Gram-positive Staphylococcus aureus, Bacillus subtilis, Bacillus pumilis, and Gram-negative Escherichia coli and Pseudomonas aeruginosa cultured in vitro.31 In addition, an extract of the plant exhibited dramatic antitussive activity in rodents exposed to sulfur dioxide.32 Note that an extract of the plant exhibited analgesic activity in the acetic acid-induced abdominal writhing experiment, the hot plate experiment, and the formalin experiment in rodents.33 Furthermore, an extract of Drymaria cordata (L.) Willd., Roem., & Schult. exhibited anxiolytic activity in the hole board, open field, and Morris water maze experiments.34 One might be curious to identify the anxiolytic agent involved here.

Superorder Caryophyllanae Takht., 1967

281

FIGURE 8.3  Drymaria cordata (L.) Willd., Roem., & Schult. (From Coll.: Z. Teruya. Teruya’s Collection. No. 1737. Loc.: Indonesia, Mirabasa, Celebes. Date: 1931.)

Bioresource: Analgesic agent(s). One might consider saponins that abound in the genus Drymaria Willd. ex Schult. and are found in Gypsophila oldhamiana Miq., discussed next. 8.1.1.4  Gypsophila oldhamiana Miq. [From Latin gypsophila = loving gypsum, and after British botanist Richard Oldham (1837–1864), who collected plants in Japan and China for the herbarium of the Royal Botanic Gardens] History: This plant was first formally described in Annales Museum Botanicum LugdunoBatavi by Friedrich Anton Wilhelm Miquel in 1867. Miquel (1811–1871) was a Dutch botanist. Common names: Oldham’s baby’s breath, chang rui shi tou hua (Chinese), dae na mul (Korean). Habitat: It is a perennial herb found in the grasslands of China and Korea. Diagnosis: Gypsophila oldhamiana Miq. is 1 m tall. The root is brownish, thick, and woody. The stems are numerous, dichotomously spreading, and purplish. The leaves are oblong, 4.5 cm × 0.5 cm to 8 cm × 1.5 cm, thick, fleshy, with 3–5 nerves, connate at the base, and apiculate at apex. The inflorescence is a lax corymbose cyme. The bracts are lanceolate, membranaceous, ciliate, and caudate at apex. The pedicel is 0.2–0.5 cm long. The calyx is campanulate and 0.2 cm long. The calyx lobes are ovate, greenish white, membranaceous, ciliate, and acute at apex. The petals are pink, obovate, and 0.5 cm long. The stamens protrude out of the corolla. The styles are exerted, long, and linear. The capsules are ovoid. The seeds are minute, brownish, and reniform (Figure 8.4). Medicinal uses: In China, this plant is used to treat typhoid, rheumatism, lung diseases, and jaundice. Pharmacology: Gypsophila oldhamiana Miq. abounds with triterpene saponins that inhibited the enzymatic activity of alpha-glucosidase, glycogen phosphorylase, and pancreatic lipase.35−38 In addition, this plant augments some cyclopeptides such as gypsophin that

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Medicinal Plants of China, Korea, and Japan

FIGURE 8.4  Gypsophila oldhamiana Miq. (From Coll.: Zimmermann. Ex Museo Botanico Berolinensis. Loc.: China. Date: 1901.)

inhibited the enzymatic activity of alpha-glucosidase.39 The anti-inflammatory component of the plant could be a saponin, as the anti-inflammatory effectiveness of saponins in the carrageenan-induced paw edema experiment is well known.40 Note that glucuronogypsogenin obtained from an unidentified species belonging to the genus Gypsophila L. protected rodents against d-galactosamine, CCl4, and erythromycin-induced liver damage.41 One might be curious to look for antibiotic agents in this plant. Bioresource: In vitro pharmacological study of crude saponin extract as a health supplement for its effect on diabetes and/or obesity. The next plant discussed in this section is Lychnis coronata Thunb. 8.1.1.5  Lychnis coronata Thunb. [From Greek lukhnos = a lamp, and from Latin coronata = crowned] History: This plant was first formally described in Systemat Vegetabilium. Editio Decima Quarta by Carl Peter Thunberg in 1783. Thunberg (1743–1828) was a Swedish botanist. Common names: Chinese lychnis, jian chun luo (Chinese). Synonyms: Agrostemma banksia Meerb., Hedona sinensis Lour., Lychnis grandiflora Jacq., Silene banksia (Meerb.) Mabb., Silene grandiflora Jacq. Habitat: It is a magnificent perennial herb that grows in the grasslands of China and Japan. It is a common ornamental plant. Diagnosis: Lychnis coronata Thunb. is 1 m tall. The root is yellow, fusiform, and fleshy. The stems are solitary. The blade is ovate, 7.5 cm × 1 cm to 15 cm × 2.5 cm, ciliate, cuneate at the base, and acuminate at the apex. The inflorescence is a dichasium that displays numerous showy flowers. The pedicel is minute and hairy. The bracts are lanceolate, herbaceous, and ciliate at the margin. The flowers are 4.5 cm in diameter. The calyx is tubular, glabrous, and 2.5 cm × 0.3 cm to 3.5 cm × 0.5 cm. The petals are pink, obovate, 2.5 cm long, and incised at the apex. The stamens are included. The capsules are elliptical and 2 cm long (Figure 8.5).

283

Superorder Caryophyllanae Takht., 1967

FIGURE 8.5  Lychnis coronata Thunb. (From Leg.: D. Cirtu and G. H. Popoescu. Hortus Botanicus Universitatis Craiovensis, “Flora Olteniae Exsiccata”. Loc.: Romania, Craiova, in silvis inter pagos Radovan et Panaghia. Alt.: 150 m. Date: July 3, 1965.)

Medicinal uses: In China, a paste of leaves and flowers is applied to herpes. In Cambodia, Laos, and Vietnam, this plant is used to treat skin infection and inflammation. Constituents: Members of the genus Lychnis L. are known to augment ecdysteroids.42 Pharmacology: The medicinal properties of the plant might be the result of some ecdysteroids. Note that ergostane-type ecdysteroids obtained from the fungi Polyporus umbellatus (Pers.) Fr. (Basidiomycetes, order Polyporales, family Polyporaceae) exhibited dramatic anti-inflammatory properties against 12-O-tetradecanoylphorbol-13-acetate in rodents.43 In addition, 20-hydroxyecdysone has anti-inflammatory properties similar to cortisone acetate in rodents.44 One might be curious to look for antiviral agents in this plant.

H3C

OH

OH

CH3

HO

CH3

CH3

O CH3

H HO

OH CH3

OH

O

CH3

H

OH H

H

O

O

CH3

O 20-Hydroxyecdysone

H

O Cortisone acetate

Bioresource: In vitro pharmacological study of 20-hydroxyecdysone for its effect on inflammation and/or asthma. Pseudostellaria heterophylla (Miq.) Pax is discussed next.

284

Medicinal Plants of China, Korea, and Japan

8.1.1.6  Pseudostellaria heterophylla (Miq.) Pax [From Greek pseudo = false, and stellaria = the genus stellaria, and from Latin heterophylla = the leaves are different on the same plant] History: This plant was first formally described in Annales Museum Botanicum LugdunoBatavi by Friedrich Anton Wilhelm Miquel in 1867. Miquel (1811–1871) was a Dutch botanist. Common names: False starwort, hai er shen (Chinese). Basionym: Krascheninikovia heterophylla Miq. Synonyms: Krascheninikovia rhaphanorrhiza (Hemsl.) Korsh., Pseudostellaria rhaphanorrhiza (Hemsl.) Pax, Stellaria heterophylla (Miq.) Hemsl., Stellaria. rhaphanorrhiza Hemsl. Habitat: It is a delicate perennial herb found in the forests of Russia, China, and Korea. Diagnosis: The root of Pseudostellaria heterophylla (Miq.) Pax is fibrous. The stems are solitary, erect, and 20 cm tall. The middle leaves are lanceolate and 3 cm × 0.5 cm to 4 cm × 0.8 cm. The distal leaves are decussate, broadly ovate, 3 cm × 1 cm to 6 cm × 2 cm, hairy below, attenuate at the base, and acuminate at the apex. The inflorescence is a cyme. The pedicel is 2 cm long and hairy. The calyx consists of 5 sepals that are lanceolate, 0.5 cm long, hairy below, and ciliate. The corolla comprises 5 petals that are oblong, pure white, and 0.8 cm long. The androecium consists of 10 stamens with purplish anthers. The gynoecium consists of 3 carpels. The capsules are ovoid and have 3 valves. The seeds are brown, minute, reniform, and tuberculate (Figure 8.6). Medicinal use: In China, this plant is used to treat tuberculosis. Constituents: Pseudostellaria heterophylla (Miq.) Pax contains taraxeryl acetate, taraxerol, stigmast-7-en-3beta-ol, beta-sitosterol, daucosterol, stigmast-7-en-3-O-beta-d-glucopyranoside, and dihydroferulic acid as well as ursolic acid and luteolin.45,46

FIGURE 8.6  Pseudostellaria heterophylla (Miq.) Pax.

285

Superorder Caryophyllanae Takht., 1967

Pharmacology: The antitussive property of the plant is confirmed: an extract of roots at a dose of 400 mg/kg reduced the number of coughs in rodents exposed to citric acid.47 Triterpenes probably account for the medicinal property of the plant. Note that the triterpene ursolic acid isolated from a palm tree abrogated the survival of Mycobacterium tuberculosis cultured in vitro.48 Besides, Pseudostellaria heterophylla (Miq.) Pax augments some polysaccharides that are immunostimulating and have antitumor properties.49 The plant produces cyclic peptides known as pseudostellarins that inhibited the enzymatic activity of tyrosinase.50,51 CH3 H3C

CH3

CH3

COOH CH3

HO H3C

CH3 Ursolic acid

Bioresource: In vitro pharmacological studies of pseudostellarin for the whitening of skin and of ursolic acid for tuberculosis. The next medicinal plant discussed in this section is Sagina saginoides (L.) H. Karst. 8.1.1.7  Sagina saginoides (L.) H. Karst. [From Latin sagina = grease, and saginoides = sagina-like] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Arctic pearlwort, wu mao qi gu cao (Chinese). Basionym: Spergula saginoides L. Synonyms: Sagina linnaei Presl, Sagina micrantha (Bunge) Fernald, Sagina saginoides var. hesperia Fernald. Habitat: It is a little perennial herb found in the watery spots and riverbanks of China, Bhutan, India, Japan, Kazakhstan, Korea, Nepal, Pakistan, Russia, Vietnam, South West Asia, Europe, and North America. Diagnosis: The stems of Sagina saginoides (L.) H. Karst. grow in 10-cm-tall clusters. The leaves are linear and 0.5 cm × 0.1 cm to 1.5 cm × 0.1 cm. The flowers are solitary and terminal. The pedicel is 1.5–3 cm long. The calyx comprises 5 sepals that are ovate-oblong, 0.3 cm long, and obtuse at the apex. The corolla comprises 5 petals that are ovate, white, and shorter than the sepals. The androecium comprises 10 stamens. The gynoecium comprises 5 carpels. The fruits are capsular, ovoid, 0.5 cm, shiny, and have 5 valves. The seeds are brown, reniform, and minute. Medicinal uses: In China, this plant is boiled in water and the liquid obtained is drunk to check bleeding. This plant is reduced into a paste that is applied to abscesses.

286

Medicinal Plants of China, Korea, and Japan

Constituents: Two cyclic peptides, sajaponicin C and D, as well as heptadecaene and octadecaene derivatives were isolated from Sagina japonica (Sw.) Ohwi.52,53 Pharmacology: The plant may contain ecdysteroids that may contribute to the healing property mentioned above.42 One might be curious to study the plant for antibacterial properties and/or the styptic effect. Sajaponicins C and D are probably pharmacologically active. Bioresource: Phytochemical and pharmacological investigations and anticancer agent(s). The next plant discussed in this section is Saponaria vaccaria L. 8.1.1.8  Saponaria vaccaria L. [From Latin sapo = soap, and vacca = cow] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common name: Cow cockle. Synonyms: Vaccaria vaccaria (L.) Britton, Vaccaria vaccaria (L.) Huth. Habitat: It is a discrete annual erect herb found in the cultivated fields of Europe, United States of America, Russia, and Northern Asia. It is grown as an ornamental plant. Diagnosis: The stems of Saponaria vaccaria L. are erect, 50 cm tall, and yellowish. The leaves are 2.5 cm × 0.4 cm to 7 × 2 cm, lanceolate, acute at the apex, and sessile. The inflorescence is a spreading panicle with a dichasia of 3–7 flowers. The calyx is 1.5 cm long, cylindrical, contracted below the teeth, and glabrous. The sepals are triangular. The petals are pink and 1.5 cm long. The capsules are 1 cm long, globose, and included in the calyx. The seeds are 0.2 cm in diameter (Figure 8.7).

FIGURE 8.7  Saponaria vaccaria L.

287

Superorder Caryophyllanae Takht., 1967

Medicinal uses: In China, the capsules are used to heal wounds, to check bleeding, and are applied to boils and itches. The plant is also used to treat the lack of milk. Pharmacology: Saponaria vaccaria L. is known to possess antidegranulation and antitumor properties and contains the xanthone sapxanthone, as well as saponins and cyclic peptides.54,55 Saponins probably account for the healing and antiseptic properties mentioned above. OH

H3C

(CH2)4 OH

O

OH

O

(CH2)3

O

O

OCH3

OCH3 Sapxanthone

Bioresource: In vitro pharmacological study of sapxanthone for its effect on neurodegeneration. The next plant discussed in this section is Silene aprica Turcz. 8.1.1.9  Silene aprica Turcz. [From Greek sialon = saliva, and from Latin aprica = sun-loving] History: This plant was first formally described in Index Seminum, quae Hortus Botanicus Imperialis Petropolitanus pro mutua Commutatione offert by Nicolai Stepanovitch Turczaninow in 1835. Turczaninow (1796–1863) was a Russian botanist. Common name: Nu lou cai (Chinese). Synonyms: Elisanthe aprica (Turcz. ex Fisch. & Mey.) Peshkova, Melandrium apricum (Turcz.) Rohrb., Silene aprica var. oldhamiana (Miq.) C.Y. Wu., Silene melandriiformis Maxim., Silene morii Hayata, Silene mushaensis Hayata, Silene oldhamiana Miq., Silene taquetii H. Lév. Habitat: It is a little annual herb found in the mountains of China, Japan, Korea, Mongolia, and Russia. Diagnosis: The stems of Silene aprica Turcz. are erect. The basal leaves are oblanceolate, 4 cm × 0.5 cm to 7 cm × 0.8 cm, attenuate at the base into a long petiole, and acute at the apex. The cauline leaves are lanceolate and smaller than the basal leaves. The inflorescence is a cymule. The pedicel is erect and 2 cm long. The bracts are lanceolate, herbaceous, ciliate, and acuminate at the apex. The calyx is campanulate, 0.8 cm long, and densely hairy. The calyx is marked by greenish longitudinal nerves. The calyx lobes are triangular. The corolla lobes are whitish, lanceolate, and 0.3 cm long. The stamens and styles are included. The filaments are ciliate at the base. The gynoecium consists of 3 hairy carpels. The capsules are ovoid and 1 cm long. The seeds are brownish, reniform, and minute (Figure 8.8). Medicinal uses: In Korea, this plant is used to excite the discharge of urine and to treat breast cancer and diseases of lactation. It is also used to normalize blood circulation and to treat gonorrhea. Pharmacology: Oral administration of an extract of Silene aprica Turcz. protected rodents against CCl4 and acetaminophen-induced hepatocellular damage on probable account of saponins.56 Alpha-spinaterol, ergosterol peroxide, alpha-spinaterol glucoside, and ­ecdysterone

288

Medicinal Plants of China, Korea, and Japan

FIGURE 8.8  Silene aprica Turcz.

isolated from Melandrium firmum Rohrb. inhibited the enzymatic activity of 5-lipoxygenase with IC50 values of 21, 42.3, 32.8, and 17.1 μM, respectively.57 CH3

N CH3

H3C CH3

CH3

CH3 CH3

CH3

O O HO

HO Ergosterol peroxide

Abiraterone

In addition to this, ergosterol peroxide isolated from the plant abrogated the survival of androgen-sensitive human prostate adenocarcinoma (LNCaP) and human prostate carcinoma (DU-145) cells cultured in vitro.58 Bioresource: In vitro pharmacological study of ergosterol peroxide for its effect on prostate cancer. Stellaria media (L.) Vill. is the next medicinal plant discussed in this section.

Superorder Caryophyllanae Takht., 1967

289

8.1.1.10  Stellaria media (L.) Vill. [From Latin stella = star, and media = medium] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Common chickweed, fan lu (Chinese). Basionym: Alsine media L. Synonyms: Stellaria apetala Ucria ex Roem., Stellaria. media var. procera Klatt & Richt. Habitat: This tiny annual herb grows in the fields of Afghanistan, Bhutan, India, Japan, Korea, Pakistan, Russia, and Europe. Diagnosis: The stems of Stellaria media (L.) Vill. are decumbent, angled, and up to 45 cm long. The blade is dull green, somewhat fleshy, lanceolate, and 0.5 cm × 0.2 cm to 4.5 cm × 2 cm. The inflorescence is a terminal cyme. The bracts are ovate, 0.4 cm long, and herbaceous. The pedicels are 0.3 cm long. The flowers are 0.5 cm in diameter. The calyx includes 5 sepals that are lanceolate and 0.5 cm long. The corolla includes 5 petals that are 0.2 cm long, deeply bifid, and pure white. The androecium comprises 3–5 stamens. The anthers are purplish. The gynoecium includes 3 minute styles. The capsules are pinkish, ovoid, 0.5 cm long, and have 6 valves. The seeds are reddish and minute (Figure 8.9). Medicinal uses: In China and Japan, this plant is boiled in water and the liquid obtained is drunk postpartum. This plant is also used to treat the lack of milk and to promote menses and blood circulation. An infusion of this plant is used to check nose bleeding. Pharmacology: The plant contains series of beta-carboline alkaloids including dochotomide III, dochotomide X, and stellarines A and B that inhibited the generation of nitric oxide by murine macrophages (RAW264.7) challenged with lipopolysaccharide with IC50 values of 17.3, 11.3, 19.3, and 18.6 μM, respectively.59

FIGURE 8.9  Stellaria media (L.) Vill. (From Coll.: Kiew R. Brinchang, Flora of Malaya. Forest Research Institute of Malaysia, Kepong, Malaysia. Cameron Highlands, Pahang, Malaysia. RK 5351. Alt.: 3030 m. Date: August 18, 2006.)

290

Medicinal Plants of China, Korea, and Japan OH HO

O

OH

O Apigenin

Apigenin glycosides may account for the hemodynamic effect of Stellaria media (L.) Vill. as apigenin-7-O-beta-d-glucopyranuronide isolated from Salix matsudana Koidz (order Salicales, family Salicaceae) abrogated the production of 12-hydroxy-5,8,10,14-eicosatetraenoic acid.60 Besides, apigenin isolated from Santolina oblongifolia Boiss. (order Asterales, family Asteraceae) inhibited the enzymatic activity of cyclooxygenase and lipoxygenase in vitro and inhibited thromboxane B2 production.61 Stellaria media (L.) Vill. augments some triterpene saponins as well as series of apigenin glycosides.62,63 Bioresource: Phytochemical and pharmacological investigations and hemolytic and/or antiinflammatory agent(s). Another plant used to check bleeding is Stellaria saxatilis Buch.-Ham. ex D. Don, described next. 8.1.1.11  Stellaria saxatilis Buch.-Ham. ex D. Don [From Latin stella = star, and saxatilis = dwelling among rocks] History: This plant was first formally described in Prodromus Florae Nepalensis by David Don in 1825. Don (1799–1841) was a Scottish botanist. Common name: Xi bing fan lu (Chinese). Habitat: It is a perennial herb that is cosmopolitan. Diagnosis: The stems of Stellaria saxatilis Buch.-Ham. ex D. Don are hairy, angular, decumbent, and 25 cm long. The leaves are edible, sessile, narrowly elliptical, 1.5 cm × 0.5 cm to 2.5 cm × 1.3 cm, tapering at the base, and acute at the apex. The inflorescence is a dichotomous cyme. The pedicel is 2.5 cm long, slender, and declinate. The calyx includes 5 sepals that are lanceolate, 0.5 cm long, with 3 nerves, and acute at the apex. The corolla consists of 5 pure white petals that are narrowly linear. The androecium comprises 5 stamens. The filaments are filiform. The gynoecium comprises 3 carpels. The capsules have 3 valves. The seeds are minute and tuberculate (Figure 8.10). Medicinal uses: In China, this plant is boiled in water and the liquid obtained is used to assuage aching bones and to treat cough, hemorrhages, and rheumatism. Pharmacology: Apparently unknown. Stellaria saxatilis Buch.-Ham. ex D. Don probably contains triterpene saponins that may account for the antitussive and anti-inflammatory properties listed above.40 Flavonoids may also play a role in the medicinal use.64 One might be curious to look for analgesics in this plant. Bioresource: Phytochemical and pharmacological investigations and analgesic agent(s). Flavonoids abound in the next clade: the family Droseraceae, discussed in the following section.

291

Superorder Caryophyllanae Takht., 1967

FIGURE 8.10  Stellaria saxatilis Buch.-Ham. ex D. Don.

8.1.2  Family Droseraceae Salisb., 1808, nom. cons., the Sundew Family The family Droseraceae consists of 4 genera and about 100 species of discrete, although odd, carnivorous perennial herbs. The leaves are arranged in rosettes. The blade is covered with sticky glands or produces marginal bristles that entrap insects. Naphthoquinones and flavonoids of pharmacological interest are common in this family. The inflorescence is a cyme. The flowers are small and bisexual. The calyx comprises 4–5 sepals that are imbricate and persistent in fruits. The corolla consists of 5 petals that are hypogynous and free. The anthers are bilocular, extrorse, and open by longitudinal slits. The gynoecium consists of 3–5 carpels united to form a compound and unilocular ovary. The fruits are loculicidal capsules containing innumerable tiny seeds. O CH3

OH OH

O Droserone

Dionaea muscipula J. Ellis (Venus flytrap), a classical example of Droseraceae, has attracted a great deal of interest as a botanical oddity because of its leaves that entrap insects. Drosera rotundifolia L., Drosera anglica Huds. (Drosera longifolia L.), and Drosera intermedia Hayne (sundews, red roots) were traditionally used in Europe to treat spasms, to soothe and to calm cough. The air-dried entire Drosera rotundifolia L. (Drosera, French Pharmacopoeia, 1965) has been used to treat chronic bronchitis, asthma, and whooping cough, usually as tincture (1 in 5; dose 0.5–2 mL).

292

Medicinal Plants of China, Korea, and Japan

Naphthoquinones, including plumbagin and droserone, are acrid and abrogate the survival of a broad spectrum of Gram-positive and Gram-negative bacteria, fungi, and protozoa (Leishmania, Plasmodium). Drosera rotundifolia L. is examined in further detail in this section. 8.1.2.1  Drosera rotundifolia L. [From Greek droseros = dewy, and from Latin rotundifolia = with round leaves] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Round-leaf sundew, yuan ye mao gao cai (Chinese), kkeun kkeun I ju geok (Korean), mosen-goke (Japanese). Synonym: Drosera rotundifolia var. furcata Y.Z. Ruan. Habitat: It is a strange perennial herb found in the wet meadows of China, Japan, Europe, and North America. It is often grown as a botanical oddity. Diagnosis: The root of Drosera rotundifolia L. is fibrous. The stems are 5 cm long. The basal leaves are long petiolate. The stipules are 0.7 cm long, scarious, and closely adnate to the base of the petiole. The petiole is flat and 1–7.5 cm long. The blade is yellowish green, fleshy, orbicular, 0.3 cm × 0.5 cm to 1 cm × 2 cm, with red, long capitate, sticky, glossy, and glandular hairs. The inflorescence is erect, scapiform, slender, 8.5–30 cm long, and densely flowered. The bracts are linear and small. The pedicels are 0.2 cm long. The calyx comprises 5 sepals that are ovate, 0.5 cm × 0.1 cm, glandular, and serrate. The petals are whitish-pink, spatulate, and 0.5 cm × 0.3 cm. The androecium includes 5 stamens that are 0.5 cm long. The ovary is elliptical and 0.3 cm long. The gynoecium consists of 3–4 carpels. The stigma is simple. The capsules have 3 or 4 valves. The seeds are elliptical and minute (Figure 8.11).

FIGURE 8.11  Drosera rotundifolia L. (From No. 85. Loc.: Japan, Ugo. Date: 1905.)

293

Superorder Caryophyllanae Takht., 1967

Medicinal uses: In Japan, this plant is boiled in water and the liquid obtained is drunk to treat cough. Drosera (French Pharmacopoeia, 1965) consists of the air-dried plant. It has been used to treat chronic bronchitis, asthma, and whooping cough, usually as a tincture. Pharmacology: Drosera rotundifolia L. augments the naphthoquinone plumbagone that is antibacterial. Extracts of this plant are antispasmodic and inhibited cholinergic bronchospasms, hence the use of the plant to treat cough. Extracts of the plant inhibited the contraction of guinea pig ileum through a mechanism involving muscarinic receptors probably on account of flavonoids. OH OH

O CH3

O

HO

OH OH

 

O Plumbagone

OH



O Quercetin

Note that extracts of the plant suppressed the activation of activated T lymphocyte membraneinduced inflammatory gene expression in immature human mast (HMC-1) cells.65 Besides, an extract of the plant inhibited the enzymatic activity of human neutrophil elastase, with IC50 values of 5 and 1 μg/mL, respectively, because of the flavonoids hyperoside, quercetin, and isoquercitrin.66 Bioresource: In vitro pharmacological study of quercetin for its effect on skin ageing. The next clade, superorder Asteranae, is discussed in Chapter 9.

REFERENCES

1. Lin LC, Yang LL, Chou CJ, 2003, Cytotoxic naphthoquinones and plumbagic acid glucosides from Plumbago zeylanica. Phytochemistry; 62(4):619–622. 2. Yan MC, Liu Y, Chen H, Ke Y, Xu QC, Cheng MS, 2006, Synthesis and antitumor activity of two natural N-acetylglucosamine-bearing triterpenoid saponins: Lotoidoside D and E. Bioorg Med Chem Lett; 16(16):4200–4204. 3. Smolarz HD, Budzianowski J, Bogucka-Kocka A, Kocki J, Mendyk E, 2008, Flavonoid glucuronides with anti-leukaemic activity from Polygonum amphibium L. Phytochem Anal; 19(6):506–513. 4. Fukumura M, Ando H, Hirai Y, Toriizuka K, Ida Y, Kuchino Y, 2009, Achyranthoside H methyl ester, a novel oleanolic acid saponin derivative from Achyranthes fauriei roots, induces apoptosis in human breast cancer MCF-7 and MDA-MB-453 cells via a caspase activation pathway. J Nat Med; 63(2):181–188. 5. Bai N, He K, Roller M, Lai CS, Shao X, Pan MH, Bily A, Ho CT, 2010, Flavonoid glycosides from Microtea debilis and their cytotoxic and anti-inflammatory effects. Fitoterapia; 82(2):168–172. 6. Hamburger M, Dudan G, Nair AGR, R. Jayaprakasam R, Hostettmann K, 1989, An antifungal triterpenoid from mollugo pentaphylla. Phytochemistry; 28(6):1767–1768. 7. Escalante AM, Santecchia CB, López SN, Gattuso MA, Gutiérrez Ravelo A, Delle Monache F, Gonzalez Sierra M, Zacchino SA, 2002, Isolation of antifungal saponins from Phytolacca tetramera, an Argentinean species in critic risk. J Ethnopharmacol; 82(1):29–34. 8. de Paiva SR, Figueiredo MR, Aragão TV, Kaplan MA, 2003, Antimicrobial activity in vitro of plumbagin isolated from Plumbago species. Mem Inst Oswaldo Cruz; 98(7):959–961. 9. Ferreira EO, Salvador MJ, Pral EM, Alfieri SC, Ito IY, Dias DA, 2004, A new heptasubstituted (E)-aurone glucoside and other aromatic compounds of Gomphrena agrestis with biological activity. Z Naturforsch C; 59(7–8):499–505.

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Medicinal Plants of China, Korea, and Japan

10. Kuo YC, Lin LC, Tsai WJ, Chou CJ, Kung SH, Ho YH, 2002, Samarangenin B from Limonium sinense suppresses herpes simplex virus type 1 replication in Vero cells by regulation of viral macromolecular synthesis. Antimicrob Agents Chemother; 46(9):2854–2864. 11. Li Z, Li LJ, Sun Y, Li J, 2007, Identification of natural compounds with anti-hepatitis B virus activity from Rheum palmatum L. ethanol extract. Chemother; 53(5):320–326. 12. Kiuchi F, Itano Y, Uchiyama N, Honda G, Tsubouchi A, Nakajima-Shimada J, Aoki T, 2002, Monoterpene hydroperoxides with trypanocidal activity from Chenopodium ambrosioides. J Nat Prod; 65(4):509–512. 13. Saxena S, Pant N, Jain DC, Bhakuni RS, 2003, Antimalarial agents from plant sources. Current Science; 85(9):1314–1329. 14. Moon HI, Sim J, 2008, Antimalarial activity in mice of resveratrol derivative from Pleuropterus ciliinervis. Ann Trop Med Parasitol; 102(5):447–450. 15. Bero J, Frédérich M, Quetin-Leclercq J, 2009, Antimalarial compounds isolated from plants used in traditional medicine. J Pharm Pharmacol; 61:1401–1433. 16. Wang CC, Huang YJ, Chen LG, Lee LT, Yang LL, 2002, Inducible nitric oxide synthase inhibitors of Chinese herbs III. Rheum palmatum. Planta Med; 68(10):869–874. 17. Yang Z, Liu C, Xiang L, Zheng Y, 2009, Phenolic alkaloids as a new class of antioxidants in Portulaca oleracea. Phytother Res; 23(7):1032–1035. 18. Takahasi H, Yanagi K, Ueda M, Nakade K, Fukuyama Y, 2003, Structures of 1,4-benzodioxane derivatives from the seeds of Phytolacca americana and their neuritogenic activity in primary cultured rat cortical neurons. Chem Pharm Bull (Tokyo); 51(12):1377–1381. 19. Stafford GI, Pedersen ME, van Staden J, Jäger AK, 2008, Review on plants with CNS-effects used in traditional South African medicine against mental diseases. J Ethnopharmacol; 119(3):513–537. 20. Miyazawa M, Tamura N, 2007, Inhibitory compound of tyrosinase activity from the sprout of Polygonum hydropiper L. (Benitade). Biol Pharm Bull; 30(3):595–597. 21. Hsieh PW, Chang FR, Wu CC, Li CM, Wu KY, Chen SL, Yen HF, Wu YC, 2005, Longicalycin A, a new cytotoxic cyclic peptide from Dianthus superbus var. longicalycinus (MAXIM.) WILL. Chem Pharm Bull (Tokyo); 53(3):336–338. 22. Hsieh PW, Chang FR, Wu CC, Wu KY, Li CM, Chen SL, Wu YC, 2004, New cytotoxic cyclic peptides and dianthramide from Dianthus superbus. J Nat Prod; 67(9):1522–1527. 23. Stocker P, Yousfi M, Djerridane O, Perrier J, Amziani R, El Boustani S, Moulin A, 2004, Effect of flavonoids from various Mediterranean plants on enzymatic activity of intestinal carboxylesterase. Biochimie; 86(12):919–925. 24. Gaidi G, Miyamoto T, Lacaille-Dubois MA, 2001, Junceosides A-C, new triterpene saponins from Arenaria juncea. J Nat Prod; 64(12):1533–1537. 25. Li HY, Koike K, Ohmoto T, 1994, Triterpene saponins from Dianthus chinensis. Phytochemistry; 35(3):751–756. 26. Cordell GA, Lyon RL, Fong HH, Benoit PS, Farnsworth NR, 1977, Biological and phytochemical investigations of Dianthus barbatus cv. “China Doll” (Caryophyllaceae). Lloydia; 40(4):361–363. 27. Patil CR, Jadhav RB, Singh PK, Mundada S, Patil PR, 2010, Protective effect of oleanolic acid on gentamicin-induced nephrotoxicity in rodent. Phytother Res; 24(1):33–37. 28. Wang YC, Tan NH, Zhou J, Wu HM, 1998, Cyclopeptides from Dianthus superbus. Phytochemistry; 49(5):1453–1456. 29. Yu JO, Liao ZX, Lei JC, Hu XM, 2007, Antioxidant and cytotoxic activities of various fractions of extract of Dianthus superbus. Food Chem; 104(3):1215–1219. 30. Hsieh PW, Chang FR, Yen HF, Wu YC, 2003, Anemonin and two norsesquiterpenes from Drymaria diandra. Biochem System Ecol; 31(5):541–543. 31. Mukherjee PK, Bhattacharya S, Saha K, Giri SN, Pal M, Saha BP, 1998, Antibacterial evaluation of Drymaria cordata Willd (Fam. Caryophyllaceae) extract. Phytother Res; 11(3):249–250. 32. Mukherjee PK, Saha K, Bhattacharya S, Giri SN, Pal M, Saha BP, 1997, Studies on antitussive activity of Drymaria cordata Willd. (Caryophyllaceae). J Ethnopharmacol; 56(1):77–80. 33. Barua CC, Roy JD, Buragohain B, Barua AG, Borah P, Lahkar M, 2011, Analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd. Indian J Pharmacol; 43(2):121–125. 34. Barua CC, Roy JD, Buragohain B, Barua AG, Borah P, Lahkar M, 2009, Anxiolytic effect of hydro extract of Drymaria cordata L Willd. Indian J Exp Biol; 47(12):969–973. 35. Liu Z, Li D, Owen NL, Grant DM, Cates RG, Jia Z, 1995, Triterpene saponins from Gypsophila oldhamiana. J Nat Prod; 58(10):1632–1635.

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295

36. Luo JG, Ma L, Kong LY, 2008, New triterpene saponins with dramatic alpha-glucosidase inhibitory activity from the roots of Gypsophila oldhamiana. Bioorg Med Chem; 16(6):2912–2920. 37. Luo JG, Liu J, Kong LY, 2008, New pentacyclic triterpenes from Gypsophila oldhamiana and their biological evaluation as glycogen phosphorylase inhibitors. Chem Biodivers; 5(5):751–757. 38. Zheng Q, Li W, Han L, Koike K, 2007, Pancreatic lipase-inhibiting triterpene saponins from Gypsophila oldhamiana. Chem Pharm Bull (Tokyo); 55(4):646–650. 39. Luo JG, Wang XB, Ma L, Kong LY, 2007, Gypsophin: A novel alpha-glucosidase inhibitory cyclic peptide from the roots of Gypsophila oldhamiana. Bioorg Med Chem Lett; 17(16):4460–4463. 40. Sparg SG, Light ME, Staden J, 2004, Biological activities and distribution of plant saponins. J Ethnopharmacol; 94(2–3):219–243. 41. Braut-Boucher F, Achard-Ellouk S, Pauthe-Dayde D, Henry M, Hoellinger H, 1990, Cytoprotective effects of Gypsophila saponins towards isolated rat hepatocytes. Food Addit Contam; 7(Suppl 1):S127–S130. 42. Zibareva L, Volodin V, Saatov Z, Savchenko T, Whiting P, Lafont R, Dinan L, 2003, Distribution of phytoecdysteroids in the Caryophyllaceae. Phytochemistry; 64(2):499–517. 43. Sun Y, Yasukawa K, 2008, New anti-inflammatory ergostane-type ecdysteroids from the sclerotium of Polyporus umbellatus. Bioorg Med Chem Lett; 18(11):3417–3420. 44. Kurmukov AG, Syrov VN, 1988, Anti-inflammatory properties of ecdysterone. Medicinal’nii Zhurnal Uzbekistana; (10):68–70. 45. Li Y, Yang XW, 2008, Studies on chemical constituents of root tuber of cultivated Pseudostellaria heterophylla (Zheshen No. 1). Zhongguo Zhong Yao Za Zhi; 33(20):2353–2355. 46. Zhang J, Li YB, Wang DW, Yin ZQ, Duan JA, 2007, Chemical constituents from roots Pseudostellaria heterophylla. Zhongguo Zhong Yao Za Zhi; 32(11):1051–1053. 47. Pang W, Lin S, Dai Q, Zhang H, Hu J, 2011, Antitussive activity of Pseudostellaria heterophylla (Miq.) Pax extracts and improvement in lung function via adjustment of multi-cytokine levels. Molecules; 16(4):3360–3370. 48. Jiménez A, Meckes M, Alvarez V, Torres J, Parra R, 2005, Secondary metabolites from Chamaedora tepejilote (Palmae) are active against Mycobacterium tuberculosis. Phytother Res; 19(4):320–322. 49. Wong CK, Leung KN, Fung KP, Choy YM, 1994,The immunostimulating activities of antitumour polysaccharides from Pseudostellaria heterophylla. Immunopharmacol; 28(1):47–54. 50. Morita H, Kayashita T, Takeya K, Itokawa H, 1995, Cyclic peptides from higher plants, Part 15. Pseudostellarin H, a new cyclic octapeptide from Pseudostellaria heterophylla. J Nat Prod; 58(6):943–947. 51. Morita H, Kayashita T, Kobata H, Gonda A, Takeya K, Itokawa H, 1994, Pseudostellarins A–C, new tyrosinase inhibitory cyclic peptides from Pseudostellaria heterophylla. Tetrahedron; 50(23):6797–6804. 52. Jia AQ, Tan NH, Zhou J, 2007, Cyclopeptides from Sagina japonica (Caryophyllaceae). Chem Biodivers; 4(2):241–247. 53. Jia AQ, Yang X, Wang WX, Jia YH, 2010, Glycocerebroside bearing a novel long-chain base from Sagina japonica (Caryophyllaceae). Fitoterapia; 81(6):540–545. 54. Kazmi SN, Ahmed Z, Malik A, 1989, Sapxanthone, a pentasubstituted xanthone from Saponaria vaccaria. Phytochemistry; 28(12):3572–3574. 55. Güçlü-Üstündagˇ O, Balsevich J, Mazza G, 2007, Pressurized low polarity water extract ion of saponins from cow cockle seed. J Food Eng; 80(2):619–630. 56. Ko YJ, Hsieh WT, Wu YW, Lin WC, 2002, Ameliorative effect of Silene aprica on liver injuries induced by carbon tetrachloride and acetaminophen. Am J Chin Med; 30(2–3):235–243. 57. Zheng MS, Hwang NK, Kim do H, Moon TC, Son JK, Chang HW, 2008, Chemical constituents of Melandrium firmum Rohrb. and their anti-inflammatory activity. Arch Pharm Res; 31(3):318–322. 58. Russo A, Cardile V, Piovano M, Caggia S, Espinoza CL, Garbarino JA, 2010, Pro-apoptotic activity of ergosterol peroxide and (22E)-ergosta-7,22-dien-5alpha-hydroxy-3,6-dione in human prostate cancer cells. Chem–Biol Interactions; 184(3):352–358. 59. Chen YF, Kuo PC, Chan HH, Kuo IJ, Lin FW, Su CR, Yang ML, Li DT, Wu TS, 2010, β-Carboline alkaloids from Stellaria dichotoma var. lanceolata and their anti-inflammatory activity. J Nat Prod; 73(12):1993–1998. 60. Zheng YN, Zhang J, Han LK, Sekiya K, Kimura Y, Okuda H, 2005, Effects of compounds in leaves of Salix matsudana on arachidonic acid metabolism. Yakugaku Zasshi; 125(12):1005–1008. 61. Silván AM, Abad MJ, Bermejo P, Villar A, 1998, Effects of compounds extracted from Santolina oblongifolia on T XB(2) release in human platelets. Inflammopharmacol; 6(3):255–263. 62. Hu YM, Wang H, Ye WC, Qian L, 2009, New triterpene from Stellaria media (L.) Cyr. Nat Prod Res; 23(14):1274–1278.

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63. Dong Q, Huang Y, Qiao SY, 2007, Studies on chemical constituents from Stellaria media. Zhongguo Zhong Yao Za Zhi; 32(11):1048–1051. 64. Yang G, Chen D, 2008, Biflavanones, flavonoids, and coumarins from the roots of Stellera chamaejasme and their antiviral effect on hepatitis B virus. Chem Biodivers; 5(7):1419–1424. 65. Fukushima K, Nagai K, Hoshi Y, Masumoto S, Mikami I, Takahashi Y, Oike H, Kobori M, 2009, Drosera rotundifolia and Drosera tokaiensis suppress the activation of HMC-1 human mast cells. J Ethnopharmacol; 125(1):90–96. 66. Krenn L, Beyer G, Pertz HH, Karall E, Kremser M, Galambosi B, Melzig MF, 2004, In vitro antispasmodic and anti-inflammatory effects of Drosera rotundifolia. Arzneimittelforschung; 54(7):402–405.

9

Superorder Asteranae Takht., 1967*

9.1  ORDER ERICALES BERCHT. & J. PRESL, 1820 Members of the order Ericales contain a compelling array of triterpenes (saponins and aglycones), alkylphenols, and naphthoquinones of pharmacological interest in the fields of oncology, bacteriology, mycology, virology, parasitology, diabetology, and cosmetology. Cytotoxic: The phenolics planchols A and B isolated from Actinidia chinensis Planch. (family Actinidiaceae) showed remarkable cytotoxic activities against mouse leukemia (P388) and human lung adenocarcinoma epithelial (A549) cells.1 The lignan egonol isolated from the stems of Styrax camporum Pohl (family Styracaceae) was cytotoxic against mouse glioma (C6) and human laryngeal carcinoma (Hep2) cells with IC50 values of 3.2 and 3.6 μg/mL, respectively.2 The triterpenoid saponin impatienoside G isolated from Impatiens siculifer Hook. f. (family Balsaminaceae) was moderately cytotoxic against human promyelocytic leukemia (HL-60), human stomach adenocarcinoma (KATO-III), and human lung adenocarcinoma epithelial (A549) cells with IC50 values of 21.8, 36.7, and 24.8 μM, respectively.3 The triterpenoid saponin gordonoside isolated from the roots of Gordonia chrysandra Cowan (family Theaceae) abrogated the survival of human intestinal adenocarcinoma (HCT-8), human hepatocellular carcinoma (BEL-7402), human gastric cancer (BGC823), human lung adenocarcinoma epithelial (A549), and human ovarian cancer (A2780) cells with IC50 values of 1.2, 0.7, 2.5, 1.8, and 0.4 μM, respectively.4 An alkyl phenol isolated from Ardisia virens Kurz (family Primulaceae) was toxic for human breast adenocarcinoma (MCF-7), human large-cell lung cancer (NCI-H460), and human glioblastoma (SF268) cells with IC50 values of 3.5, 1, and 2.2 μg/mL, respectively.5 The diterpene secorhodomollolide B isolated from the flower buds of Rhododendron molle (Blume) G. Don (family Ericaceae) showed selective toxicity against human hepatocellular carcinoma (BEL-7402) cells with an IC50 value of 0.9 μM.6 Antibacterial, antifungal: A lignan isolated from the leaves of Styrax ferrugineus Nees & Mart. (family Styracaceae) inhibited the growth of Gram-positive Staphyloccocus aureus and Candida albicans with minimum inhibitory concentrations of 10and 12 μg/ mL, respectively.7 A naphthoquinone isolated from the aerial parts of Impatiens balsamina L. (family Balsaminaceae) displayed antibacterial property against Grampositive Bacillus subtilis with a minimum inhibitory concentration of 8 μg/mL.8 The triterpene aegicerin isolated from the bark of Clavija procera B. Stahl (family Primulaceae) inhibited the growth of Mycobacterium tuberculosis with a minimum inhibitory concentration of 3.1 μg/mL.9 A  triterpene isolated from the leaves of Planchonia careya (F. Muell.) R. Knuth (family Lecythidaceae) inhibited the growth of methicillin-resistant Staphyloccocus aureus, ­vancomycin-resistant, and monkey kidney epithelial (MA104) cells with minimum ­inhibitory concentrations of 0.8 and 0.4 mg/mL, and an IC50 value of 19.2 μg/mL, ­respectively.10 The naphthoquinone diospyrone isolated * The superorder Asteranae is the most recent clade in the evolutionary tree of flowering plants that comprises the orders Cornales, Oncothecales, Metteniusales, Icacinales, Ericales, Euasterids I, and Euasterids II.

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from the stem bark of Diospyros canaliculata De Wild. (family Ebenaceae) displayed antimycobacterial and antigonorrheal activities against Mycobacterium tuberculosis and Gram-negative Neisseria gonorrhoeae with minimum inhibitory concentrations of 2.4 and 1.2 μg/mL, respectively.11 Antiviral: The phenolic ardimerin isolated from Ardisia japonica (Thunb.) Blume (family Primulaceae) inhibited the enzymatic activity of the human immunodeficiency virus-1 and human immunodeficiency virus-2 RNase in vitro with IC50 values of 1.5and 1.1 μM, respectively.12 Parasiticidal: The triterpene saponin arborenin isolated from the leaves of Careya arborea Roxb. (family Lecythidaceae) negated the survival of Leishmania donovanii with an IC50 value of 15 μg/mL.13 An alkylphenol isolated from the leaves of Stylogyne turbacensis (Kunth) Mezz (family Primulaceae) exhibited parasiticidal activities against Trypanosoma cruzi and Leishmania donovanii with IC50 values of 22 and 3 μM, respectively.14 The phenolic 4-O(3′–methylgalloyl)-norbergerin isolated from the stem bark of Diospyros sanza-minika A. Chev. (family Ebenaceae) lysed Plasmodium falciparum with an IC50 value of 0.6 μg/mL.15 Antidiabetic: The triterpene bartogenic acid isolated from the seeds of Barringtonia racemosa Roxb. (family Lecythidaceae) inhibited the enzymatic activity of alpha-glucosidase with an IC50 value of 168 μg/mL.16 Cosmetology: The tannins (−)-epigallocatechin gallate and (−)-epicatechin gallate isolated from Camillia sinensis (L.) Kuntze (family Theaceae) inhibited the enzymatic activity of matrix-metalloproteinase in vitro.17 The order Ericales regroups 22 families of flowering plants of which the Primulaceae is ­discussed here.

9.1.1  Family Primulaceae Batsch ex. Borkh., 1797, nom. cons., the Primrose Family The Primulaceae family consists of about 20 genera and 1000 species of herbs that accumulate substantial amounts of pentacyclic triterpene saponins and alkylphenols. The leaves are simple, alternate, opposite, or whorled, and without stipules. The inflorescence is a panicle, an umbel, or a raceme. The flowers are perfect, hypogynous, regular, and pentamerous. The calyx is tubular and persistent in fruits. The corolla is tubular. The corolla lobes are imbricate. The stamens are as many as and opposite to the petals. The filaments are attached to the corolla tube. The anthers are introrse, tetrasporangiate, dithecal, and open by longitudinal slits. The gynoecium consists of 5 carpels united to form a compound, superior ovary that is unilocular. The fruits are dehiscent capsules. Primulaceae produce pentacyclic triterpene saponins and benzoquinones of pharmacological interest. The dried rhizomes Primula officinalis (L.) Hill (cowslip), Primula elatior (L.) Hill (oxslip), and Primula vulgaris Huds. (primrose) contain high amounts of triterpene saponins and have been used in European medicine to treat cough. The saponin capilliposide B isolated from Lysimachia capillipes Hemsl. was remarkably cytotoxic against human ovarian carcinoma (A-2780) cells cultured in vitro.18 The alkylated benzoquinone primin isolated from Primula obconica Hance ­displayed antimicrobial and cytotoxic properties.19 O H3CO

CH3

O

Primin

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Superorder Asteranae Takht., 1967

O OH CH3

HO O Embelin

The alkylated benzoquinone embelin obtained from Lysimachia punctata L. abrogated the growth of mouse melanoma (B16) cells with an ED50 value of 13 μg/mL.20 The first plant discussed in this section is Androsace umbellata (Lour.) Merr. 9.1.1.1  Androsace umbellata (Lour.) Merr. [From Greek andros = male, and sakos = a shield, and from Latin umbellata = with umbels] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Rock Jasmine, dian di mei (Chinese), bom maj I (Korean). Basionym: Drosera umbellata Lour. Synonyms: Androsace saxifragifolia Bunge, Primula minutiflora Forrest, Primula umbellata (Lour.) Bentv. Habitat: This little herb grows in open grassy areas and on rocks and is found in China, Taiwan, India, Japan, Kashmir, Korea, Burma, Papua New Guinea, Pakistan, the Philippines, Russia, and Vietnam. Diagnosis: The root of Androsace umbellata (Lour.) Merr. is fibrous. The leaves are basal. The petiole is 1–4.5 cm long and hairy. The blade is reniform, 0.5–2 cm wide, hairy, cordate at the base, dentate, and obtuse at the apex. The scapes are numerous, erect, 4.5–15 cm long, and hairy. The inflorescence is an umbel with a few flowers. The calyx is 0.4 cm long, hairy, and persistent in fruits. The calyx lobes are ovate and have 3–6 nerves. The corolla is pure white, 0.5 cm in diameter, and presents a yellowish throat. The corolla tube is 0.2 cm long. The corolla lobes are oblong, valvate, 0.3 cm long, and obtuse at the apex (Figure 9.1). Medicinal uses: In China, this plant is used to treat eye diseases, cough, and uterine disorder and as an antidote to snakebites. It is also used to treat sore throat, detumescence, and cancer. Pharmacology: Androsace umbellata (Lour.) Merr stores a substantial amount of oleanane triterpene saponins that were cytotoxic against human hepatoma cells cultured in vitro.21 One of these is saxifragifolin B that was dramatically cytotoxic against human hepatocellular liver carcinoma (HepG2) cells cultured in vitro achieving an IC50 value of 11.9 μM, via apoptosis induction.22 Besides, oleanane triterpene saponins may be accountable for the bechic and anti-inflammatory properties mentioned above. An extract of Androsace strigillosa Franch. abrogated the survival of the influenza virus cultured in vitro.23

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Medicinal Plants of China, Korea, and Japan

FIGURE 9.1  Androsace umbellata (Lour.) Merr. OHC

HO HO

O

OH OH

O

CH3

HO O

OH

O

O

O

HO

H

CH3 CH3

OH

O H3C

O

O

CH3

CH3

OH

HO OH OH Saxifragifolin B

It would be worth isolating antiviral agents from Androsace umbellata (Lour.) Merr. Triterpene saponins isolated from Androsace septentrionalis L. elicited some levels of estrogenic action and augmented uterine contractile activity.24 Bioresource: In vitro pharmacological study of saxifragifolin B for its effect on liver cancer. The next plant discussed in this section is Lysimachia foenum-graecum Hance.

Superorder Asteranae Takht., 1967

301

9.1.1.2  Lysimachia foenum-graecum Hance [After Lysimachos, a Greek physician of the fourth or fifth century BC, and from Latin foenum = hay and graecus = Grecian] History: This plant was first formally described in Journal of Botany, British and Foreign by Henry Fletcher Hance in 1877. Hance (1827–1886) was a British diplomat. Common names: Circle flower, creeping Jenny, loosestrife, ling xiang cao (Chinese). Habitat: It is a perennial herb found in the wet mixed forests of China. Diagnosis: The herb grows to a height of grows to 60 cm. The stems of Lysimachia foenumgraecum Hance are erect, fleshy and angular. The leaves are alternate. The petiole is ­0.5–1.5 cm long. The blade is broadly ovate, 5 cm × 2 cm to 10 cm × 6 cm, attenuate at the base, and acute at the apex. The blade shows 3–4 pairs of secondary nerves. The flowers are solitary and axillary. The calyx lobes are ovate, 1.2 cm long, and acuminate at the apex. The corolla is yellow, 1.5 cm long, and develops 5 lobes. The filaments are connate at the base forming a ring. The anthers are 0.5 cm long, basifixed, and open by apical pores. The capsules are globose and 0.5 cm in diameter (Figure 9.2). Medicinal uses: In China, this plant is boiled in water and the liquid obtained is gargled to assuage toothache. This plant is also used to clear the nose and to alleviate the feeling of full chest and stomach. Constituents: Lysimachia foenum-graecum Hance abounds with triterpene saponins and kaempferol glycosides.25−27 Pharmacology: An extract of the plant inhibited the differentiation of murine preadipocyte (3T3-L1) cells with an IC50 of 2.5 μg/mL and prevented obesity in rodents on a high-fat diet.28 The anti-inflammatory property of Lysimachia foenum-graecum Hance is confirmed: foenumoside E, an oleanane triterpene isolated from this plant, reduced the secretion of leukotriene B4 from rat peritoneal leukocytes achieving an IC50 value of 74 μM.29 Besides, extracts of the plant showed antioxidant effects in the 2,2-diphenyl-1-picrylhydrazyl experiment.30

FIGURE 9.2  Lysimachia foenum-graecum Hance.

302

Medicinal Plants of China, Korea, and Japan H3C

CH3 R

OH HO HO

CH3

O O

CH3

OH HO

R CH2OGlc

CH3

OH

O

HO O

HO HO

O

H3C

CH3

O H3C HO

O HO

OH Foenumoside

Bioresource: In vitro pharmacological study of foenumoside for its effect on acne. The next plant discussed in this section is Lysimachia japonica Thunb. 9.1.1.3  Lysimachia japonica Thunb. [After Lysimachos, a Greek physician of the fourth or fifth century BC, and from Latin japonica = from Japan] History: This plant was first formally described in Systemat Vegetabilium. Editio Decima Quarta by Carl Peter Thunberg in 1784. Thunberg (1743–1828) was a Swedish botanist. Common names: Japanese yellow loosestrife, xiao jia (Chinese), jom ga ji pul (Korean). Habitat: It is a perennial herb found along grassy banks, ditches, and streams of China, Taiwan, Bhutan, India (specifically Kashmir), Indonesia, Japan, and Korea. It is grown as an ornamental plant. Diagnosis: The stems of Lysimachia japonica Thunb. are prostrate, 25 cm long, and hairy. The leaves are opposite. The petiole is 0.2–0.5 cm long and narrowly winged. The blade is ovate, 1 cm × 0.5 cm to 2.5 cm × 2 cm, hairy, and acuminate at the apex. The blade shows 2–3 pairs of secondary nerves. The flowers are showy, solitary, and axillary. The calyx lobes are lanceolate, 0.3 cm long, hairy, and enlarged in fruits. The corolla is golden yellow, as long as the calyx, and 0.8 cm in diameter. The corolla lobes are broadly lanceolate. The filaments are connate at the base forming a ring. The anthers are ovate, dorsifixed, and minute. The stamens are yellow. The ovary is hairy and the style is 0.3 cm long. The capsules are globose, 0.4 cm in diameter, and hairy at the apex (Figure 9.3). Medicinal uses: In China, the leafy shoots are boiled in water and the liquid obtained is drunk to treat tetanus. In Taiwan, this plant is used to soothe swellings. In the Philippines, this plant is used to treat inflammation of the eyes. OH

HO

CH3 Grevillol

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Superorder Asteranae Takht., 1967

FIGURE 9.3  Lysimachia japonica Thunb. (From W.J.J.O. and B.E.E. de Wilde-Duyfies 13538. Loc.: Indonesia, North Sumatra. Gunung Batu Lopang, c.10 km East South East of Prapat (Lake Toba). Alt.:1400–1500 m. Date: July 8, 1972.)

Pharmacology: Lysimachia japonica Thunb. contains the cytotoxic alkylphenol grevillol that abrogated the survival of human nasopharyngeal carcinoma (KB), murine melanoma (B16F10), embryonal carcinoma (PC13), mouse lymphoma (L-5178Y), mouse leukemia (P388), and human laryngeal carcinoma (Hep2) cells cultured in vitro.31 The antitetanus property of this plant is confirmed as 6-tridecylresorcylic acid isolated from Lysimachia japonica Thunb. inhibited the contraction of myofibrils, precipitation of myosin B, and ATPase activity of myosin.32 OH COOH

HO 6-Tridecylresorcylic acid

CH3

Bioresource: In vitro pharmacological study of grevillol for its effect on brain cancer. The next plant discussed in this section is Lysimachia liui S.S. Chien. 9.1.1.4  Lysimachia liui S.S. Chien [After Lysimachos, a Greek physician of the fourth or fifth century BC, and liui, from Chinese botanist D.J. Liu] History: This plant was first formally described in Contributions from the Biological Labora­ tory of the Science Society of China: Botanical Series by S.S. Chien in 1933. S.S Chien (1883–1965) was a Chinese botanist.

304

Medicinal Plants of China, Korea, and Japan

Common name: Hong tou suo (Chinese). Habitat: It is a perennial herb that grows in the wet areas of China. Diagnosis: Lysimachia liui S.S. Chien is 50 cm tall. The stems are prostrate, branched, and hairy. The leaves are simple and opposite. The petiole is 1.5 cm long. The blade is ovate, 1.5 cm × 1.2 cm to 3.5 cm × 2.5 cm, papery, and round at the base and at the apex. The blade shows 3–4 pairs of secondary nerves. The inflorescence is an axillary umbel of a few flowers. The calyx lobes are lanceolate, 1 cm long, hairy, and acuminate at the apex. The corolla is golden yellow and develops 5 lobes. The corolla tube is 0.3 cm long. The corolla lobes are elliptical, 1 cm × 0.6 cm, red, and obtuse. The filaments are connate at the base forming a tube. The anthers are oblong, 0.2 cm long, and dorsifixed. The ovary is hairy. The style is 0.6 cm long. Medicinal use: In China, this plant is reduced into a paste that is applied to festering wounds. Pharmacology: Apparently unknown. The medicinal uses of Lysimachia liui S.S. Chien could be owed to triterpene saponins that are common in the genus Lysimachia L. and/or alkylphenol derivatives such as embelin. Note that embelin has antibacterial and woundhealing properties.29,33 Embelin isolated from Embelia ribes Burm. f. (family Primulaceae) exhibited healing properties in the excision, incision, and dead space wound experiments in rodents.34 Bioresource: Phytochemical investigation and in vitro pharmacological study of alkylphenols for cosmetics. The next plant discussed in this section is Lysimachia paridiformis Franch. 9.1.1.5  Lysimachia paridiformis Franch. [After Lysimachos, a Greek physician of the fourth or fifth century BC, and from Latin paradisus = paradise, and Latin formis = shape] History: This plant was first formally described in Bulletin Mensuel de la Société Linnéenne de Paris by Adrien René Franchet in 1884. Franchet (1834–1900) was a French botanist. Common name: Luo di mei (Chinese). Habitat: This perennial herb grows in the damp areas in forests of China. It is cultivated as an ornamental plant. Diagnosis: Lysimachia paridiformis Franch. grows to a height of 50 cm tall. The root is fibrous. The stems are erect, swollen at the nodes, and glabrous. The lower leaves are scaly. The upper leaves sessile and arranged into a massive terminal whorl. The blade is elliptical, 5 cm × 1.5 cm to 15 cm × 10 cm, papery, glossy, dotted, dark green, cuneate at the base, acute at the apex, and presents 4–5 pairs of secondary nerves. The umbel is terminal, sessile, and densely flowered. The calyx lobes are lanceolate, glabrous, and acuminate at the apex. The corolla is golden yellow. The corolla tube is 0.3 cm long and produces 5 obtuse lobes that are 1 cm long. The filaments are connate at the base forming a tube. The anthers are elliptical, dorsifixed, and minute. The ovary is glabrous. The gynoecium is 1 cm long (Figure 9.4). Medicinal uses: In China, the flowering parts of this plant are boiled in water and the drink obtained is consumed to treat indigestion and to break fever. This plant is also used to regulate menses. Constituents: The plant produces flavonoids, series of saponins including paridiformoside B, and probably some alkylphenols.35,36 Pharmacology: The gynecological use of Lysimachia paridiformis Franch. might involve some saponins or alkylphenol derivatives as embelin administered to rodents disrupted the estrous cycles and reduced in vitro production of estradiol and progesterone.37

Superorder Asteranae Takht., 1967

305

FIGURE 9.4  Lysimachia paridiformis Franch.

Bioresource: Further pharmacological investigation and estrogenic agent(s). The next plant discussed in this section is Lysimachia phyllocephala Hand.-Mazz. 9.1.1.6  Lysimachia phyllocephala Hand.-Mazz. [After Lysimachos, a Greek physician of the fourth or fifth century BC, and from Latin phyllus = leaves, and Greek kephale = head] History: This plant was first formally described in Notes from the Royal Botanic Garden, Edinburgh by Heinrich Raphael Eduard von Handel-Mazzetti. Handel-Mazzetti (1882– 1940) was an Austrian botanist. Common name: Ye tou guo lu huang (Chinese). Habitat: This perennial herb grows in the forests of China. Diagnosis: Lysimachia phyllocephala Hand.-Mazz. is 30 cm tall. The stems are erect. The leaves are opposite. The petiole is 0.4–1 cm long. The blade is elliptical or lanceolate, 1.5 cm × 0.75 cm to 8 cm × 4 cm, hairy, broadly cuneate at the base, and acute at the apex. The inflorescence is axillary and terminal and displays a few flowers. The calyx lobes are lanceolate, 0.9 cm long, and acuminate at the apex. The corolla is golden yellow and produces 5 lobes. The corolla lobes are membranaceous, oblong, and acute at the apex. The filaments are connate at the base, forming a tube. The anthers are ovate and 0.2 cm long. The style is 0.8 cm long and hairy at the apex. The capsules are globose and 0.4 cm in diameter (Figure 9.5). Medicinal uses: In China, this plant is used to cure atrophied children and to treat eye diseases. Pharmacology: Apparently unknown. The use of the plant to treat eye diseases could be imparted to some anti-inflammatory saponins.29 Note that embelin and 5-O-methylembelin isolated from Embelia schimperi Vatke (family Primulaceae) inhibited the enzymatic activity of hepatitis C virus-protease with IC50 values of 21 and 46 μM, respectively.38 Is embelin active against poliovirus?

306

Medicinal Plants of China, Korea, and Japan

FIGURE 9.5  Lysimachia phyllocephala Hand.-Mazz.

Bioresource: In vitro pharmacological study of embelin for its effect on hepatitis C. The next plant discussed in this section is Primula sieboldii E. Morren. 9.1.1.7  Primula sieboldii E. Morren [From Latin primulus = first, and after Philipp Franz Balthasar von Siebold (1796–1866), a German physician] History: This plant was first formally described in La Belgique Horticole by Charles Jacques Édouard Morren. Morren (1833–1886) was a Belgian botanist. Common names: Japanese woodland primula, Siebold primrose, ying cao (Chinese), sakurasoo (Japanese), aeng cho (Korean). Synonyms: Primula patens Turcz., Primula patens var. genuina Skvortsov, Primula patens var. manshurica Skvortsov, Primula sieboldii f. patens (Turcz.) Kitag. Habitat: This perennial herb grows in wet areas in the forests of China, Japan, Korea, and Russia. This is a common ornamental plant. Diagnosis: The root of Primula sieboldii E. Morren is fibrous. The leaves are arranged in a rosette. The petiole is 3.5–12 cm long and densely hairy. The blade is ovate, 4 cm × 3 cm to 10 cm × 6.5 cm, hairy, cordate at the base, crenate, and round at the apex. The scapes are 10–25 cm tall and hairy. The inflorescence is an umbel of 5–15 flowers. The calyx is campanulate and 0.7 cm long. The calyx lobes are spreading and lanceolate. The corolla is

Superorder Asteranae Takht., 1967

307

FIGURE 9.6  Primula sieboldii E. Morren.

rose-colored. The corolla tube is 1.3 cm long. The corolla lobes are 2 cm wide, ovate, and bifid at the apex. The stamens are attached to the corolla tube. The capsules are globose and seated on the persistent calyx (Figure 9.6). Medicinal use: In China and Japan, the roots are used to treat cough. Pharmacology: Apparently unknown. Series of triterpene saponins are most probably involved in the bechic property of Primula sieboldii E. Morren. One might be curious to study this herb for pharmacology. Bioresource: Phytochemical and pharmacological investigations. Euasterids I are examined in the next section.

9.2  EUASTERIDS I Euasterids I (Lamiids) and the Ericales share an ancestor from which they have inherited the ability to contain naphthoquinones of compelling pharmacological interest. Tannins are uncommon in this clade. In fact, the main active agents reported so far from Euasterids I are quinones (naphthoquinones, anthraquinones, xanthones, and benzoquinones) and diterpenes that await pharmacological testing for their effect on cancer, bacterial infection, malaria, trypanosomiasis, leishamniasis, diabetes, neurodegenerative diseases, inflammation, and skin ageing. Other substances of interest in this clade are steroids, iridoids, and indole alkaloids. Cytotoxic: The indole alkaloid sungucine isolated from the roots of Strychnos icaja Baill. (order Gentianales, family Loganiaceae) was toxic to human leukemic lymphoblast (CCRF-CEM) and human colon adenocarcinoma (CoLo 205) cells with GI50 values of

308

Medicinal Plants of China, Korea, and Japan

0.5 and 5.1 μM, respectively.39 The diterpene scopadiol isolated from the aerial part of Scoparia dulcis L. (order Lamiales, family Plantaginaceae) was cytotoxic against SCL, SCL-6, SCL-37′6, and SCL-9 human stomach adenocarcinoma cells with an IC50 value of 9.7 μM.40 An anthraquinone isolated from the stems of Rubia wallichiana Decne. (order Gentianales, family Rubiaceae) inhibited the growth of human hepatoma (Hepa-3B), human epithelial cervical cancer (Hela), and human colon adenocarcinoma (CoLo 205) cells with IC50 values of 0.6, 9.1, and 0.5 μg/mL, respectively.41 The lignan patentiflorin A isolated from the leaves of Justicia patentiflora Hemsl. (order Lamiales, family Acanthaceae) was remarkably cytotoxic against human nasopharyngeal carcinoma (KB), human colorectal carcinoma (HCT-116), and human breast adenocarcinoma (MCF-7) cells with IC50 values of 0.004, 0.01, 0.003, and 0.04 μMol/L, respectively.42 The quinone rengyolone isolated from Incarvillea delavayi Bureau & Franch. (order Lamiales, family Bignoniaceae) inhibited the growth of human lung adenocarcinoma epithelial (A549), human colorectal carcinoma (Lovo), human promyelocytic leukemia (HL-60), and human hepatocellular liver carcinoma (HepG2) cells with IC50 values of 16.2, 11.6, 5.7, and 20.2 μg/mL, respectively.43 The diterpene icetexane-1 isolated from the stem bark of Premna tomentosa Kurz (order Lamiales, family Lamiaceae) exhibited inhibitory effect against human colon cancer (HT-29), human breast adenocarcinoma (MCF-7), human hepatocellular liver carcinoma (HepG2), and human lung adenocarcinoma epithelial (A549) cells with IC50 values of 16.2, 15.9, 18.6, and 18.6 μg/mL, respectively.44 The indole alkaloid melodine isolated from Melodinus tenuicaudatus Tsiang & P.T. Li (order Gentianales, family Apocynaceae) abrogated the survival of human breast adenocarcinoma (MCF-7), human hepatoma (SMMC-7721), human promyelocytic leukemia (HL60), human colon adenocarcinoma (SW480), and human lung adenocarcinoma epithelial (A549) cells with IC50 values of 2.9, 3.2, 1.1, 1.4, and 4.8 μM, respectively.45 The cardenolide calotoxin isolated from the leaves of Calotropis gigantea (L.) W.T. Aiton (order Gentianales, family Apocynaceae) was toxic to human small-cell lung cancer (NCIH187), human nasopharyngeal carcinoma (KB), and human breast adenocarcinoma (MCF-7) cells with the IC50 values of 0.002, 0.002, and 3.2 μg/mL, respectively.46 A diterpene isolated from the aerial parts of Isodon rubescens (Hemsl.) H. Hara (order Lamiales, family Lamiaceae) was cytotoxic against human promyelocytic leukemia (HL-60), human hepatoma (SMMC-7721), human lung adenocarcinoma epithelial (A549), human breast cancer (SK-BR-3), and human pancreatic carcinoma (PANC-1) cells with IC50 values of 0.9, 4.4, 5.6, 3.3, and 9.8 μM, respectively.47 The sterol withaferin A isolated from the aerial parts of Vassobia breviflora (Sendtn.) Hunz. (order Solanales, family Solanaceae) decreased cell viability of human mouth carcinoma (UM-SCC-2), human squamous carcinoma (MDA1986), and human oral cancer (JMAR) cells with IC50 values of 0.5, 0.8, and 2 μM, respectively.48 The naphthoquinone beta,beta-dimethylacrylalkannin isolated from the roots of Alkanna cappadocica Boiss. & Balansa (order Boraginales, family Boraginaceae) negated the growth of human colon cancer (HT-29), human breast cancer (MDA-MB231), human breast cancer (AU-565), human hepatocellular liver carcinoma (HepG2), human epithelial cervical cancer (Hela), human breast cancer (SK-BR-3), and human osteosarcoma (Saos-2) cells with IC50 values of 0.8, 0.3, 0.6, 1, 0.9, 0.6, and 0.8 μM, respectively.49 Antibacterial, antifungal: The naphthoquinone (S)-alpha-methylbutyryl alkannin isolated from the whole Arnebia euchroma (Royle) I.M. Johnst. (order Boraginales, family Boraginaceae) was bactericidal against Gram-positive Staphylococcus aureus and Enterococcus faecalis with minimum inhibitory concentrations of 0.7 and 1.5 μg/mL, respectively.50 A diterpene isolated from the aerial parts of Calceolaria pinifolia Cav. (order Lamiales, family Calceolariaceae) exhibited antibacterial activity against ­Gram-positive Bacillus subtilis and Staphylococcus aureus with minimum inhibitory

Superorder Asteranae Takht., 1967

309

c­ oncentrations of 8 and 4 μg/mL, respectively.51 The anthraquinone nordamnacanthal ­isolated from Prismatomeris fragrans Geddes (order Gentianales, family Rubiaceae) inhibited the growth of Candida albicans with an IC50 value of 6 μg/mL.52 The anthraquinone zenkequinone B isolated from the stem bark of Stereospermum zenkeri K. Schum. ex De Wild (order Lamiales, family Bignoniaceae) demonstrated antibacterial activity against Gram-negative Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, and Grampositive Bacillus subtilis and Bacillus megaterium with minimum inhibitory concentrations of 37.5, 18.7, 37.5, 37.5, and 37.5 μg/mL, respectively.53 A naphthoquinone isolated from the stems of Avicenna sp. (order Lamiales, family Verbenaceae) showed significant activity against Gram-positive Staphylococcus aureus with a minimum inhibitory concentration of 6.2 μg/mL.54 A diterpene isolated from the aerial parts of Aeollanthus rydingianus Van Jaarsv. & A.E. van Wyk (order Lamiales, family Lamiaceae) showed minimum inhibitory concentrations of 3.9 and 7.8 μg/mL against Gram-positive Staphylococcus aureus and Enterococcus hirae, respectively.55 The benzoquinone globiferin isolated from the roots of Cordia globifera W.W. Sm. (order Boraginales, family Boraginaceae) was antimycobacterial and antimalarial against Mycobacterium tuberculosis and Plasmodium falciparum with a minimum inhibitory concentration of 6.2 μg/mL and an IC50 value of 2.1 μg/mL, respectively.56 Parasiticidal: The anthraquinone sterekunthal A isolated from the root bark of Stereospermum kunthianum Cham. (order Lamiales, family Bignoniaceae) was active against Plasmodium falciparum with an IC50 value of 1.3 μg/mL.57 The lignan bonaspectin C isolated from the aerial parts of Bonamia spectabilis (Choisy) Hallier f. (order Solanales, family Convolvulaceae) displayed an antiplasmodial property against Plasmodium falciparum with an IC50 value of 1.2 μg/mL.58 A diterpene isolated from the fruits of Vitex trifolia L. (order Lamiales, family Lamiaceae) exhibited antiprotozoal activity against Trypanosoma cruzi with a minimum lethal concentration of 11 μM.59 The sterol physangulin C isolated from the aerial parts of Physalis angulata L. (order Solanales, family Solanaceae) showed considerable activity against Trypanosoma cruzi with an IC50 value of 14 μM.60 The indole alkaloid ramiflorine B isolated from the stem bark of Aspidosperma ramiflorum Mull. Arg. (order Gentianales, family Apocynaceae) showed antileishmanial activity against Leishmania amazonensis with an LD50 value of 4.9 μg/mL.61 A sterol isolated from Physalis minima L. (order Solanales, family Solanaceae) was found to have significant antileishmanial activity against Leishmania major with an IC50 value of 0.9 μg/mL.62 The steroidal saponin caratuberside C isolated from Caralluma tuberculata N.E. Br. (order Gentianales, family Apocynaceae) displayed anti-trypanosomal and antimalarial activities against Trypanosoma brucei brucei and Plasmodium falciparum with IC50 values of 1.8 and 3.1 μg/mL, respectively.63 The diterpene 12,16-dideoxy aegyptinone B isolated from Zhumeria majdae Rech. f. & Wendelbo (order Lamiales, family Lamiaceae) showed strong antileishmanial activity against Leishmania donovanii with an IC50 value of 0.7 μg/mL.64 The diterpene gomphostenin A isolated from the leaves of Gomphostemma niveum Hook. f. (order Lamiales, family Lamiaceae) displayed an antiplasmodial property against Plasmodium falciparum with an IC50 value of 3.4 μg/mL.65 Plasmodium ­falciparum growth was inhibited by the sterol tumacone A extracted from the leaves of Solanum nudum Dunal (order Solanales, family Solanaceae) with an IC50 value of 19.5 μM.66 Antiviral: The naphthoquinones rhinacanthin C and D isolated from the leaves and stems of Rhinacanthus nasutus (L.) Kuntze (order Lamiales, family Acanthaceae) exhibited inhibitory activity against cytomegalovirus with EC50 values of 0.02 and 0.2 μg/mL, respectively.67 The flavonoid wogonin obtained from Scutellaria sp. (order Lamiales, family Lamiaceae) protected liver (HepG2.2.15) cells against hepatitis B virus infestation with an IC50 value of 2.6 μg/mL.68

310

Medicinal Plants of China, Korea, and Japan

Central nervous system: The quinone cryptotanshinone isolated from Salvia miltiorrhiza Bunge (order Lamiales, family Lamiaceae) protected cortical neurons against glutamate damage in vitro at doses of 0.1–5 μM.69 The indole alkaloid uleine isolated from Himatanthus lancifolius (Mull. Arg.) Woodson (order Gentianales, family Apocynaceae) inhibited the enzymatic activity of acetylcholinesterase with an IC50 value of 0.4 μM.70 The triterpene alkaloid solasodine isolated from Solanum sisymbriifolium Lam. (order Solanales, family Solanaceae) at a dose of 25 mg/kg protected rodents against pentylenetetrazole-induced convulsions.71 Anti-inflammatory: A naphthoquinone isolated from the stems of Catalpa ovata G. Don (order Lamiales, family Bignoniaceae) inhibited the generation of nitric oxide by murine macrophages (RAW264.7) challenged with lipopolysaccharide with an IC50 value of 2.7 μM.72 Diabetes: The iridoid glucoside catalpol isolated from the roots of Rehmannia glutinosa Gaertn.) Libosch. ex Fisch. & C.A. Mey. (order Lamiales, family Scrophulariaceae) lowered plasma glucose concentrations effectively in streptozocin-diabetic rats at a dose of 0.01–0.1 mg/kg.73 Cosmetology: The phenolic glycoside 6′-O-acetylacteoside isolated from Harpagophytum procumbens (order Lamiales, family Pedaliaceae) inhibited the enzymatic activity of elastase with an IC50 value of 47 μg/mL.74 The phenolic clinopodic acid C isolated from Clinopodium chinense var. parviflorum (Kudô) H. Hara (order Lamiales, family Lamiaceae) inhibited the enzymatic activity of matrix-metalloproteinase with an IC50 value of 3.2 μM.75 An iridoid isolated from Hedyotis diffusa Willd. (order Gentianales, family Rubiaceae) inhibited the enzymatic activity of elastase with an IC50 value of 18 μM.76 The phenolic rosmarinic acid isolated from Meehania fargesii (H. Lev.) C.Y. Wu (order Lamiales, family Lamiaceae) inhibited the enzymatic activity of hyaluronidase.77 The orders Garryales, Gentianales, Lamiales, and Solanales are examined in further detail in this section.

9.2.1  Order Garryales Mart., 1835 The order Garryales consists of two families: the Garryaceae and the Eucommiaceae. 9.2.1.1  Family Eucommiaceae Engl., 1907, nom. cons., the Eucommia Family The family Eucommiaceae consists of the single genus and species Eucommia ulmoides Oliv. native to mountain forests of Western China. 9.2.1.1.1  Eucommia ulmoides Oliv. [From Greek eu = well, and kommi = gum, and from Latin ulmoides = like genus Ulmus] History: This plant was first formally described in Icones Plantarum by Daniel Oliver in 1890. Oliver (1830–1916) was a British botanist. Common names: Eucommia, hardy rubber tree, du zhong (Chinese), tochu cha (Japanese), du chung (Korean). Habitat: It is a deciduous tree that grows in the mountains of China. It is cultivated as a street ornamental plant. Diagnosis: Eucommia ulmoides Oliv. is 25 m tall. The bark is gray-brown and scabrous. The young stems are covered with yellow hairs. The petiole is 1–2.5 cm long and hairy. The blade is pale green, serrate, acuminate, laticiferous, glossy, 5 cm × 2.5 cm to 15 cm × 6.5 cm,

Superorder Asteranae Takht., 1967

311

FIGURE 9.7  Eucommia ulmoides Oliv. (From Leg.: H. Keng. University of Singapore. Loc.: Tree cultivated in Morris Arboretum, Philadelphia, USA. Date: June 7, 1960.)

and displays 5–10 pairs of secondary nerves. The male flowers consist of a single 1-­cm long stamen. The female flowers consist of a 1-cm long ovary. The samaras are 2.5 cm × 1 cm to 3.5 cm × 1.2 cm. The seeds are 1.5 cm long (Figure 9.7). Medicinal uses: In China, the bark is used to cure fatigue, to treat liver, kidney, and spleen diseases, rheumatism, and high blood pressure, and as a sedative. Pharmacology: The plant contains iridoids such as asperuloside which mitigated body weight, white adipose tissue weight, plasma triglyceride levels, and free fatty acids levels in rodents on a high-fat diet.78 Besides, the hypotensive property of the plant is owed to the lignan pinoresinol diglucoside that lowered blood pressure in animals.79 The anxiolytic and invigorating properties may result from the hypotensive effect of the lignan pinoresinol diglucodise. Note that syringaresinol-di-O-beta-d-glucoside, a lignan isolated from Acanthopanax senticosus Harms (order Apiales, family Araliaceae), exhibited a prolonging effect in the forced swimming experiment.80 Note that proanthocyanidin may account for the nephroprotective effect of the plant.81 The plant contains quercetin that inhibited the enzymatic activity of alpha-glucosidase.82 Besides, extracts of leaves showed antioxidant effects, induced apoptosis of human promyelocytic leukemia (HL-60) cells, lowered the glycemia of streptozotocin-induced diabetic rodents, protected rodents against CCl4-induced hepatocellular damage, and induced hypolipidemic effect in hyperlipidemic rodents on a high-fat diet.83−87 An extract of the plant inhibited the replication of the human immunodeficiency virus cultured in vitro.88 Eucommia ulmoides Oliv. contains the iridoid aucubin that is hepatoprotective, antioxidant, inflammatory, antiageing, antiosteoporosis, and neurotrophic.89 Besides, aucubin protected human foreskin fibroblast (HS68) cells against UVB radiation.90 In addition, geniposidic acid and aucubin isolated from the plant stimulated collagen synthesis in rodents.91

312

Medicinal Plants of China, Korea, and Japan OCH3 H3C H3C

H

O

O

H3C

OH O

HO

OH

CH3 CH3

O

H 3C

O

OH

H

O HO

H3CO

OH

OH

OH Pinoresinol diglucoside

OH OH O

H3CO

OH H

HO

O

OH

O

O

OCH3

H

H

H3CO

HO

O

OH HO

O H OCH3

Syringaresinol-di-O-beta-D-glucoside

HO

HO

O HO

O HO

OGlc

O OGlc

HO

Geniposidic acid

Aucubin

Bioresource: In vitro pharmacological study of aucubin for its effect on skin ageing. Iridoids abound in the next clade: the order Gentianales.

9.2.2  Order Gentianales Juss. ex Bercht. & J. Presl, 1820 The order Gentianales consists of five families of flowering plants of which the Gentianaceae is discussed here. 9.2.2.1  Family Gentianaceae Juss., 1789, nom. cons., the Gentian Family The family Gentianaceae consists of about 75 genera and about 1000 species of annual or perennial herbs known to accumulate xanthones and iridoids of pharmacological interest. The largest genus is Gentiana L. that includes about 400 species. The leaves of Gentianaceae are simple, opposite,

313

Superorder Asteranae Takht., 1967

without stipules, and often connate at the base. The flowers are perfect, actinomorphic, showy, and brightly colored. The calyx is tubular or made of free imbricate sepals. The corolla is tubular and presents 5 lobes that are characteristically contorted. The stamens are attached to the corolla tube. The anthers are bilocular and open lengthwise. The gynoecium consists of a pair of carpels united to form a superior and unilocular ovary. The style is simple. The fruits are capsular and contain numerous seeds with copious endosperm. O O

O

H

O

HO O

OH

CH2

OH HO

Gentiopicroside

Sabatia angularis (L.) Pursh (American centaury), Centaurium erythraea Rafn. (European centaury), the dried fermented rhizomes and roots of Gentiana lutea L. (yellow gentian) (Gentian, British Pharmacopoeia, 1963), Gentiana catesbaei Walter, Gentiana macrophylla Pall., Gentiana punctata L., and Gentiana purpurea L. have been used in Western medicine to promote appetite on account of iridoid glucosides that impart to these plants an intense bitterness. The dried flowering tops of the common centaury Centaurium minus Moench. (Centaurium umbellatum Gilib., Erythraea centaurium (L.) Borkh.) and other species of Centaurium Hill (Petite Centaurée, French Pharmacopoeia, 1965) have been used as bitter liquid extracts (1 in 1; dose 2–4 mL) and infusions (1 in 20; dose 30–60 mL). Centaurium beyrichii (Torr. & A. Grey) B.L. Rob. (rock centaury) and Centaurium calycosum (Buckley) Fernald (Buckley centaury) are poisonous to cattle. An interesting pharmacological feature of Gentianaceae is the production of xanthones, namely aglycones and glycosides, the distribution of which is quite restricted to a few families in the Magnoliidae. Xanthones have attracted a great deal of interest because of their ability to inhibit the enzymatic activity of monoamine oxidase. Besides, xanthones are known to inhibit microbial infection, inflammation, cancer cells proliferation, and the aggregation of platelets. The first plant discussed in this section is Canscora diffusa (Vahl) R.Br. ex Roem. & Schult. 9.2.2.1.1  Canscora diffusa (Vahl) R.Br. ex Roem. & Schult. [From Malayalam casjan-cora = Canscora perfoliata Lam, and from Latin diffusa = spreading loosely] History: This plant was first formally described in Symbolae Botanicae by Martin Henrichsen Vahl in 1794. Vahl (1749–1804) was a Danish botanist. Common name: Pu di chuan xin cao (Chinese). Basionym: Gentiana diffusa Vahl. Synonyms: Canscora kirkii N.E. Br., Canscora lawii Wight, Canscora pauciflora Dalzell, Canscora rubiflora X.X. Chen, Canscora tenella Wall., Canscora tenella Wight, Exacum diffusum (Vahl) Willd., Gentiana diffusa Vahl, Orthostemon erectus R.Br., Striga esquirolii H. Lév. Habitat: This annual herb grows in open lands, on rocks, and in grassy spots of China, Bangladesh, Bhutan, India, Indonesia, Laos, Malaysia, Nepal, the Philippines, Sri Lanka, Thailand, Vietnam, tropical Africa, and tropical Australia.

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Medicinal Plants of China, Korea, and Japan

Diagnosis: Canscora diffusa (Vahl) R.Br. ex Roem. & Schult. is 35 cm tall. The stems are slender. The leaves are sessile. The basal leaves are ovate, 1.5 cm × 0.8 cm to 2.4 cm × 1.5 cm, round at the base, and acuminate at the apex. The blade shows 3–5 pairs of secondary nerves. The cyme is lax and spreading. The calyx is 0.5 cm long. The corolla tube is 0.3 cm long. The corolla is salver-shaped. The corolla tube is 1 cm long and develops 3 lobes that are ovate, 0.5 cm long, and purplish. The fertile stamens are shorter than the corolla tube. The capsules are ovoid and 0.5 cm long (Figure 9.8). Medicinal uses: In the Philippines, this plant is boiled in water and the liquid obtained is drunk to cure fatigue and to mitigate stomachache. Pharmacology: Apparently unknown, but one can reasonably frame the hypothesis that the invigorating and gastroanalgesic properties mentioned above involve mangiferin. Mangiferin isolated from Canscora decussata (Roxb.) Roem. & Schult. has been shown to inhibit the enzymatic activity of monoamine oxidase that is a key enzyme in depression.92 OH

HO HO

HO

O

OH

O OH OH

OH Mangiferin

O

Note that an extract of Canscora decussata (Roxb.) Roem. & Schult. exhibited anti-inflammatory property in the carrageenan-induced paw edema experiment on probable account of mangiferin that inhibited tumor necrosis factor-alpha levels in rodents poisoned with bacterial lipopolysaccharides.93,94 In addition, mangiferin significantly abated the formation of gastric insult induced by indomethacin in rodents.95 Moreover, mangiferin isolated from Bombax ceiba L. (order Malvales,

FIGURE 9.8  Canscora diffusa (Vahl) R.Br. ex Roem. & Schult. (From Coll.: Baron Ferd. von Mueller. Phytologic Museum of Melbourne. Loc.: Port Darwin, North Australia.)

Superorder Asteranae Takht., 1967

315

family Bombacaceae) displayed a significant analgesic effect in the acetic acid-induced abdominal writhing experiment and the hot plate experiment in rodents.96 Bioresource: In vitro pharmacological study of mangiferin for its effect on cancer. The next plant discussed in this section is Gentiana chinensis Kusn. 9.2.2.1.2  Gentiana chinensis Kusn. [After Gentius, King of Illyria, who, in the second century BC, found yellow gentian to treat his malaria-stricken army, and from Latin chinensis = from China] History: This plant was first formally described in Bulletin de l’Académie Imperiale des Sciences de St.-Petersbourg by Nicolai Ivanowicz Kusnezow in 1894. Kusnezow (1864– 1932) was a Russian botanist. Common name: Zhong guo long dan (Chinese). Synonym: Gentianodes chinensis (Kusn.) Á. Löve & D. Löve. Habitat: This perennial herb grows in the grasslands and forests of China. Diagnosis: Gentiana chinensis Kusn. is 30 cm long. The stems are papillate. The leaves are opposite. The petiole is 0.3 cm long. The blade is elliptical, 0.5 cm × 0.3 cm to 1.5 cm × 0.7 cm, obtuse, and minutely hairy at margin. The blade shows a single nerve that is conspicuous below. The inflorescence has 1–3 flowers. The calyx tube is 1 cm long and membranaceous. The calyx lobes are linear, 0.2 cm long, unequal, hairy, and acute at the apex. The corolla is blue, conspicuous, tubular, and 3.5 cm long. The corolla lobes are ovate and 0.3 cm long. The stamens are inserted just below the middle of the corolla tube. The filaments are 1 cm long. The anthers are narrowly elliptical and 0.2 cm long. The style is 0.5 cm long. The stigma lobes are linear. The capsules are elliptical and 1.5 cm long. The seeds are light brown, globose, and minute (Figure 9.9).

FIGURE 9.9  Gentiana chinensis Kusn.

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Medicinal Plants of China, Korea, and Japan

Medicinal use: In China, a paste of this plant is applied to dog bites. Pharmacology: Apparently unknown, but one can infer that iridoids and xanthones are involved in the healing property mentioned above. Note that the iridoids sweroside and swertiamarine isolated from Gentiana lutea L. increased the stimulation of collagen synthesis and the mitotic diligence of cultured chicken embryonic fibroblasts.97 In addition, swertiamarine isolated from Enicostemma axillare (Lam.) Raynal. (order Gentianales, family Gentianaceae) exhibited significant analgesic activities in the hot plate experiment and the acetic acid-induced writhing experiment.98 Mangiferin, isogentisin, and gentiopicrin and an extract of Gentiana lutea L. abrogated the survival of a broad spectrum of bacteria with minimum inhibitory concentrations of 0.1–0.3 mg/mL.99 O O

O

OH

H

O

HO O

OH

CH2

OH HO

Swertiamarine

Bioresource: In vitro pharmacological study of swertiamarine for its effect on skin ageing. The next plant discussed in this section is Gentiana loureiroi (G. Don) Griseb. 9.2.2.1.3  Gentiana loureiroi (G. Don) Griseb. [After Gentius, King of Illyria, who, in the second century BC, found yellow gentian to treat his  malaria-stricken army, and João de Loureiro (1717–1791), a Jesuit who traveled in South East Asia] History: This plant was first formally described in A General History of the Dichlamydeous Plants by George Don in 1837. Don (1798–1856) was a Scottish botanist. Common name: Hua nan long dan (Chinese). Basionym: Ericala loureiroi G. Don. Synonym: Gentiana pedicellata var. rosulata Kusn. Habitat: This perennial herb grows in the forests of China, Taiwan, Bhutan, India, Burma, Thailand, and Vietnam. Diagnosis: Gentiana loureiroi (G. Don) Griseb. is 10 cm tall. The root is cylindrical and fleshy. The stems are purple, erect, simple or few-branched, loosely growing in clusters, and densely papillate. The petiole is 0.3–0.7 cm long and hairy. The blade is elliptical, 1.5 cm × 0.3 cm to 3 cm × 0.5 cm, hairy, and obtuse at the apex. The calyx is campanulate and 0.6 cm long. The calyx lobes are erect, lanceolate, 0.4 cm long, membranaceous, hairy, and acute at the apex. The corolla is blue, funnel-shaped, and 1.5 cm long. The corolla lobes are ovate, 0.2 cm long, and obtuse at the apex. The stamens are attached to the middle of the corolla tube. The filaments are 0.6 cm long. The anthers are 0.2 cm long. The style is 0.2 cm long. The stigma lobes are oblong. The capsules are obovoid and 0.5 cm long. The seeds are brown, elliptical, and minute (Figure 9.10). Medicinal uses: In China, this plant is used to cool, to counteract poisoning, and to heal boils, carbuncles, and swellings.

Superorder Asteranae Takht., 1967

317

FIGURE 9.10  Gentiana loureiroi (G. Don) Griseb.

Constituents: Gentiana loureiroi (G. Don) Griseb. accumulates series of iridoid glycosides (including 7-ketologanin, loganin, loganic acid, sweroside, boonein, and isoboonein), flavonoids, and oleanolic acid.100,101 Pharmacology: The anti-inflammatory property of Gentiana loureiroi (G. Don) Griseb. is confirmed: an extract of the plant inhibited the generation of nitric oxide by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides and interferon gamma.102 Note that oleanolic acid may participate in the anti-inflammatory properties of the plant.103 Note that loganin (40 mg/kg, orally administered) significantly improved the scopolamine-induced memory impairment of rodents in the Y-maze test. In addition, loganin (20 and 40 mg/kg, orally administered) improved the performance of rodents poisoned with scopolamine in the passive avoidance test and the Morris water maze test. In addition, loganin significantly inhibited the enzymatic activity of acetylcholinesterase.104 Bioresource: In vitro pharmacological study of loganin for its effect on Alzheimer’s disease. The next plant discussed in this section is Gentiana macrophylla Pall. 9.2.2.1.4  Gentiana macrophylla Pall. [After Gentius, King of Illyria, who, in the second century BC, found yellow gentian to treat his malaria-stricken army, and from Latin macrophylla = large leaves] History: This plant was first formally described in Flora Rossica by Peter Simon Pallas in 1789. Pallas (1741–1811) was a German botanist. Common names: Large leaf gentian, qin jiao (Chinese).

318

Medicinal Plants of China, Korea, and Japan

Habitat: This perennial herb grows in the forests of China, Kazakhstan, Mongolia, and Russia. Diagnosis: Gentiana macrophylla Pall. is 70 cm tall. The root is 25 cm long. The stems are erect and stout. The upper leaves are arranged in pairs. The blade is narrowly elliptical, 5 cm × 2.5 cm to 30 cm × 6 cm, narrowed at the base, scabrous, acute at the apex, and displays 5–7 pairs of secondary nerves. The inflorescence is a terminal cluster that is densely flowered. The flowers are sessile. The calyx tube is membranaceous and develops 4–5 minute lobes. The corolla is tubular and bluish. The corolla lobes are ovate, 0.4 cm long, and obtuse at the apex. The stamens are inserted just below the middle of the corolla tube. The filaments are 0.7 cm long. The anthers are elliptical and 0.2 cm long. The style is 0.1 cm long. The stigma lobes are oblong. The capsules are ovoid and 1.5 cm long. The seeds are light brown, elliptical, and minute (Figure 9.11). Medicinal uses: In China, this plant is used to treat arthritis, convulsions, numbness of the limbs, jaundice, dropsy, tuberculosis, and dysentery. Constituents: Gentiana macrophylla Pall. contains erythrocentauric acid, roburic acid, oleanolic acid, swertiamarine, sweroside, 6′-O-beta-d-glucosylgentiopicroside, gentiopicroside, and gentimacroside.105,106 Pharmacology: The plant is hepatoprotective because it contains gentiopicroside that ­protected rodents against CCl4-induced hepatocellular damage.107

FIGURE 9.11  Gentiana macrophylla Pall.

319

Superorder Asteranae Takht., 1967

O O

CH2 N Gentianine

The anti-inflammatory property of the plant has been validated: an extract of roots lowered the levels of prostaglandin E2 in the inflammatory tissues of rodents as efficiently as prednisone.108 Besides, oral administration of gentianine extracted from Gentiana macrophylla Pall. ­(10–100 mg/kg) lowered the concentration of tumor necrosis factor-alpha and interleukin-6 in the sera of rodents intoxicated with bacterial lipopolysaccharides.109 The antimycobacterial property of the plant may involve xanthones, as a number of xanthones isolated from Canscora decussata (Roxb.) Roem. & Schult. abrogated the survival of Mycobacterium tuberculosis cultured in vitro.110 One might be curious to look for nootropic agents in this plant. Bioresource: Antimycobacterial xanthone(s). The next plant discussed in this section is Gentiana rhodantha Franch. 9.2.2.1.5  Gentiana rhodantha Franch. [After Gentius, King of Illyria, who, in the second century BC, found yellow gentian to treat his malaria-stricken army, and from Greek rhodo = red and anthos = a flower] History: This plant was first formally described in Journal of the Linnean Society, Botany by Adrien René Franchet in 1890. Franchet (1834–1900) was a French botanist. Common name: Hong hua long dan (Chinese). Synonyms: Gentiana jankae Kanitz, Gentiana rhodantha var. wilsonii C. Marquand. Habitat: This perennial herb grows in the grasslands and forests of China. Diagnosis: Gentiana rhodantha Franch. is 50 cm tall. The rhizome is short. The stems are erect. The branches are spreading and glabrous. The petiole is 0.5–1 cm long. The leaves are opposite. The blade is ovate, 2 cm × 0.7 cm to 4.5 cm × 2 cm, serrulate, acute at the apex, round at the base, and shows 3–5 pairs of secondary nerves. The flowers are terminal, solitary, and sessile. The calyx tube is purplish, obconic, 1.3 cm long, membranaceous, and narrowly winged. The calyx lobes are lanceolate and 0.5 cm long. The corolla is bluish, funnel-shaped, 4.5 cm long, and produces 5 lobes. The corolla lobes are ovate, deeply incised, and 0.9 cm long. The stamens are attached to the base of the corolla tube and are unequal. The filaments are 1.2 cm long. The anthers are narrowly elliptical and 0.2 cm long. The style is 0.7 cm long. The stigma lobes are linear. The capsules are elliptical and 2.5 cm long. The seeds are brown, globose, minute, and broadly winged (Figure 9.12). Medicinal uses: In China, this plant is used to break fever and it is prepared into a liquid form drunk to treat gonorrhea. Constituents: Gentiana rhodantha Franch. contains series of iridoid glucosides including  6′-O-beta-glucopyranosyl secologanoside, 6′-O-beta-glucopyranosyl secologanol, 6′-O-beta-d-glucopyranosyl loganic acid, 8-epikingiside, kingiside, secologanoside, secoxyloganin, alpigenoside, rhodanthosides A and B, swertiamarine, and gentiopicroside.111–113

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Medicinal Plants of China, Korea, and Japan

FIGURE 9.12  Gentiana rhodantha Franch. (From Plants of Kweichow Province, China. Loc.: Grassy slope, along roadside. Alt.: 600 m. Collected in cooperation between the Arnold Arboretum of Harvard University, the New York Botanical Garden, and the University of Nanking.)

Pharmacology: Gentiopicroside is an anti-inflammatory agent that has been used for its effect on arthritis, hepatitis, fever, and gastrointestinal diseases and is probably responsible for the antipyretic property of the plant.114 H3C O O

H 2C

CH3

O

OH O

OH HO HO

O

O O

CH2

O HO

O

O HO Rhodanthoside A

OH

O O

HO

OH

HO

Note that gentiopicroside isolated from Gentiana spathacea H.B.K. inhibited the contractions of isolated ileum triggered by histamine, acetylcholine, barium chloride, and potassium chloride.115 One might be curious to test the plant against Gram-negative Neisseria gonorrhoeae.

321

Superorder Asteranae Takht., 1967

Bioresource: In vitro pharmacological study of rhodanthoside A for its effect on skin ageing. The next plant discussed in this section is Gentiana rigescens Franch. 9.2.2.1.6  Gentiana rigescens Franch. [After Gentius, King of Illyria, who, in the second century BC, found yellow gentian to treat his malaria-stricken army, and from Latin rigescens = rather stiff] History: This plant was first formally described in Journal of the Linnean Society, Botany by Adrien René Franchet in 1890. Franchet (1834–1900) was a French botanist. Common names: Dian long dan (Chinese), gwa nam pul (Korean). Synonyms: Gentiana esquirolii H. Lév., Gentiana rigescens var. stictantha C. Marquand, Gentiana rigescens var. violacea Harry Sm. Habitat: This perennial herb grows in the grasslands and forests of China and Burma. Diagnosis: Gentiana rigescens Franch. is 50 cm tall. The root is tuberous and cylindrical. The flowering stems are simple, erect, rigid, woody at the base, and papillate. The leaves are simple, sessile, and opposite. The blade is cuneate, with 1–3 nerves, 1.5 cm × 0.7 cm to 4.5 cm × 2.5 cm, thick, tapering at the base, and obtuse at the apex. The inflorescence is a terminal cluster with 3–10 flowers. The flowers are sessile. The calyx is conical, 1 cm long, and membranaceous. The calyx lobes are unequal. The corolla is violet, bell-shaped, and 2.5 cm long. The corolla lobes are ovate, 0.5 cm long, and acute at the apex. The stamens are attached to the basal part of the corolla tube. The filaments are 1.5 cm. The anthers are narrowly elliptical and 0.2 cm long. The style is 0.2 cm long. The stigma lobes are linear. The capsules are elliptical and 1.2 cm long. The seeds are brown, globose, and minute (Figure 9.13). Medicinal use: In China, this plant is boiled in water and the liquid obtained is drunk to break fever. Pharmacology: Gentiana rigescens Franch. produces some dammarane triterpenes, gentiopicroside, and series of phenolic glycosides that are probably antioxidant.116 Besides, gentiopicroside is a well-known anti-inflammatory iridoid and is probably responsible for the antipyretic property of the plant.114 OH HO

O O

CH3

(CH2)15 CH3

Gentiside A

In addition, this plant contains the alkylphenols gentisides A and B that stimulated the neurite growth of rat pheochromocytoma (PC12) cells cultured in vitro.117 Another neuritogenic phenolic isolated from this plant is gentiside C that stimulated the neurite growth of rat pheochromocytoma (PC12) cells cultured in vitro at 1 μM.118 Bioresource: In vitro pharmacological study of gentiside A or C for its effect on neurodegeneration. The next plant discussed in this section is Gentiana triflora Pall. 9.2.2.1.7  Gentiana triflora Pall. [After Gentius, King of Illyria, who, in the second century BC, found yellow gentian to treat his malaria-stricken army, and from Latin triflora = with 3 flowers] History: This plant was first formally described in Flora Rossica by Peter Simon Pallas in 1789. Pallas (1741–1811) was a German botanist.

322

Medicinal Plants of China, Korea, and Japan

FIGURE 9.13  Gentiana rigescens Franch.

Common names: Clustered gentian, Korean Gentian, san hua long dan (Chinese), ezorindou (Japanese), gwa nam pul (Korean). Habitat: This perennial herb grows in the forests of China, Japan, Korea, Mongolia, and Russia. Diagnosis: The stems of Gentiana triflora Pall. are straight and glabrous. The leaves are simple and opposite. The blade is 5 cm × 0.3 cm to 10 cm × 0.9 cm and narrowly elliptical. The inflorescence is an axillary cluster. The bracts are 1 cm long. The flowers are sessile. The calyx tube is 1.2 cm long and split on one side. The calyx lobes are triangular, 0.8 cm long, and acute at the apex. The corolla is purplish, campanulate, and 4.5 cm long. The corolla lobes are orbicular, 0.7 cm long, and obtuse at the apex. The stamens are attached to the middle of the corolla tube. The filaments are subulate and 1 cm long. The anthers are elliptical and 0.4 cm long. The style is 0.2 cm long. The capsules are 1.5 cm long and the seeds are 0.2 cm long (Figure 9.14). Medicinal uses: In China, the roots are used to break fever and to treat jaundice, liver diseases, inflammation of the eyes, sore throat, fatigue, cancer, and ulcers. Pharmacology: The anticancer property of Gentiana triflora Pall. is validated: an extract of roots abrogated the survival of human Burkitt’s lymphoma (Daudi) cells cultured in vitro.119 H3CO

O

OH OH O OH Gentiakochianin

Superorder Asteranae Takht., 1967

323

FIGURE 9.14  Gentiana triflora Pall. (From Coll.: N. Naruhashi. Plantae Japonicae Exsiccatae. Ex Herbario Universitatis Kyotoensis. No. 1142. Loc.: Japan, Hokkaido, Nemuro, en route from Habomai to Tomochi (Gorufujombe), Nemuro Peninsula. Among herbs on open moist meadow. Date: September 8, 1965.)

The active agent involved here remains unidentified, but one could reasonably think of xanthones as gentiakochianin and gentiacaulein isolated from Gentiana kochiana Perr. & Songeon abrogated the survival of both mouse glioma (C6) and human glioblastoma (U251) cells cultured in vitro.120 Besides, Gentiana triflora Pall. contains gentiopicroside that is known to be hepatoprotective and anti-inflammatory.107,114,121 Bioresource: In vitro pharmacological study of gentiakochianin for its effect on brain cancer. The next plant discussed in this section is Menyanthes trifoliata L. 9.2.2.1.8  Menyanthes trifoliata L. [From Greek menyein = disclosing, and anthos = flower, and from Latin trifoliata = with 3 leaves] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Bogbean, buckbean, marsh trefoil, shi cai (Chinese). Habitat: This perennial aquatic herb of fine form grows in swamps, bogs, fens, and mud and is found in China, Japan, Kashmir, Mongolia, Nepal, Russia, North Africa, North America, Southwest Asia, and Europe. The plant is ornamental. Diagnosis: The rhizome of Menyanthes trifoliata L. is creeping and sympodial. The petiole is erect and 10–20 cm long. The leaves are trifoliate. The leaflets are 2.5–4.5 cm long and obovate. The inflorescence is a raceme. The calyx is 0.5 cm long. The corolla lobes are ovate and obtuse at the apex. The corolla is pure white, star-shaped, tubular, 1.7 cm long,

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Medicinal Plants of China, Korea, and Japan

FIGURE 9.15  Menyanthes trifoliata L.

and hairy on the inside. The corolla lobes are elliptical, 1 cm long, and obtuse at the apex. The filaments are linear and 0.6 cm long. The anthers are sagittate and 0.2 cm long. The styles are linear and 1.2 cm long. The stigma lobes are oblong. The capsules are globose and 0.6 cm in diameter. The seeds are orbicular, 0.2 cm long, and smooth (Figure 9.15). Medicinal uses: In Japan, this plant is used as bitter to promote appetite. In China, the leaves are used as a sedative. Constituents: Menyanthes trifoliata L. is known to contain trifolioside, trifolin, dihydrofoliamenthin, menthiafolin, and loganin as well as triterpene saponins.122−124 Pharmacology: Loganin displayed antiamnesic activity in the Morris water maze experiment and inhibited the enzymatic activity of acetylcholinesterase in rodents.104 In addition, an extract of the plant showed significant antitumor properties and some polysaccharide fraction of the plant showed immunomodulating effects.125,126 One might be curious to look for hypnotic and cytotoxic agents in the plant.

O

H3CO

O O

H

H

OH

HO

CH3 OH Loganin

O HO

OH

Superorder Asteranae Takht., 1967

325

Bioresource: In vitro pharmacological study of loganin for its effect on Alzheimer’s disease. The next plant discussed in this section is Nymphoides peltata (S.G. Gmel.) Kuntze. 9.2.2.1.9  Nymphoides peltata (S.G. Gmel.) Kuntze [From Latin nymphoides = like genus Nymphaea, and peltata = shield-shaped] History: This plant was first formally described in Novi Commentarii Academiae Scientiarum Imperalis Petropolitanae by Samuel Gottlieb Gmelin in 1769. Gmelin (1744–1774) was a German botanist. Common names: Fringed Waterlily, yellow floating-heart, water fringe, xing cai (Chinese), asaza (Japanese). Basionym: Limnanthemum peltatum S.G. Gmel. Habitat: It is a perennial aquatic herb that grows in ponds, lakes, and slow-moving rivers and is found in China, Japan, Korea, Mongolia, Russia, Southwest Asia, and Europe. It is also grown as an ornamental plant. Diagnosis: The stems of Nymphoides peltata (S.G. Gmel.) Kuntze are cylindrical. The leaves are alternate at the base of stems and are opposite at the apex. The petiole is cylindrical, 5–10 cm long, and the base enlarged into an amplexicaul sheath. The blade is peltate orbicular, 1.5–8.5 cm in diameter, thick, purplish beneath, cordate at the base, and without distinct nervations. The flowers are showy and arranged in clusters at nodes. The calyx is 0.9 cm long. The calyx lobes are elliptical and obtuse at the apex. The corolla is yellow, 3 cm long, and rotates. The corolla lobes are obovate and round at the apex. The filaments are hairy and 0.4 cm long. The style is 0.2 cm long. The anthers are curved, sagittate, and 0.6 cm long. The ovary is 1.5 cm long. The style is 1 cm long. The stigma is large, bilobed, and orbicular. The capsules are elliptical and 2.5 cm × 1 cm. The seeds are brown, compressed, elliptical, 0.4 cm long, and densely ciliate (Figure 9.16).

FIGURE 9.16  Nymphoides peltata (S.G. Gmel.) Kuntze.

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Medicinal Plants of China, Korea, and Japan

Medicinal uses: In China, this plant is used to break fever and a paste of leaves is applied to swellings, burns, ulcers, and snakebites. This plant is also used to excite the discharge of urine. In Cambodia, Laos, and Vietnam, this plant is used to cure fatigue and to heal furuncles and sprain. Pharmacology: The pharmacological property of Nymphoides peltata (S.G. Gmel.) Kuntze and of the whole genus Nymphoides Ség. remains insufficiently explored. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory agent(s). The next plant discussed in this section is Swertia punicea Hemsl. 9.2.2.1.10  Swertia punicea Hemsl. [After Emanual Sweert, sixteenth-century Dutch botanist, and from Latin punicea = reddish-purple] History: This plant was first formally described in Journal of the Linnean Society, Botany by William Botting Hemsley in 1890. Hemsley (1843–1924) was a British botanist. Common name: Zi hong zhang ya cai (Chinese). Habitat: It is an annual herb that grows in the grasslands, on the riverbanks, and in the forests of China. Diagnosis: The root of Swertia punicea Hemsl. is yellow and stout. The stems are erect, 0.7 cm in diameter, 80 cm long, quadrangular, and densely branched. The leaves are sessile, lanceolate, 6.5 cm × 1.8 cm, acuminate at the apex, and prominently nerved. The inflorescence is a densely flowered panicle of cymes. The calyx tube is 0.1 cm long. The calyx lobes are lanceolate, 0.7 cm long, and acuminate at the apex. The corolla is purplish and 1 cm in diameter. The corolla tube is 0.1 cm long and develops 5 lobes that are lanceolate, 1 cm long, and acuminate at the apex. The filaments are 0.6 cm long. The anthers are elliptical and 0.2 cm long. The style is indistinct. The stigma lobes are capitate. The capsules are elliptical and 1.2–1.5 cm long. The seeds are yellow, elliptical, minute, and warty. Medicinal use: In China, this plant is used to treat hepatitis. Constituents: This plant contains gentiopicroside, mangiferin, swertrianolin, swertia­ punimarin, sweroside, swertiamarine, oleanolic acid, daucosterol, beta-sitosterol, and methylswertianin.127,128 Pharmacology: Methylswertianin and bellidifolin isolated from Swertia punicea Hemsl. significantly lowered the glycemia of streptozotocin-induced diabetic rodents.129 Gentiopicroside has been used to treat hepatitis in China and may account, with oleanolic acid, for the medicinal use of the plant.114 Besides, 3-O-demethylswertipunicoside extracted protected rat pheochromocytoma (PC12) cells against 1-methyl-4-phenylpyridinium ion, rotenone, or H2O2-induced cellular damage.130 H3CO

O

OCH3 OH O OH Methylswertianin

Bioresource: In vitro pharmacological study of methylswertianin for its effect on diabetes. Iridoids are probably present in Swertia punicea Hemsl. and are also present in the next clade: the order Lamiales.

327

Superorder Asteranae Takht., 1967

9.2.3  Order Lamiales Bromhead, 1838 The order Lamiales consists of 24 families of which the Oleaceae and the Orobanchaceae are discussed here. 9.2.3.1  Family Oleaceae Hoffmanns. & Link, 1809, nom. cons., the Olive Family The family Oleaceae consists of some 30 genera and 600 species of flowering plants best developed in Asia and Malesia. These are trees, shrubs, or climbers commonly producing iridoids and phenolic glycosides. The leaves are opposite, simple, or pinnate and without stipules. The inflorescence is a cyme. The flowers are small and perfect. The calyx has 4 lobes. The calyx lobes are valvate. The corolla is tubular and has 4 lobes. The corolla lobes are imbricate. The androecium consists of a pair of stamens attached to the corolla tube. The anthers are dithecal and open by longitudinal slits. The gynoecium consists of a pair of carpels united to form a compound, superior, bilocular ovary with a terminal style and a bilobed stigma. The fruits are loculicidal or circumscissile capsules or samaras, berries, or drupes. A classical example of Oleaceae is Olea europea L. Olive Oil (British Pharmacopoeia, 1963) consists of the fixed oil extracted from the ripe fruits of Olea europea L. Olive oil is nourishing, soothing, and loosens the bowels when consumed. It softens the skin and soothes inflamed parts when used externally, and has been used to soften the skin and crusts in eczema and psoriasis. It has also been used to heal burns. It is used in the preparation of liniments, ointments, plasters, and soaps. Manna (British Pharmaceutical Codex, 1934) is the dried saccharine juice exuded from the stems of Fraxinus ornus L., usually containing 40–60% mannitol. Manna has been used as a mild laxative for infants and children. Fraxinus (French Pharmacopoeia, 1965) consists of the leaves of Fraxinus excelsior L. (European ash). The leaves are bitter, astringent, and have been claimed to have diuretic and laxative properties and produce perspiration. H3C

CH3

CH3 H

HO H3C

H

CH3

OH

CH3

H CH3 Erythrodiol

Triterpenes, flavonoids, and phenolic glycosides of pharmacological interest have been obtained so far from the family Oleaceae. The triterpene erythrodiol extracted from Olea europea L. ­exhibited a ­cytotoxic activity against human colon cancer (HT-29) cells cultured in vitro with an EC50 value of 48.8 μM.131 The flavonoids kaempferol, luteolin, quercetin, and apigenin isolated from Chionanthus retusus Lindl. & Paxton showed antiproliferative effects against human lung ­adenocarcinoma epithelial (A549), human ovary adenocarcinoma (SK-OV-3), human skin melanoma (SK-MEL-2), and human colorectal ­adenocarcinoma (HCT-15) cells cultured in vitro.132 A phenolic glycoside isolated from Syringa velutina Kom was remarkably cytotoxic against mouse leukemia (P-388), mouse lymphocytic leukemia (L-1210), human gastric carcinoma (SNU-5), and human promyelocytic leukemia (HL-60) cells cultured in vitro.133 The first plant examined in this section is Forsythia suspensa (Thunb.) Vahl.

328

Medicinal Plants of China, Korea, and Japan

9.2.3.1.1  Forsythia suspensa (Thunb.) Vahl [After William Forsyth (1737–1804), who, in 1804, was one of the founders of the Horticultural Society of London, and from Latin suspensum = to hang] History: This plant was first formally described in Nova Acta Regiae Societatis Scientiarum Upsaliensis by Carl Peter Thunberg in 1780. Thunberg (1743–1828) was a Swedish botanist. Common names: Weeping Forsythia, weeping golden bells, lian qiao (Chinese), dang gae na ri (Korean). Basionym: Ligustrum suspensum Thunb. Synonyms: Forsythia fortunei Lindl., Forsythia suspensa var. fortunei (Lindl.) Rehder, Forsythia suspensa var. latifolia Rehder, Forsythia suspensa f. pubescens Rehder, Forsythia suspensa var. sieboldii Zabel, Rangium suspensum (Thunb.) Ohwi, Syringa suspensa (Thunb.) Thunb. ex Murray. Habitat: This perennial shrub is native to China. It is a common garden ornamental plant and bonsai. Diagnosis: The stems of Forsythia suspensa (Thunb.) Vahl are pendulous. The leaves are simple. The petiole is 0.5–1.5 cm long. The blade is lanceolate, 2 cm × 1.5 cm to 10 cm × 5 cm, papery, round at the base, serrate, and acute at the apex. The flowers are axillary. The calyx lobes are oblong, 0.6 cm long, and ciliate. The corolla lobes are oblong, 2 cm long, and yellow. The stamens are 0.4 cm long. The gynoecium is 0.6 cm long. The capsules are ovoid, 2.5 cm × 1.2 cm, and lenticelled (Figure 9.17). Medicinal uses: In China, this plant is used as a sedative and as a laxative, to excite the discharge of urine, to induce menses, to expel worms from the intestines, to break fever, and to remove ringworm. This plant is also used to heal ulcers, hemorrhoids, and abscesses and to remove malignant tumors. Besides, the plant is used to stop vomiting, to dissolve blood clots, to treat cancer of the breast, jaundice, and cancerous sores. In Cambodia, Laos, and Vietnam, this plant is used to break fever. Pharmacology: The anti-inflammatory property of the plant is confirmed: an extract of Forsythia suspensa (Thunb.) Vahl inhibited the multiplication of lymphocytes stimulated with concanavalin A and inhibited the secretion of nitric oxide by macrophages.134,135 OH CH3

HO O

HO O

O O HO

O

O

OH

OH

HO

OH

OH Forsythiaside

Besides, an extract of the plant protected piglets against beta-conglycin-induced anaphylactic reaction on probable account of dammarane triterpenes.136−138

329

Superorder Asteranae Takht., 1967

FIGURE 9.17  Forsythia suspensa (Thunb.) Vahl. (From Leg.: H. Keng. University of Singapore. Loc.: Shrub cultivated in Morris Arboretum, Philadelphia, USA. Date: June 7, 1960.) OH O

H3C N

O H

O

O

HO

O

H

HO O 2-(1,4-dihydroxycyclohexanyl)-acetic acid

O



Bicuculline



OCH3 O HO

OH

H

H

HO O

OCH3 Forsythialan A

In addition, an extract of Forsythia suspensa (Thunb.) Vahl showed remarkable antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl experiment on probable account of the phenolic glycoside forsythiaside that exhibited dramatic antioxidant and antibacterial activities.139,140 Besides, forsythiaside induced the vasodilation of norepinephrine-induced preconstricted rat aorta.141 Other anti-inflammatory agents isolated from this plant are suspensine A and 7′-O-methylegenine, egenine, and bicuculline that inhibited the secretion of beta-glucuronidase from murine polymorphonuclear leukocytes.142

330

Medicinal Plants of China, Korea, and Japan

Moreover, an extract of the plant protected rodents against diquat-induced oxidative damage.139 Some lignans isolated from the fruits abrogated the copper-induced lipid peroxidation of human high-density lipoprotein.143 The lignans phillygenin, 8-hydroxypinoresinol, forsythialan A, and forsythialan B protected porcine kidney (LLC-PK1) cells against 3-morpholinosydnonimine-induced cellular damage.144,145 An extract of the plant abrogated the replication of the respiratory syncytial virus cultured in vitro on probable account of 2-(1,4-dihydroxycyclohexanyl)-acetic acid and/or forsythoside A.146 Note that the phenolic forsythoside A protected primary chicken embryo kidney cells against avian infectious bronchitis virus infestation.147 Bioresource: In vitro pharmacological study of 2-(1,4-dihydroxycyclohexanyl)-acetic acid and forsythoside A for their effect on respiratory syncytial virus infection. The next plant discussed in this section is Fraxinus chinensis Roxb. 9.2.3.1.2  Fraxinus chinensis Roxb. [From Latin Fraxinus = a classical Latin name for this genus, and from chinensis = from China] History: This plant was first formally described in Flora Indica; or Descriptions of Indian Plants by William Roxburgh in 1820. Roxburgh (1751–1815) was a Scottish botanist. Common names: Chinese ash, bai la shu (Chinese), mul pu re na mu (Korean). Synonyms: Fraxinus japonica Blume ex K. Koch, Fraxinus rhynchophylla Hance. Habitat: This tree grows along the riverbanks of China, Japan, Korea, Russia, and Vietnam. The plant is ornamental and can be made into bonsais. The wood has commercial value. Diagnosis: Fraxinus chinensis Roxb. is 25 m tall. The leaves are compound and 10–35 cm long. The petiole is 3–10 cm long. The rachis is hairy and supports 3–7 leaflets. The petiolule is 0.2–1.5 cm long. The leaflets are lanceolate, 4 cm × 2 cm to 15 cm × 7 cm, papery, blunt at the base, serrate, acute at the apex, and displays 5–10 pairs of secondary nerves. The panicle is terminal, lateral, and 5–10 cm long. The calyx is cupular and 0.1 cm long. The corolla is absent. The pistillate flowers present a calyx that is tubular and 0.2 cm long. The fruits consist of 4-cm-long spatulate samaras (Figure 9.18).

FIGURE 9.18  Fraxinus chinensis Roxb.

331

Superorder Asteranae Takht., 1967

Medicinal use: In China, the samaras are used to to treat indigestion. Constituents: The plant abounds with iridoid glucosides such as frachinoside, neooleuropein, and oleuropein.148 Pharmacology: Fraxinus chinensis Roxb. contains the coumarins esculin and esculetin that showed remarkable antioxidant effects in the 2,2-diphenyl-1-picrylhydrazyl experiment. Moreover, treatment of UVA-irradiated human dermal fibroblasts with esculetin decreased the expression levels of MMP-1 mRNA and protein.149 Note that esculetin is known to inhibit the enzymatic activity of xanthine oxidase, the aggregation of platelets, and oxidation and to abrogate the survival of human breast cancer cells via apoptosis induction.150 Oleuropein has been shown to boost the enzymatic activity of pepsin and may be responsible for the digestive property of the plant.151 OH OH

O O

O

H3C

CH3 O



HO

OH HO

O

HO Oleuropein

O

OH O

HO



O

Esculetin

Bioresource: In vitro pharmacological study of esculetin for its effect on cancer. The next plant discussed in this section is Fraxinus malacophylla Hemsl. 9.2.3.1.3  Fraxinus malacophylla Hemsl. [From Latin Fraxinus = a classical Latin name for this genus, and from Greek malakos = soft, and phullon = leaf] History: This plant was first formally described in Hooker’s Icones Plantarum by William Botting Hemsley in 1899. Hemsley (1843–1924) was a British botanist. Common name: Bai qiang gan (Chinese). Synonym: Fraxinus retusifoliolata Feng ex P.Y. Bai. Habitat: It is a deciduous tree native to the forests of China and Thailand. The plant is ornamental. Diagnosis: Fraxinus malacophylla Hemsl. is 15 m tall. The stems are quadrangular and brown tomentose. The leaves are compound and 25 cm long. The petiole is 2–5 cm long. The rachis is densely brown tomentose, and carries 9–15 leaflets. The leaflets are sessile, elliptical or slightly cuneate, 3.5 cm × 1.5 cm to 8 cm × 4.5 cm, thinly leathery, cuneate at the base, acute at the apex, and display 7–10 pairs of secondary nerves. The inflorescence is a panicle that is terminal or lateral, 15 cm long, and densely flowered. The calyx is cupular and minute. The corolla is white. The corolla lobes are linear and 0.3 cm long. The stamens are expanding from the corolla. The samaras are 3 cm × 0.5 cm to 4 cm × 0.7 cm and spatulate (Figure 9.19). Medicinal uses: In China, this plant is used to treat malarial fever and as a laxative. It is also used to treat sore throat, bleeding, urogenital infection, flu, inflammation, and toothache.

332

Medicinal Plants of China, Korea, and Japan

FIGURE 9.19  Fraxinus malacophylla Hemsl.

Constituents: The plant produces series of iridoid glycosides such as butyl isoligustrosidate, fraximalacoside, isoligustroside, fraxiformoside, isoligustrosidic acid, 1″-O-beta-dglucosylfraxiformoside, cosmosiin, sitosterol-beta-d-glucoside, tyrosol, and verbascoside.152 Pharmacology: Apparently unknown, but one could infer that most of the medicinal properties listed above are owed to verbascoside. Verbascoside isolated from Tectona grandis L. f. (order Lamiales, family Lamiaceae) impaired the secretion of gastric juice via the inhibition of H+ K+-ATPase enzymatic activity.153 In addition, verbascoside isolated from Lepechinia speciosa (A. St.-Hil. ex Benth.) Epling (order Lamiales, family Lamiaceae) abrogated the survival of the herpes simplex virus cultured in vitro.154 O

OH O

H3C HO

HO OH

O HO

O O

O

OH OH OH Verbascoside

OH

Besides, verbascoside showed antiviral activity against the vesicular stomatitis virus cultured in vitro.155 Verbascoside isolated from Markhamia lutea (Benth.) K. Schum. (order Scrophulariales, family Bignoniaceae) exhibited dramatic in vitro activity against the respiratory syncytial virus.156

Superorder Asteranae Takht., 1967

333

Verbascoside isolated from Verbascum mallophorum Boiss. & Heldr. (order Scrophulariales, family Scrophulariaceae) mitigated the enzymatic activity of inducible nitric oxide synthase in human acute monocytic leukemia (THP-1) cells stimulated with bacterial lipopolysaccharides and interferon gamma.157 Moreover, verbascoside isolated from Buddleja globosa Hope (order Gentianales, family Gentianaceae) exhibited analgesic activity in the acetic acid-induced abdominal writhing experiment and the tail flick experiment.158 Finally, verbascoside isolated from Phlomis lanceolata Boiss. (order Lamiales, family Lamiaceae) showed considerable activities against a number of strains of multidrug-resistant Gram-positive Staphylococcus aureus.159 Bioresource: In vitro pharmacological study of verbascoside for its effect on skin ageing. The next plant discussed in this section is Jasminum multiflorum (Burm. f.) Andrews. 9.2.3.1.4  Jasminum multiflorum (Burm. f.) Andrews [From Latin jasminum = a late medieval Latin version of the Persian name yasmin, and multiflorum = with many flowers] History: This plant was first formally described in Flora indica: cui Accedit Series Zoophy­ torum Indicorum nec non Prodromus Florae Capensis by Nicolaas Burman in 1768. Burman (1734–1793) was a professor of botany at Amsterdam. Common names: Downy jasmine, star jasmine, angel hair jasmine, mao mo li (Chinese). Basionym: Nyctanthes multiflora Burm. f. Synonyms: Jasminum pubescens (Retz.) Willd., Nyctanthes pubescens Retz. Habitat: It is a climbing shrub native to India that is cultivated around the tropical and ­subtropical world as an ornamental plant.

FIGURE 9.20  Jasminum multiflorum (Burm. f.) Andrews. (From Det.: R. Kiew. Flora of Peninsular Malaysia. Singapore Botanic Gardens Herbarium. Loc.: Labu, Negeri Sembilan, Malaysia. Date: September 2003.)

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Medicinal Plants of China, Korea, and Japan

Diagnosis: Jasminum multiflorum (Burm. f.) Andrews is 4 m tall. The stems are terete and hairy. The leaves are opposite and simple. The petiole is 0.5–1 cm long and densely hairy. The blade is cordate at the base, acuminate at the apex, 3 cm × 1.5 cm to 10 cm × 5 cm, and papery. The blade shows 3–4 pairs of secondary nerves. The inflorescence is terminal and densely flowered. The calyx is densely hairy. The calyx tube is minute and develops 6–9 lobes that are filiform. The corolla is pure white and sweetly scented. The corolla tube is 1.5 cm long and presents 7–9 lobes that are acute and 1.5 cm long (Figure 9.20). Medicinal uses: In Burma, this plant is used to heal ulcers and as an antidote to snakebites. In Indonesia, this plant is prepared as tea and drunk to treat bladder disorders. This plant is also used to break fever and to treat malaria, kidney stones, diarrhea, stomachache, gastric ulcers, and jaundice. Pharmacology: The pharmacological property of Jasminum multiflorum (Burm.) f. Andrews is apparently insufficiently explored, but hepatoprotective, antidiarrheal, analgesic, woundhealing, and antiulcerogenic properties have been found in other members of the genus Jasminum L. Oleuropein isolated from Jasminum officinale L. inhibited the secretion of hepatitis B antigen by human hepatoma (HepG2 2.2.15) cells cultured in vitro with an IC50 value of 23.2 μg/mL. Besides, oleuropein inhibited the replication of the hepatitis B virus cultured in vitro.160 O

OCH3

O O

O O

OH

HO

HO Jasmolactone B

An extract of Jasminum amplexicaule Buch.-Ham. protected rodents against diarrhea induced experimentally by castor oil and magnesium sulfate, and exhibited analgesic properties in the acetic acid-induced abdominal writhing experiment.161 In addition, an extract of Jasminum grandiflorum L. exerted potent healing properties in the excision and dead space wound experiments.162 Moreover, an extract of the leaves of Jasminum grandiflorum L. exhibited antiulcerogenic activity in the aspirin-, pylorus ligation-, alcohol-, and acetic acid-induced ulcer experiments in rodents.163 Note that Jasminum multiflorum (Burm.) f. Andrews contains series of iridoid lactones such as jasmolactones B and D which induced vasodilation of the arteries.164 Bioresource: Phytochemical investigation and in vitro pharmacological study of oleuropein for its effect on hepatitis B. The next plant discussed in this section is Jasminum sambac (L.) Aiton. 9.2.3.1.5  Jasminum sambac (L.) Aiton [From Latin jasminum = a late medieval Latin version of the Persian name yasmin, and Sanskrit champaka = Michelia chempaca L.] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist.

Superorder Asteranae Takht., 1967

335

Common names: Arabian jasmine, mo li hua (Chinese). Basionym: Nyctanthes sambac L. Habitat: It is a climbing shrub native to India and is widely cultivated in the tropics as an ornamental plant. Diagnosis: Jasminum sambac (L.) Aiton is 3 m tall. The stems are terete and hairy. The leaves are simple and opposite. The petiole is 0.4 cm long, articulate, and hairy. The blade is ovate, 4 cm × 2.5 cm to 12.5 cm × 7.5 cm, papery, blunt at the apex, and presents 4–6 pairs of secondary nerves. The inflorescence is a terminal cyme of 3 flowers. The flowers are fragrant. The calyx presents 8–9 linear lobes that are 0.5 cm long. The corolla is pure white. The corolla tube is 1.5 cm long. The corolla lobes are oblong and 0.5 cm × 1.5 cm to 0.9 cm × 1.5 cm. The berry is purplish, globose, and 1 cm in diameter (Figure 9.21). Medicinal uses: In China, the roots are used as a sedative. In Cambodia, Laos, and Vietnam, the juice extracted from the leaves is used to treat inflammation of the eyes. In addition, it is used to break fever and to heal cracked lips. In Malaysia, this plant is used to assuage headache and to treat venereal diseases. In Indonesia, this plant is used to break fever. The flowers are used to make “jasmine tea” and the essential oil is used in aromatherapy to fight depression. Constituents: The roots contain dotriacontanoic acid, dotriacontanol, oleanolic acid, daucosterol, hesperidin, and iridoid glycosides.165,166 Pharmacology: The essential oil distilled from the flowers of Jasminum sambac (L.) Ait. contains linalool, methyl anthranilate, 4-hexanolide, 4-nonanolide, (E)-2-hexenyl hexanoate, and 4-hydroxy-2,5-dimethyl-3(2H)-furanone and is known to increase the autonomic arousal, alertness, and vigor in humans.167,168 In addition, the essential oil abrogated the survival of Gram-negative Escherichia coli cultured in vitro and may confer to the plant its anti-infectious property.169 Note that hesperidin isolated from Citrus sinensis (L.) Osbeck

FIGURE 9.21  Jasminum sambac (L.) Aiton. (From . Coll.: Barbon, Romero, and Fernando. Philippine Plant Inventory. Flora of the Philippines Joint Project of the Philippines National Museum, Manila and B.P. Bishop Museum, Honolulu, supported by NSF/USAID. No. 1833. Loc.: Philippines, Mindanao, Agusan Norte. Tungao, NALCO. Date: May 15, 1991.)

336

Medicinal Plants of China, Korea, and Japan

(order Sapindales, family Rutaceae) exhibited sedative property in rodents by a mechanism involving adenosine receptors, hence the sedative property of the roots.170 H3C

OH

CH2

H3C

CH3

Linalool OH

OH

O CH3 OH

OCH3

O OH

OH

O

O

O

OH OH OH

O

Hesperidin

Bioresource: In vitro pharmacological study of hesperidin as an anxiolytic agent. The next plant discussed in this section is Ligustrum lucidum W.T. Aiton. 9.2.3.1.6  Ligustrum lucidum W.T. Aiton [From Latin Ligustrum = a Latin name for the privet plant, and lucidum = glossy] History: This plant was first formally described in Hortus Kewensis by William Townsend Aiton in 1810. Aiton (1766–1849) was a Scottish botanist. Common names: Glossy privet, nu zhen (Chinese), to nezumimochi (Japanese), dang gwang na mu (Korean). Synonyms: Esquirolia sinensis H. Lév., Ligustrum compactum var. latifolium W.C. Cheng, Ligustrum esquirolii H. Lév., Ligustrum lucidum var. esquirolii (H. Lév.) H. Lév., Ligustrum lucidum var. latifolium (W.C. Cheng) P.S. Hsu. Habitat: It is a deciduous tree native to the forests of China. It is grown as a street and park ornamental plant and as a bonsai. Diagnosis: Ligustrum lucidum W.T. Aiton is 20 m tall. The stems are terete. The petiole is 1–3 cm long. The blade is broadly lanceolate, 5 cm × 3 cm to 15 cm × 8 cm, coriaceous, glossy, round at the base, acute at the apex, and displays 4–11 pairs of secondary nerves. The inflorescence is a terminal panicle that is 25 cm long. The flowers are sessile and small. The calyx is 0.2 cm long. The corolla is 0.4 cm long. The corolla tube is as long as the lobes. The stamens are as long as the corolla lobes. The anthers are 0.1 cm long. The berries are black, globose, and 1 cm in diameter (Figure 9.22). Medicinal uses: In China, the bark is boiled in water and the liquid obtained is drunk to promote sweating. The leaves are used to heal abscesses, to treat cold, congestions, swellings, and vertigo, to assuage headache, and to break fever. The fruits are used to cure fatigue, to check hemoptysis, to treat dropsy, and to promote longevity. Constituents: The fruits of Ligustrum lucidum W.T. Aiton accumulate a substantial amount of dammarane triterpenes as well as the flavonoids apigenin, cosmosiin, apigenin-7-O-acetyl-

Superorder Asteranae Takht., 1967

337

FIGURE 9.22  Ligustrum lucidum W.T. Aiton.

beta-d-glucoside, apigenin-7-O-beta-d-lutinoside, luteolin, luteolin-7-O-beta-d-glucopyranoside, and quercetin.171,172 Pharmacology: The anti-inflammatory property of Ligustrum lucidum W.T. Aiton is confirmed: extracts of fruits protected rodents against butylated hydroxytoluene-induced oxidative damage and inhibited the generation of tumor necrosis factor-alpha by mouse peritoneal macrophages stimulated with bacterial lipopolysaccharides.173,174 Iridoid glucosides may account for the anti-inflammatory property of the plant as nuezhenoside showed a significant antioxidant effect in the 2,2-diphenyl-1-picrylhydrazyl experiment.175 Oleoside dimethyl ester, oleuropein, neonuezhenide, lucidumoside B, and lucidumoside C protected red blood cells against free radicals-induced cellular damage.176 Oleuropein abrogated the survival of the respiratory syncytial virus and the human parainfluenza virus cultured in vitro with IC50 values of 23.4 and 11.7 μg/mL, respectively.177 The triterpene oleanolic acid extracted from the fruits lowered the glycemia of alloxan-induced diabetic rodents and increased the hepatic glutathione regeneration capacity in rodents.178,179 Finally, oleanolic acid, ursolic acid, and nuezhenide abrogated the mutagenic activity of benzo[a]pyrene in Gram-negative Salmonella typhimurium.180 Bioresource: In vitro pharmacological study of nuezhenoside for its effect on skin ageing. The next plant discussed in this section is Ligustrum sinense Lour. 9.2.3.1.7  Ligustrum sinense Lour. [From Latin Ligustrum = a Latin name for the privet plant, and sinense = from China] History: This plant was first formally described in Flora Cochinchinensis by João de Loureiro in 1790. Loureiro (1717–1791) was a Portuguese botanist. Common names: Chinese privet, xiao la (Chinese), jwi ttong na mu (Korean).

338

Medicinal Plants of China, Korea, and Japan

FIGURE 9.23  Ligustrum sinense Lour.

Synonym: Ligustrum indicum (Lour.) Merr. Habitat: This deciduous bush grows in the forests of China and Vietnam. It is cultivated as an ornamental plant and made into bonsai. Diagnosis: Ligustrum sinense Lour. is 3 m tall. The stems are terete and hairy. The petiole is 0.2–0.8 cm long. The blade is elliptical, 2 cm × 1 cm to 7 cm × 3 cm, coriaceous, cuneate at the base, acute at the apex, and displays 4–6 pairs of secondary nerves. The inflorescence is a terminal or axillary panicle that is 10 cm long and densely flowered. The calyx is 0.1 cm long and hairy. The corolla is 0.5 cm long and whitish. The anthers are minute. The fruits are globose and 0.8 cm in diameter (Figure 9.23). Medicinal use: In China, this plant is used to soothe sore throat. Pharmacology: Ligustrum sinense Lour. is probably anti-inflammatory because of 10-hydroxyl-oleuropein, a kaempferol derivative, and lariciresinol glycoside that prevented red blood cell hemolysis induced by free radicals.181 Oleanolic acid in the plant may contribute to the anti-inflammatory property.103 Bioresource: In vitro pharmacological study of 10-hydroxyl-oleuropein for its effect on skin ageing. The next plant discussed in this section is Myxopyrum nervosum Bl. 9.2.3.1.8  Myxopyrum nervosum Blume [From Greek myxa = slime, and pyros = wheat, and from Latin nervosum = having distinct veins or nerves] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië by Karl Ludwig von Blume in 1826. Blume (1796–1862) was deputy director of agriculture in Bogor. Common names: Akar kulawai, akar dudaro (Malay).

339

Superorder Asteranae Takht., 1967

FIGURE 9.24  Myxopyrum nervosum Bl. (From Coll.: R. Matamin. Plants of Borneo. No. 230. Loc.: Malaysia, Sabah, Kota Marudu District. Kampong Monggis. Date: April 25, 1996.)

Habitat: It is a large climbing shrub found in the rainforests of Malaysia and Indonesia. Diagnosis: The stems of Myxopyrum nervosum Blume are quadrangular. The leaves are opposite. The blade is coriaceous, 12 cm × 4.5 cm to 21 cm × 10 cm, broadly elliptical, acuminate at the apex, acute at the base, and presents 4–6 pairs of secondary nerves. The inflorescence is a densely flowered panicle. The calyx presents 4 lobes that are triangular and acuminate. The corolla is fleshy, urceolate, and produces 4 yellowish lobes. The berry is globose, dark green, and 1.5–2 cm in diameter (Figure 9.24). Medicinal uses: In Malaysia, this plant is used postpartum. In Indonesia, this plant is used to expel worms from the intestines, to break fever, and to treat rheumatism. Pharmacology: Apparently unknown. Myxopyrum nervosum Bl. probably contains some iridoid glycosides including myxopyroside as such compounds have been reported from Myxopyrum smilacifolium Bl.182,183 One might be curious to study Myxopyrum nervosum Bl for analgesics. OH H3CO

O

HO O

O

O

OH O

HO OH

CH3 O Myxopyroside

OH

340

Medicinal Plants of China, Korea, and Japan

Bioresource: In vitro pharmacological study of myxopyroside for its effect on skin ageing. Another plant used to treat rheumatism is Osmanthus fragrans (Thunb.) Lour., discussed next. 9.2.3.1.9  Osmanthus fragrans (Thunb.) Lour. [From Greek osme = fragrant, and anthos = a flower, and from Latin fragrans = fragrant] History: This plant was first formally described in Systemat Vegetabilium. Editio Decima Quarta by Carl Peter Thunberg in 1783. Thunberg (1743–1828) was a Swedish botanist. Common names: Sweet Osmanthus, fragrant olive, kimmokusei (Japanese), mu xi (Chinese). Basionym: Olea fragrans Thunb. Synonyms: Olea ovalis Miq., Osmanthus longibracteatus H. T. Chang, Osmanthus macrocarpus P. Y. Bai. Habitat: This bush is found in East Asia and is widely cultivated for the perfume and beauty of its flowers. Diagnosis: Osmanthus fragrans (Thunb.) Lour. is 5 m tall. The petiole is 0.8–1.2 cm long. The blade is elliptical, glossy, 7 cm × 2.5 cm to 14.5 cm × 4.5 cm, cuneate at the base, serrulate, acuminate at the apex, and presents 6–8 pairs of secondary nerves. The inflorescence is an axillary cyme that is densely flowered. The calyx is minute. The corolla is yellowish, 0.3 cm long, and develops 4 lobes. The corolla tube is minute and the lobes are somewhat fleshy. The stamens are attached to the middle of the corolla tube. The fruits are drupaceous, black, elliptical, and 1.5 cm long (Figure 9.25). Medicinal uses: In China, this plant is used to excite the discharge of urine and to treat rheumatism, irregular menses, and bruises. In Taiwan, this plant is used to treat cough and to

FIGURE 9.25  Osmanthus fragrans (Thunb.) Lour. (From Coll.: H.R. Tan. Flora of Singapore. Singapore Botanic Gardens Herbarium. Loc.: Singapore, SBG, EG7, planted, cultivated, near the plot signboard of coffee plants. Date: April 14, 2010.)

341

Superorder Asteranae Takht., 1967

heal boils. In Cambodia, Laos, and Vietnam, this plant is used to treat cough. The flowers are used to perfume tea. Pharmacology: An extract of flowers of Osmanthus fragrans (Thunb.) Lour. showed an antioxidant effect in the 2,2-diphenyl-1-picrylhydrazyl experiment. In addition, the extract protected primary cortical neurons of rodents against different types of chemical insults.184 Osmanthus fragrans (Thunb.) Lour. synthesizes the lignans phillyrin and verbascoside that are quite likely to be involved in the anti-inflammatory property mentioned above.185 Note that verbascoside extracted from Anisomeles indica (L.) Kuntze (order Lamiales, family Lamiaceae) inhibited the generation of nitric oxide, tumor necrosis factor-alpha and interleukin-12 by macrophages stimulated with bacterial lipopolysaccharides and interferon gamma.186 O H3CO

O

O OH O

HO

OCH3 H3CO

OH OH Phillyrin

Besides, verbascoside inhibited the multiplication of human promyelocytic leukemia (HL-60) cells achieving an IC50 value of about 30 μM through a mechanism involving the enzymatic activity of cyclin-dependent protein kinases.187 Moreover, verbascoside exhibited antiestrogen activity in human breast adenocarcinoma (MCF-7) and murine preosteoblastic (KS483) cells.188 Is verbascoside involved in the gynecological use of Osmanthus fragrans Lour.? Phillyrin protected hyperalimented rodents against obesity and high levels of serum triglyceride and cholesterol.189 Moreover, phillyrin exhibited anti-inflammatory, antiviral, and antioxidant activities and inhibited the enzymatic activity of phosphodiesterases.190 Note that lignan glycosides are common in the genus Osmanthus Lour.191,192 Bioresource: In vitro pharmacological study of phillyrin for its effect on neurodegeneration. Verbascoside is found in the next clade: the family Orobanchaceae. 9.2.3.2  Family Orobanchaceae Vent., 1799, nom. cons., the Broom-Rape Family The family Orobanchaceae consists of about 17 genera and 150 species of annual or perennial singular parasitic herbs that are often fleshy and without chlorophyll. The phenolic glycoside orobanchin, iridoids, tannins, and monoterpenoid alkaloids are common in members of this family. The leaves are reduced to mere alternate scales. The inflorescence is a terminal raceme or spike. The calyx is tubular and has 4–5 lobes. The corolla is tubular, bilabiate, curved, and develops 5 imbricate lobes. The stamens are attached to the corolla tube. The anthers are tetrasporangiate, dithecal, and open by longitudinal slits. The gynoecium consists of a pair of carpels united to form a compound, superior ovary with a slender style and a 2–4-lobed stigma. The fruits are capsular, loculicidal, and contain numerous seeds that are small and elliptical.

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Medicinal Plants of China, Korea, and Japan

The pharmacological potentials of members of the family Orobanchaceae are yet to be explored despite compelling preliminary evidence. Verbascoside isolated from Cistanches salsa (C.A. Mey) G. Beck shows various pharmacological activities, such as antitumor, antioxidant, anti-inflammatory, antinephritic, antimetastatic, and hepatoprotective activities.193 Of special interest is the fact that verbascoside abated the induction of apoptosis triggered by 1-methyl-4-phenylpyridinium ion in cerebellar granule neurons.194 Recently, it has been discovered that verbascoside and its aglycones protected primary cultures of rat cortical neurons from glutamate-induced cellular damage and research has also found that verbascoside attenuated scopolamine-induced memory impairment in rodents.195,196 In addition, it was found that verbascoside protected human neuroblastoma (SH-SY5) cells against beta-amyloid-induced cellular damage.197 The first plant discussed in this section is Aeginetia indica L. 9.2.3.2.1  Aeginetia indica L. [After Paulus Aegineta, a Greek medical doctor of the seventh century, and from Latin indica = from India] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Ye gu (Chinese), nanbangiseru (Japanese), ya go (Korean). Synonyms: Aeginetia japonica Siebold & Zucc., Orobanche aeginetia L., Phelipaea indica (L.) A. Spreng. ex Steud. Habitat: This strange annual parasitic herb grows in the grasslands of China, Taiwan, Bangladesh, Bhutan, Cambodia, India, Indonesia, Japan, Laos, Malaysia, Burma, Nepal, the Philippines, Sri Lanka, Thailand, and Vietnam. Diagnosis: Aeginetia indica L. is 45 cm tall. The root is fleshy. The stems are orangish and woody. The leaves are red, lanceolate, 0.5 cm × 0.2 cm to 1 cm × 0.5 cm, and glabrous. The flowers are solitary. The corolla is purple, bilabiate, campanulate, and 4.5 cm long. The tube is slightly curved. The corolla lobes are entire. The filaments are purple, 0.9 cm long, and glabrous. The anthers are yellow. The style is 1.5 cm long. The stigma is pale yellow. The capsules are conical and 3 cm long. The seeds are yellow, elliptical, and ­minute (Figure 9.26). Medicinal uses: In Cambodia, Laos, and Vietnam, a paste of this plant is applied to sores. In the Philippines, this plant is used to treat diabetes and dropsy. In Taiwan, this plant is used to cure liver diseases, cough, and arthritis. Constituents: Aeginetia indica L. produces a lactone, aeginetolide, as well as aeginetic acid, isoaucubin, hydroxybeta-ionone glucoside, aeginetoside, balanophonin 4-O-beta-Dglucopyranoside, balanophonin, and ficusal.198,199 Pharmacology: An extract of seeds protected rodents against syngeneic Meth A tumor cells by a mechanism implying the secretion of interleukin-2, interleukin-6, interferon-gamma, and tumor necrosis factor-alpha by CD4+ T lymphocytes.200,201 OH H3C CH3

CHO

OH O O HO

O CH3



Aeginetolide

OCH3



Ficusal

OCH3

Superorder Asteranae Takht., 1967

343

FIGURE 9.26  Aeginetia indica L. (From Flora of Malaya. Herbarium, Universiti Pertanian Malaysia. Loc.: Limestone hill, Wang Pisang, Perlis, Malaysia.)

Ficusal is probably antioxidant and therefore involved in the anti-inflammatory property of the plant. One might be curious to study the plant for antidiabetic and hepatoprotective properties. Bioresource: In vitro pharmacological study of ficusal for its effect on skin ageing. The next plant discussed in this section is Orobanche coerulescens Stephan. 9.2.3.2.2  Orobanche coerulescens Stephan [From Greek orobos = vetch, and anchein = to strangle, and from Latin coerulescens = bluish] History: This plant was first formally described in Species Plantarum. Editio Quarta by Christian Friedrich Stephan in 1800. Stephan (1757–1814) was a Russian botanist. Common names: Lie dang (Chinese), hama utsubo (Japanese), cho jong yong (Korean). Synonyms: Orobanche ammophila C.A. Mey., Orobanche bodinieri H. Lév., Orobanche canescens Bunge, Orobanche coerulescens var. albiflora Kuntze, Orobanche coerulescens var. korshinskyi (Novopokr.) Ma, Orobanche coerulescens var. pekinensis Beck, Orobanche korshinskyi Novopokr., Orobanche mairei H. Lév., Orobanche japonensis Makino, Orobanche nipponica Makino, Orobanche pycnostachya var. yunnanensis Beck. Habitat: This singular biennal herb is found in Japan, China, Kazakhstan, Korea, Kyrgyzstan, Mongolia, Nepal, Russia, Turkmenistan, and Europe. Diagnosis: Orobanche coerulescens Stephan is 50 cm tall. The stems are erect, orangish, hairy, and unbranched. The leaves are ovate and 1.5 cm × 0.5 cm to 2 cm × 0.7 cm. The inflorescence is a terminal raceme that is 25 cm long and densely flowered. The calyx is 1.5 cm long. The calyx lobes are lanceolate and 0.5 cm long. The corolla is dark blue, 2.5 cm long, constricted, and open upward. The upper corolla lip is bilobed. The filaments are 1.5 cm long and hairy. The anthers are ovoid, 0.2 cm long, and glabrous. The pistil is

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Medicinal Plants of China, Korea, and Japan

FIGURE 9.27  Orobanche coerulescens Stephan.

1.5 cm long. The ovary is elliptical. The stigma is bilobed. The capsules are ovoid and 1 × 0.4 cm. The seeds are elliptical and minute (Figure 9.27). Medicinal uses: In China and Japan, this plant is used to cure fatigue and to promote fertility. Constituents: Orobanche coerulescens Stephan contains beta-sitosterol, caffeic acid, protocatechuic aldehyde, phenylpropanoid glycosides, isoverbascoside, crenatoside, and verbascoside.202−204 Pharmacology: Note that an extract of Orobanche cumana Wallr. exhibited antifatigue and immunostimulating activities.205 One could infer that the androgenic and estrogenic properties of Orobanche coerulescens Stephan involve iridoids. Bioresource: Estrogenic iridoid(s). Estrogenic iridoids are present in the next clade: the family Plantaginaceae. 9.2.3.3  Family Plantaginaceae Juss. 1789, nom. cons., the Plantain Family The family Plantaginaceae is a vast clade that consists of about 90 genera and 1500 herbs. The leaves are simple and without stipules. The flowers are minute, innumerable, and packed in spikes. The calyx, corolla, and androecium are tetramerous. The corolla lobes are imbricate. The stamens alternate with the lobes of the corolla tube. The filament is attached to the corolla tube. The anthers are tetrasporangiate and dithecal. The gynoecium consists of a pair of carpels fused to form a bilocular superior ovary. The fruits are capsular, circumscissile, and contain numerous tiny mucilaginous seeds. Several medicinal products belong to the genus Plantago L. The seeds of Plantago psyllium L. (sand Plantain), Plantago arenaria Waldst. & Kit. (branched Plantain), and Plantago indica L.

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(Psyllium, British Pharmaceutical Codex, 1963) are used as demulcent. The seeds absorb and retain water and are therefore used as a bulk-providing medium in the treatment of chronic constipation. Plantago major L. (Japanese Pharmacopoeia, 1962) is used in Japan for the same purpose. Plantago coronopus L. (Buck’s-Horn Plantain) has been used in Europe to dissolve renal calculi and promote urination. Several slimming and laxative preparations containing Plantago seeds are available. Of recent interest is the fact that Plantago species have shown promising anticholesterolemic, antidiabetic, anti-obesity, and antitumoral effects experimentally.206−210 O

OH

HO

O OH

O HO HO

HO

OH

HO

OH

O

O

HO HO

HO Aucubin

Catalpol

Note the presence of the iridoids aucubin and catalpol in Callitriche stagnalis Scop., discussed here.211 9.2.3.3.1  Callitriche stagnalis Scop. [From Greek kalli = beautiful, and thrix = hair, and from Latin stagnalis = found in stagnant water] History: This plant was first formally described in Flora Carniolica, Editio Secunda of Giovanni Antonio Scopoli in 1772. Scopoli (1723–1788) was an Italian botanist. Common names: Pond water starwort, common water-starwort. Habitat: This discrete perennial aquatic weed grows in ponds, lakes, and slow-moving rivers and is found in a geographical area covering Europe, North and East Africa, Asia, Australia, and New Zealand. Diagnosis: Callitriche stagnalis Scop. is 45 cm long. The stems are slender and stoloniferous. The leaves are 0.9 cm × 0.1 cm to 4 cm × 0.5 cm, decussate, fleshy, somewhat spongy, and form a floating rosette. The submerged leaves are sessile. The floating leaves have a short petiole. The blade is spatulate. The flowers are arranged in pairs and are sessile. The male flowers comprise a pair of 0.1-cm-long bracts and a 0.2-cm-long single stamen. The female flowers comprise a pair of oblong bracts that are obtuse, truncate, and 0.2 cm × 0.1 cm. The gynoecium comprises a pair of styles that are filiform and 0.3 cm long. The fruits are a minute schizocarps (Figure 9.28). Medicinal use: In Cambodia, Laos, and Vietnam, this plant is used to induce menses. Constituents: The plant contains series of iridoids such as aucubin and catalpol.211 Pharmacology: Apparently unknown, but the medicinal use could involve aucubin. An extract of Vitex agnus-castus L. (order Lamiales, family Verbenaceae) containing mainly aucubin displayed estrogenic activity. The extract triggered a noteworthy increase in the uterine weight of ovariectomized rodents and increased plasma progesterone and total estrogens levels.212 Is aucubin estrogenic? Bioresource: In vitro pharmacological study of aucubin for its effect on postmenopausal disorders. The next clade discussed in this chapter is the order Solanales.

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FIGURE 9.28  Callitriche stagnalis Scop. (From Coll.: T. Tanaka & T. Shimada. Flora of Taiwan. No. 13530. Loc.: Japan, Toyen, Shinchiku-shu. Date: April 3, 1933.)

9.2.4  Order Solanales Juss. ex Bercht. & J. Presl, 1820 The order Solanales consists of five families of flowering plants of which the Hydrophylleaceae is discussed here. 9.2.4.1  Family Hydrophyllaceae R.Br. 1817, nom. cons., the Waterleaf Family The family Hydrophyllaceae consists of about 20 genera and 250 species of herbs. The leaves are alternate, simple, or compound and without stipules. The inflorescence is a cyme or a panicle. The flowers are perfect, sympetalous, and pentamerous. The calyx is cleft to the base and presents imbricate segments. The corolla is regular. The corolla lobes are imbricate. The stamens are as many as and alternate with the corolla lobes. The anthers are tetrasporangiate, dithecal, and open by longitudinal slits. The gynoecium consists of a pair of carpels united to form a compound, superior unilocular ovary. The style is deeply bifid. The fruits are loculicidal capsules containing many seeds. An example of Hydrophyllaceae is Nemophila menziesii Hook. & Arn. (baby blue-eyes). OH

CH3

CH3 CH3

OH Phacelioid

Superorder Asteranae Takht., 1967

347

FIGURE 9.29  Hydrolea zeylanica (L.) Vahl. (From Coll.: G. Seidenfaden. Det.: M.R. Henderson. Flora of Siam. Lower Siam. No. 2241. Loc.: Thailand, Wat Sa Uhm, Bandon River (Surat). Date: January 8, 1935.)

Hydrophyllaceae are interesting because they contain a kind of uncommon alkylated hydroquinone called “phacelioids.” One such compound is geranylhydroquinone obtained from Phacelia crenulata Torr.213 Some of these compounds are equivalent to the urushiols of Toxicodendron sp. (order Sapindales, family Anacardiaceae) in their capacity to induce allergic reactions.214 The pharmacological potentials of this family are yet to be explored. Hydrolea zeylanica (L.) Vahl is examined in this section. 9.2.4.1.1  Hydrolea zeylanica (L.) Vahl [From Greek hydro = water, and eleia = olive, and from Latin zeylanica = from Ceylon] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Ceylon Hydrolea, tian ji ma (Chinese). Basionym: Nama zeylanica L. Synonyms: Beloanthera oppositifolia Hassk., Hydrolea arayatensis Blanco, Hydrolea inermis Lour., Hydrolea javanica Blume, Hydrolea zeylanica var. ciliata Choisy, Steris aquatica Burm. f., Steris javana L. Habitat: This perennial herb grows in paddy fields, on pond margins, river banks, and in swamps and is found in China, Taiwan, India, Indonesia, Burma, Malaysia, Nepal, the Philippines, Sri Lanka, Africa, Southwest Asia, and Australia. Diagnosis: The stems of Hydrolea zeylanica (L.) Vahl are prostrate, stoloniferous, 50 cm long, and branched. The blade is sessile, elliptical, 2 cm × 0.5 cm to 10 cm × 2.5 cm, and acute at the base and at the apex. The flowers are arranged in terminal panicles. The calyx

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Medicinal Plants of China, Korea, and Japan

lobes are lanceolate and 0.8 cm long. The corolla is purple, 0.5 cm long, and develops 5 lobes. The anthers are white. The capsules are ovoid, dehiscent, and included in the persistent calyx. The seeds are ovoid and minute (Figure 9.29). Medicinal use: In Burma and India, the leaves are reduced into a paste that is applied to putrefied ulcers. Pharmacology: Apparently unknown, but one could contemplate the role of some phenolic substances in the antiseptic use of the plant as phenolics compounds of pharmacological interest appear to abound in the family. Such compounds have been isolated from Wigandia urens (Ruiz & Pav.) Kunth (order Solanales, family Hydrophyllaceae) and Wigandia caracasana Kunth (order Solanales, family Hydrophyllaceae).215,216 Note that series of flavonoids have been isolated from the genus Eriodyction Benth. in de Candolle (order Solanales, family Hydrophyllaceae) including apigenin, luteolin, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside.217 Apigenin has been reported to possess antibacterial property and may be responsible for the antiseptic property of Hydrolea zeylanica (L.) Vahl.218 Bioresource: In vitro pharmacological study of apigenin for its effect on acne and cosmetological investigation of the plant for anti-wrinkle agents. Flavonoids abound in the next clade: Euasterids II.

9.3  EUASTERIDS II Euasterids II (Campanuliids) and Euasterids I share an ancestor from which they have inherited the ability to produce iridoids and terpenes of pharmacological interest. Besides, Euasterids II do not accumulate tannins and are known to contain sesquiterpenes, alkaloids, phenolic glycosides, coumarins, and polyynes that await pharmacological studies for their effect on cancer, viral, and bacterial infections as well as malaria, inflammation, Alzheimer’s disease, and skin ageing. Cytotoxic: In a cytotoxic assay with the human epithelial cancer (HeLa S3) cells, the iridoid derivatives luzonial A and B isolated from Viburnum luzonicum Rolfe (order Dipsacales, family Adoxaceae) exhibited some levels of activity with IC50 values of 3.5 and 1.9 μM, respectively.219 A sesquiterpene isolated from the roots of Ferula varia Trautv. (order Apiales, family Apiaceae) was significantly and specifically cytotoxic against multidrugresistant human epidermoid carcinoma of the nasopharynx (KB-C2) cells with an IC50 value of 17.5 μg/mL.220 The sesquiterpenes pancherins A and B isolated from Pittosporum pancheri Brongn. & Gris (order Apiales, family Pittosporaceae) exhibited IC50 values of 3.5 × 10 −1 and 5.1 × 10 −6 M, respectively, against human nasopharyngeal carcinoma KB cells.221 The triterpene saponins giganteoside D and E isolated from the roots of Cephalaria gigantea (Ledeb.) Bobrov. (order Dipsacales, family Caprifoliaceae) inhibited the growth of human nonpigmented melanoma (MEL-5) and human promyelocytic leukemia (HL-60) cells with IC50 values of 7.5 and 3.1 μM and 7.5 and 6.8 μM, respectively.222 The triterpene saponin acankoreoside isolated from the leaves of Acanthopanax koreanum Nakai (order Apiales, family Araliaceae) was cytotoxic against human lung adenocarcinoma epithelial (A549), human acute promyelocytic leukemia (HL-60), and human breast adenocarcinoma (MCF-7) cells with IC50 values of 8.2, 12.1, and 28.6 μM, respectively.223 The cyclofuran derivative 13-acetoxyrolandrolide isolated from the aerial parts of Rolandra fruticosa (L.) Kuntze (order Asterales, family Asteraceae) possessed a potent inhibitory effect against human colon cancer (HT-29) cells with an ED50 value of 0.1 μM.224 Antibacterial, antifungal: The polyyne falcarinol isolated from the inner bark of Oplopanax horridus (Sm.) Miq. (order Apiales, family Araliaceae) exhibited antibacterial properties against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis with ­minimum

Superorder Asteranae Takht., 1967

349

inhibitory concentrations of 6.2 and 3.1 μg/mL, respectively.225 The diterpene 15-pimaradien-3-beta-ol isolated from the roots of Viguiera arenaria Baker (order Asterales, family Asteraceae) inhibited Gram-positive Streptococcus dysgalactiae growth with a minimum inhibitory concentration of 1.5 μg/mL.226 The polyynes falcarindol and oplopandiol isolated from the stem bark of Oplopanax horridus (Sm.) Miq. (order Apiales, family Araliaceae) were active against Mycobacterium tuberculosis with minimum inhibitory concentrations of 61.5and 6.2 μg/mL.227 The triterpene saponin scoposide A isolated from the aerial parts of Cephalaria scoparia Contrandr. & Quezel (order Dipsacales, family Caprifoliaceae) inhibited the growth of Gram-negative Escherichia coli with a minimum inhibitory concentration of 8 μg/mL.228 Antiviral: The iridoid valtrate isolated from the roots of Valeriana fauriei Briq. (order Dipsacales, family Caprifoliaceae) inhibited p-24 production by human immunodeficiency virus-infected MT-4 cells cultured in vitro by 44% at a dose of 0.5 μM.229 The phenolics 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid isolated from the petioles of Schefflera heptaphylla (L.) Frodin (order Apiales, family Arialiaceae) protected human larynx epidermoid carcinoma cells against respiratory syncytial virus insults with IC50 values of 2.3 and 1.1 μM, respectively.230 The benzofuran wedelolactone isolated from the whole Eclipta prostrata (L.) L. (order Asterales, family Asteraceae) inhibited the enzymatic activity of human immunodeficiency virus integrase with an IC50 value of 4 μM.231 The coumarin 5′-hydroxyumbelliprenin isolated from the resin of Ferula assafoetida L. (order Apiales, family Apiaceae) was active against the influenza virus (H1N1) with an IC50 value of 0.9 μg/mL.232 Parasiticidal: The coumarins auraptene and umbelliprenin isolated from the roots of Ferula szowitsiana DC. (order Apiales, family Apiaceae) inhibited the growth of Leishmania major with IC50 values of 17.1 and 13.3 μM, respectively.233 Polyynes isolated from the root bark of Cussonia zimmermannii Harms (order Apiales, family Araliaceae) exhibited parasiticidal effects against Trypanosoma brucei rhodesiense, Plasmodium falciparum, Trypanosoma cruzi, and Leishmania donovanii with IC50 values of 0.4, 1.4, 0.6, and 0.1 μg/ mL, respectively.234 The sesquiterpene lactone 4-hydroxyanthecotulide isolated from Anthemis auriculata Boiss. (order Asterales, family Asteraceae) displayed potent antiprotozoal activity against Trypanosoma brucei rhodesiense with an IC50 value of 0.5 μg/ mL.235 A lactone isolated from the whole Carpesium divaricatum Siebold & Zucc. (order Asterales, family Asteraceae) showed an antiplasmodial property against Plasmodium falciparum with an IC50 value of 2.3 μM.236 Leishmania braziliensis was highly sensible to the flavonoid pectolineragenin isolated from the aerial parts of Baccharis uncinella DC. (order Asterales, family Asteraceae) showing an IC50 of 110 μg/mL.237 The coumarin (+)-3′-decanoyl-cis-khellactone isolated from the rhizomes of Angelica sp.(order Apiales, family Apiaceae) exhibited an antiplasmodial property against Plasmodium falciparum with an IC50 value of 1.5 μM.238 Anti-inflammatory: A coumarin isolated from the aerial parts of Ligusticum lucidum subsp. cuneifolium Tammaro (order Apiales, family Apiaceae) at a dose of 0.3 μmol/cm2 protected rodents against croton oil-induced ear edema.239 Central nervous system: The sesquiterpene madolin A isolated from the roots of Valeriana officinalis var. latifolia Miq. (order Dipsacales, family Caprifoliaceae) inhibited the enzymatic activity of acetylcholinesterase to 25.9% at a dose of 100 μM.240 Cosmetology: The triterpenes hederagenin and oleanolic acid isolated from Hedera helix L. (order Apiales, family Araliaceae) inhibited the enzymatic activity of hyaluronidase and elastase with IC50 values of 280.4 and 300.2 μM and 40.6 and 5.1 μM, respectively.241 The sesquiterpene inuviscolide isolated from Inula viscosa (L.) Aiton (order Asterales, family Asteraceae) inhibited the enzymatic activity of elastase by 51% at 100 μM.242 Dicaffeoylquinic acid derivatives and flavonoids isolated from Ilex paraguariensis A.

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Medicinal Plants of China, Korea, and Japan

­ t.-Hil. (order Aquifoliales, family Aquifoliaceae) inhibited the enzymatic activity of S ­elastase inhibitory activity with IC50 values of 1.4–7.3 μM.243 The sesquiterpene podachaenin from Podachaenium eminens (Lag.) Sch. Bip. (order Asterales, family Asteraceae) inhibited the enzymatic activity of elastase with an IC50 value of 7 μM.244,245 Euasterids II consist of the orders Aquifoliales, Asterales, Escalloniales, Bruniales, Paracryphia­ les, Apiales, and Dipsacales. The orders Asterales and Apiales are examined in this section.

9.3.1  Order Asterales Link, 1829 The order Asterales consists of eight families of flowering plants of which the Campanulaceae is discussed here. 9.3.1.1  Family Campanulaceae Juss., 1789, nom. cons., the Bellflower Family The family Campanulaceae consists of about 70 genera and 2000 species of campanula-like herbs known to produce piperidine alkaloids, polyynes, and pentacyclic triterpene saponins. The leaves are simple, alternate or opposite, and without stipules. The flowers are showy, actinomorphic, tubular, and epigynous. The calyx comprises 5 lobes that are imbricate or valvate. The corolla is tubular, bellshaped, and produces 5 lobes. The corolla lobes are valvate. The androecium consists of 5 stamens alternate with the corolla lobes. A nectary disc is present. The gynoecium consists of 2–3 carpels united to form a compound 2–3-locular ovary. The fruits are capsular and enclosed in the calyx. O

H

OH

N CH3

Lobeline

Classical examples of the subfamily Lobeliaceae are Campanula medium L. (Canterbury Bell) and Campanula rotundifolia L. (bluebell). An example of medicinal Lobeliaceae is Lobelia inflata L. or Indian tobacco (Lobelia, British Pharmaceutical Codex, 1963), an annual herb indigenous to the eastern United States and Canada, the aerial parts of which contains the piperidine alkaloid lobelin. Lobelin is a nicotine antagonist that has been used as a respiratory stimulant for the resuscitation of newborn and as smoking deterrent. Other examples of medicinal Lobeliaceae are Lobelia nicotianifolia Roth and Lobelia chinensis Lour. that are used in India and China, respectively. A saponin isolated from the roots of Codonopsis lanceolata (Siebold & Zucc.) Trautv. was cytotoxic against cancer cells via apoptosis induction.246 The first plant examined in this section is Codonopsis pilosula (Franch.) Nannf. 9.3.1.1.1  Codonopsis pilosula (Franch.) Nannf. [From Latin codonopsis = bell-like, and pilosula = somewhat hairy] History: This plant was first formally described in Plantae Davidianae ex Sinarum Imperio by Adrien René Franchet in 1884. Franchet (1834–1900) was a French botanist. Common names: Bonnet bellflower, poor man’s ginseng, dang shen (Chinese), tojin (Japanese), man sam (Korean). Basionym: Campanumoea pilosula Franch. Habitat: It is a perennial climber that grows in the mountain forests of Korea and China.

Superorder Asteranae Takht., 1967

351

FIGURE 9.30  Codonopsis pilosula (Franch.) Nannf.

Diagnosis: Codonopsis pilosula (Franch.) Nannf. is 2 m long. The root is tuberous and 35 cm long. The plant has a peculiar smell when crushed. The leaves are simple, alternate, and without stipules. The blade is ovate, crenate, 5 cm × 3.5 cm, obtuse at the base, and hairy. The flowers are solitary on elongate peduncles. The calyx has 5 lobes. The calyx lobes are leaf-like. The corolla is campanulate, with 5 lobes, greenish purplish, and 2.5 cm × 1.5 cm. The stigmas are showy. The androecium includes 5 stamens. The fruits are capsular and 2.5 cm in diameter (Figure 9.30). Medicinal uses: In Korea, the roots are used to cure fatigue, gonorrhea, and lung and urogenital diseases. In China, the roots are used to cure fatigue, to promote the growth of red blood cells, to stimulate the production of saliva, to treat syphilis, to stimulate venereal appetite, to replace ginseng, to calm, to regulate menses, and to treat cancer of the breast. Pharmacology: Codonopsis pilosula (Franch.) Nannf. stores some alkaloids that enhanced neurite outgrowth of rat pheochromocytoma (PC12) cells cultured in vitro.247 Besides, an extract of the plant elicited some levels of gastroprotective activity in the stress, acetic acid, and sodium hydroxide experiments.248 This plant is also known to contains the phenolic glycoside tangshenoside I that is probably antioxidant.249 One might be curious to look for cytotoxic agents in this plant. Bioresource: In vitro pharmacological study of total alkaloids isolated from Codonopsis ­pilosula (Franch.) Nannf. for their effects on neurodegeneration. The next plant discussed in this section is Pentaphragma begoniifolium Wall. 9.3.1.1.2  Pentaphragma begoniifolium Wall. [From Greek pente = five, and phragma = hedge, and from Latin begoniifolium = with begonia-like leaves]

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Medicinal Plants of China, Korea, and Japan

FIGURE 9.31  Pentaphragma begoniifolium Wall. (From Coll.: K. Hisham, K. Imin, C.L. Lim, and T.L. Yao. Flora of Malaya. Forest Research Institute Malaysia (KEP). Kepong, Malaysia. Loc.: Lata Kekabu, Bintang Hijau Forest Reserve, Hulu Perak, Perak, Malaysia, 5°03.01′N–100°56.39′E. Alt.: 252 m.)

History: This plant was first formally described in Malayan Miscellanies by William Roxburgh in 1820. Roxburgh (1751–1815) was a Scottish botanist. Common name: Salang suang (Malay). Basionym: Phyteuma begoniifolium Roxb. ex Jack. Habitat: It is a rare and odd perennial herb that grows in the lowland rainforests of Malaysia. Diagnosis: Pentaphragma begoniifolium Wall. is 40 cm tall. The stems are fleshy and woolly. The leaves are alternate. The blade is reniform, glossy, dark green, serrate, and 12 cm × 10 cm to 18 cm × 10 cm. The petiole is 3 cm long. The inflorescence is a peculiar scorpioid cyme that is 3–15 cm long. The bracts are ovate and 0.7 cm long. The bracteoles are oblong, hairy, and 0.6 cm long. The calyx is hairy on the outside. The corolla is glabrous, campanulate, whitish, and develops 5 lobes. The berries are quadrangular (Figure 9.31). Medicinal use: In Malaysia, a paste of the roots is applied to swellings. Pharmacology: The genus Pentaphragma Wall. ex G. Don apparently has not yet been studied for pharmacology. Bioresource: Phytochemical and pharmacological investigations and anti-inflammatory-agent(s). The next plant discussed in this section is Platycodon grandiflorus (Jacquin) DC. 9.3.1.1.3  Platycodon grandiflorus (Jacquin) DC. [From Greek platys = broad, and kodon = bell, and from Latin grandiflorum = with large flower] History: This plant was first formally described in Monographie des Campanulées by Nikolaus Joseph Freiherr von Jacquin in 1830. Jacquin (1727–1817) was a Dutch botanist. Common names: Balloon flower, jie geng (Chinese), asagao (Japanese), do ra ji (Korean). Synonyms: Campanula glauca Thunb., Campanula grandiflora Jacq., Platycodon autumalis Decne., Platycodon chinensis Lindl. & Paxton, Platycodon glaucus (Siebold & Zucc.) Nakai, Platycodon grandiflorus var. glaucus Siebold & Zucc.

Superorder Asteranae Takht., 1967

353

FIGURE 9.32  Platycodon grandiflorus (Jacquin) DC. (From Leg.: T. Buch & M. Guseva. Det.: S. Kharkevich. Plantae Vasculares Orientis Extremi Rossici (VLA) Flora Exsiccata. Loc.: Russia, Primorskiy territory, Mikhaylovski district, to 56 km of village Mikhaylovka, roadside, abundant. Date: August 10, 1983.)

Habitat: This perennial herb grows in open grassy areas in the hills of China, Korea, and Japan. Diagnosis: Platycodon grandiflorus (Jacquin) DC. is 1 m tall. The root is pure white and anthropomorphic. The stems are glabrous, erect, and branched at the apex. The leaves are simple and alternate. The blade is ovate, 4 cm × 1.5 cm to 7 cm × 4 cm, dentate, and glaucous below. The flowers are solitary and showy. The flower buds are peculiarly balloonshaped or bulbous. The corolla is broadly campanulate, bluish, and 5 cm in diameter. The stamens are white. The gynoecium comprises 5 white stigmas (Figure 9.32). Medicinal uses: In China, the plant is used to cure fatigue, to expel worms from the intestines, and to treat cholera, indigestion, dysentery, colds, bleeding from the lungs, sore throat, asthma, and gastric ulcers. In Japan, this plant is used to treat lung diseases. Constituents: Platycodon grandiflorum (Jacquin) DC. accumulates series of oleananes saponins known as platycosides.250−252 Pharmacology: The use of the plant to treat cough could involve saponins that are mucolytic. The anti-inflammatory property of the plant is confirmed: oral administration of saponins extracted from the plant abrogated the dinitrophenyl-immunoglobulin E antibody-induced systemic anaphylactic reaction in rodents.253 The gastroprotective effect of the plant is confirmed as saponins extracted from the roots protected rodents against ethanol-induced hepatocellular damage.254 In addition, saponins isolated from the plant lowered the total cholesterol levels in plasma and liver of rodents on a high-fat diet.255 Moreover, saponins isolated from the plant abrogated the survival of colon cancer (HT29) cells cultured in vitro via apoptosis induction.256 Finally, saponins extracted from the plant improved the memory of rodents intoxicated with ethanol in the passive avoidance task experiment.257 Bioresource: Neuropharmacological investigation. Saponins are common in the next clade: the order Apiales.

354

Medicinal Plants of China, Korea, and Japan

9.3.2  Order Apiales Nakai, 1930 The order Apiales consists of six families of flowering plants of which the Apiaceae is discussed here. 9.3.2.1  Family Apiaceae Lindl., 1836, nom. cons., the Carrot Family The family Apiaceae consists of about 300 genera and 3000 species of aromatic, often poisonous, perennial herbs best developed in north temperate regions. Apiaceae are mainly known to produce polyynes, triterpene, and coumarins of pharmacological value. The leaves are alternate, pinnately or ternately compound or dissected, and without stipules. The inflorescence is a very characteristic umbel. The flowers are small, perfect, and pentamerous. The calyx consists of 5 small teeth. The corolla presents 5 petals that are often white, asymmetrical, and valvate. The androecium comprises 5 conspicuous stamens. The anthers are tetrasporangiate, dithecal, and open by longitudinal slits. The gynoecium consists of a pair of carpels united to form a compound, inferior, bilocular ovary. The fruits are dried schizocarps consisting of a pair of mericarps separating at maturity. The seeds are oily and aromatic. Many species in this family are cultivated for food or spice. Daucus carota L. is the carrot. Dill oil (British Pharmaceutical Codex, 1963) is the oil obtained by distillation of the seeds of Anethum graveolens L. Dill oil, usually in the form of dill water, is used as an aromatic carminative, especially in the treatment of flatulence in infants. Apiol (British Pharmaceutical Codex, 1934) is an oil obtained by alcoholic extraction from the seeds of parsley, Petroselinum crispum (Mill.) Nyman. Apiol has been used as an emmenagogue but is of doubtful therapeutic value. Celery (British Pharmaceutical Codex, 1949) consists of the seeds of Apium graveolens L. It has been reputed to have a sedative effect on the nervous system but it is of doubtful therapeutic value. Caraway (British Pharmacopoeia, 1963) consists of the dried ripe fruits of Carum carvi L. that are aromatic and carminative on account of carvone. Coriander or Coriandrum sativum L. produces coriander oil that is carminative on account of alpha-pinene. Conium leaf (British Pharmaceutical Codex, 1949) consists of the leaves of Conium maculatum L. containing about 0.2% of total alkaloids, chiefly coniine. Coniine is a very poisonous piperidine alkaloid that provokes paralysis of the nervous system and of the skeletal muscle nerve endings. It has been used in chorea, mania, paralysis agitans, and spasmodic affection such as whooping cough and asthma. Anise (British Pharmaceutical Codex, 1954) consists of the fruits of Pimpinella anisum L., containing not less that 2% of essential oil including anethol. It has been used to cure flatulence and cough.

N H

H Coniine

CH3

CH3 CH3 HO H3C

H CH3

O

O NH2

Elaeochytrin A

355

Superorder Asteranae Takht., 1967 OCH3 O

O

OCH3

OCH3 O

H3CO CH3

O



Isochaihulactone



Anethol

Centella (Indian Pharmaceutical Codex, 1955) consists of the leaves of Centella asiatica (L.) Urb. that contain asiaticoside. It has been used to treat skin diseases and as a diuretic. It has long been a popular remedy in India for leprosy and syphilis. A sesquiterpene ester elaeochytrin A extracted from the roots of Ferula elaeochytris Korovin inhibited the growth of imatinib-resistant human erythromyeloblastoid leukemia (K562R) cells achieving an IC50 value of 12.4 μM.258 Triterpene saponins isolated from the roots of Physospermum verticillatum Vis, identified as saikosaponin a, buddlejasaponin IV and songarosaponin D exhibited a dramatic cytotoxic activity against human lung carcinoma (COR-L23) cells cultured in vitro with IC50 values of 0.4– 0.6 μM.259 Saikosaponins, the main active constituents of members of the genus Bupleurum L., have been shown to possess immunomodulatory, hepatoprotective, antitumor, and antiviral properties.260 The essential oils of Ridolfia segetum (L.) Moris and Oenanthe crocata L. inhibited the enzymatic activity of human immunodeficiency virus RNA-dependent DNA polymerase.261 Isochaihulactone isolated from Bupleurum scorzonerifolium Willd. abrogated the survival of a broad spectrum of human tumor cells with IC50 values of 10–50 μM via inhibition of tubulin polymerization.262 The first plant discussed in this section is Angelica acutiloba (Siebold & Zucc.) Kitag. 9.3.2.1.1  Angelica acutiloba (Siebold & Zucc.) Kitag. [From Latin angelica = referring to the medicinal properties of the plant that are said to have been revealed to a monk by an angel who told him it was a cure for malarial fever, and acutiloba = with acute lobes] History: This plant was first formally described in Florae Japonicae Familae Naturales Adjectis Generum et Specierum Exemplis Selectis by Philipp Franz Balthasar von Siebold and Joseph Gerhard Zuccarini in 1845. Siebold (1796–1866) and Zuccarini (1706–1848) were German botanists. Common names: Japanese angelica, dong dang gui (Chinese), yamato toki (Japanese), wae dang gwi (Korean). Basionym: Ligusticum acutilobum Siebold & Zucc. Habitat: This perennial herb grows on the mountains of Japan and Korea. Diagnosis: Angelica acutiloba (Siebold & Zucc.) Kitag. is 1.5 m tall. The root is yellow, conical, 10 cm × 1 cm to 25 cm × 2.5 cm, and strongly aromatic. The stems are sturdy, purplish, and ribbed. The basal and lower leaves are petiolate. The petiole is 15–30 cm long. The blade is triangular, 25 cm long, pinnate, and glabrous. The pinnae are 2 cm × 1 cm to 9 cm × 3.5 cm and trilobed. The lobes are lanceolate, serrate, and acuminate at the apex. The peduncles are 5–15 cm long. The bracts are linear and 2 cm long. The rays are 18–30 in number, unequal, and hairy. The bracteoles are linear and 1.5 cm long. The umbellules have 30 flowers. The pedicels are slender. The calyx teeth are inconspicuous. The petals are pure white and obovate. The fruits are oblong and 0.5 cm × 0.1 cm (Figure 9.33).

356

Medicinal Plants of China, Korea, and Japan

FIGURE 9.33  Angelica acutiloba (Siebold & Zucc.) Kitag.

Medicinal uses: In Japan, this plant is used to induce menses and to promote the formation of blood, and is given during parturition. In Cambodia, Laos, and Vietnam, this plant has similar uses and is also used to treat indigestion. In Indonesia, this plant is used to excite the discharge of urine, to alleviate birth pain, and to treat vertigo. Constituents: Butylidene phthalide and ligustilide are the main constituents of the essential oil extracted from the roots of Angelica acutiloba (Siebold & Zucc.) Kitag.263 Pharmacology: Note that an extract of roots (300 mg/kg per day) protected rodents against obesity induced by a high-fat diet.264 An extract of the plant inhibited Epstein–Barr virus activation induced by 12-O-tetradecanoylphorbol-13-acetate probably on account of butylidene phthalide and ligustilide that exhibited cytotoxic activities against human colon ­cancer (HT-29) cells cultured in vitro achieving IC50 values of 236 and 60.6 μM, respectively.265,266 Butylidene phthalide isolated from this plant abrogated the survival of larvae of Drosophila melanogaster.267 The plant could be used to treat dizziness as a symptom of hypertension, because of butylene phthalide and ligustilide. CH3

CH3 O



O Butylidene phthalide

O



O Ligustilide

Note that ligustilide significantly mitigated phenylephrine-induced aortic contraction in vitro with an IC50 value of 64 μg/mL.268 In addition, butylidene phthalide proved to be active in inhibiting rat uterine contractions induced by prostaglandin F2, oxytocin, and acetylcholine and relaxed

357

Superorder Asteranae Takht., 1967

i­solated guinea pig ileum challenged with acetylcholine, K+, and Ca2+.269 Ligustilide, significantly inhibited the enzymatic activity of nuclear factor-kappa B luciferase activity of murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides and interferon gamma.270 The analgesic property of the plant is validated: the roots of the plant contain the polyynes falcarinol, falcarindiol, and falcarinolone that exhibited analgesic properties in the acetic acid-induced abdominal writhing experiment.271 Furthermore, ligustilide exhibited anti-inflammatory and analgesic properties in the acetic acid-induced abdominal writhing experiment and the formalin experiment.272 Note that ligustilide is a neuroprotector.273 HO

H

H2C

CH3 Falcarinol

Bioresource: In vitro pharmacological study of ligustilide for its effect on neurodegeneration. Falcarindiol is found in Angelica dahurica (Fisch.) Benth. & Hook. f., discussed next. 9.3.2.1.2  Angelica dahurica (Fisch.) Benth. & Hook. f. [From Latin angelica = referring to the medicinal properties of the plant that are said to have been revealed to a monk by an angel who told him it was a cure for malarial fever, and dahurica, from the Mongolian Daur people] History: This plant was first formally described in Genera Plantarum Umbelliferarum by Georg Franz Hoffmann in 1816. Hoffmann (1760–1826) was a German botanist. Common names: Dahurian angelica, bai zhi (Chinese), byakushi (Japanese), gu rit dae (Korean). Basionym: Callisace dahurica Fisch. Habitat: It is a stout perennial herb found in the grasslands of China, Taiwan, Japan, Korea, and Russia. Diagnosis: This plant grows to a height of 3 m. The root is carrot-shaped, brown, 5 cm thick, and strongly aromatic. The stems are purplish green, 5 cm thick, ribbed, and hairy. The basal and lower leaves have long petioles. The sheaths are oblong and glabrous. The blade is triangular, 30 cm × 25 cm to 50 cm × 35 cm, and pinnate. The leaflets are sessile, oblong, 4 cm × 1 cm to 10 cm × 4.5 cm, decurrent at the base, and acute at the apex. The umbels are 30 cm wide. The peduncles are 5–25 cm long and scabrous. The rays are numerous and hairy. The bracteoles are numerous and lanceolate. The petals are white, ovate, and retuse. The fruits are globose and 0.7 cm in diameter (Figure 9.34). Medicinal uses: In Mongolia, this plant is used to treat diphtheria. In China, this plant is used to treat headache, colds, toothache, hematuria, gonorrhea, boils, skin infection, liver diseases, and nose bleeding. In Taiwan, this plant is used to reduce swellings and remove corns from the feet. In Cambodia, Laos, and Vietnam, this plant is used to expel worms from the intestines and to treat diarrhea and skin infection. H

OH CH3

H2C HO

H Falcarindiol

358

Medicinal Plants of China, Korea, and Japan

FIGURE 9.34  Angelica dahurica (Fisch.) Benth. & Hook. f.

Pharmacology: The polyyne falcarindiol isolated from the roots of Angelica dahurica (Fisch.) Benth. & Hook. f. compromised the survival of methicillin-resistant Staphylococcus aureus cultured in vitro and may account for the antibacterial (diphtheria) property of the plant.274 Besides, the plant contains series of furanocoumarins of pharmacological interest such as imperatorin and byakangelicin. Imperatorin and byakangelicin protected cultured human hepatocellular liver carcinoma (HepG2) cells against tacrine-induced cellular damage with IC50 values of about 36.6 and 47.9 μM, hence the use of the plant to treat liver diseases.275 The anti-inflammatory property of Angelica dahurica (Fisch.) Benth. & Hook. f. is confirmed: imperatorin inhibited prostaglandin E2 generation by rat peritoneal macrophages stimulated with bacterial lipopolysaccharides.276 Another anti-inflammatory coumarin found in the plant is byakangelicol that inhibited interleukin-1b-induced prostaglandin E2 production in human lung adenocarcinoma epithelial (A549) cells cultured in vitro.277 Besides, a coumarin isolated from the plant inhibited the enzymatic activity of cyclooxygenase-2 in bone marrow-derived mast cells cultured in vitro.278

O

O O

H3C CH3 Imperatorin

O

359

Superorder Asteranae Takht., 1967 OCH3

O

O

OCH3

O

O CH3 O

CH3

Byakangelicol



O

O

O

OH 9-Hydroxy-4-methoxypsoralen



In addition, 9-hydroxy-4-methoxypsoralen and alloisoimperatorin showed potent antioxidant effects in the 2,2-diphenyl-1-picrylhydrazyl experiment.279 Imperatorin induced vasodilation of mouse thoracic aorta and may account for the use of the plant to alleviate headache.280 Furthermore, imperatorin significantly inhibited the synthesis of tyrosinase in mouse melanoma (B16) cells and inhibited the enzymatic activity of beta-secretase.281,282 Moreover, 9-hydroxy-4-methoxypsoralen extracted from the roots inhibited the enzymatic activity of tyrosinase.283 The coumarin pangelin extracted from the plant abrogated the survival of mouse lymphocytic leukemia (L1210), human promyelocytic leukemia (HL-60), human erythromyeloblastoid leukemia (K562), and murine melanoma (B16F10) cells cultured in vitro, and imperatorin was found to induce apoptosis in human promyelocytic leukemia (HL-60) cells cultured in vitro.284,285

CH3 H3C O HO

O

O

O

O

H2N O

Gamma amino butyric acid

CH3 Phellopterin

Finally, imperatorin and falcarindiol were able to increase the levels of gamma amino butyric acid in the central nervous system via inhibition of gamma amino butyric acid catabolism.286 Note that phellopterin isolated from this plant is a benzodiazepine receptor partial agonist in vitro.287 Bioresource: In vitro pharmacological study of phellopterin for its effect on anxiety. Coumarins are found in Angelica decursiva (Miq.) Franch. & Sav., discussed next.

360

Medicinal Plants of China, Korea, and Japan

9.3.2.1.3  Angelica decursiva (Miq.) Franch. & Sav. [From Latin angelica = referring to the medicinal properties of the plant that are said to have been revealed to a monk by an angel who told him it was a cure for malarial fever, and decursiva = decurrent] History: This plant was first formally described in Annales Museum Botanicum LugdunoBatavi by Friedrich Anton Wilhelm Miquel in 1867. Miquel (1811–1871) was a Dutch botanist. Common names: Zi hua qian hu (Chinese), nodake (Japanese), ba di na mul (Korean). Basionym: Porphyroscias decursiva Miq. Synonyms: Ligusticum melanotilingia (H. Boissieu) Kitag., Ostericum melanotilingia (H. Boissieu) Kitag., Peucedanum decursivum (Miq.) Maxim., Peucedanum grandifolioides H. Wolff, Peucedanum melanotilingia (H. Boissieu) H. Boissieu, Peucedanum porphyroscias Makino, Selinum melanotilingia H. Boissieu. Habitat: This stout perennial herb grows along the riverbanks of China, Tibet, Taiwan, Japan, Korea, Russia, and Vietnam. Diagnosis: Angelica decursiva (Miq.) Franch. & Sav. is 2 m tall. The root is brown, conical, 2 cm in diameter, and strongly aromatic. The stems are purple-green, ribbed, and glabrous. The petiole is 10–35 cm long. The sheaths are purple and elliptical. The blade is triangular, 10–25 cm long, and pinnate. The leaflets are ovate, 5 cm × 2 cm to 15 cm × 5 cm, decurrent at the base, and acute at the apex. The peduncles are 3–7.5 cm long and hairy. The bracts are purplish, ovate, sheath-like, and reflexed. The rays are numerous, 3 cm long, and hairy. The bracteoles are linear and greenish purple. The pedicels are hairy. The calyx lobes are triangular. The petals are dark purple and obovate. The anthers are dark purple. The fruits are oblong and 0.5 cm in diameter (Figure 9.35).

FIGURE 9.35  Angelica decursiva (Miq.) Franch. & Sav.

361

Superorder Asteranae Takht., 1967

Medicinal uses: In China, Japan, and Taiwan, the roots are used to treat cough, headache, and bronchitis and to promote menses. In Cambodia, Laos, and Vietnam, the roots are used to treat rheumatism and to assuage neuralgia. Pharmacology: Angelica decursiva (Miq.) Franch. & Sav. contains a pyranocoumarin decursin that abrogated the survival of various human cancer cells achieving ED50 values of about 5–16 μg/mL via protein kinase C activation.288 In addition, decursin extracted from the roots of Angelica gigas Nakai displayed dramatic in vivo antiangiogenic activity.289 Besides, decursin administered intraperitoneally to rodents at 1 and 5 mg/kg body weight significantly improved scopolamine-induced amnesia in them in the Morris water maze experiment. Finally, decursin significantly inhibited the enzymatic activity of acetylcholinesterase in vivo.290 One might be curious to study the plant for analgesic and anti-­ inflammatory properties. O

H3C CH3

O

H3C

O CH3

O

O

Decursin

Bioresource: In vitro pharmacological study of decursin for its effect on Alzheimer’s disease. The next plant discussed in this section is Angelica megaphylla Diels. 9.3.2.1.4  Angelica megaphylla Diels [From Latin angelica = referring to the medicinal properties of the plant that are said to have been revealed to a monk by an angel who told him it was a cure for malarial fever, and Latin megaphylla = with large leaves] History: This plant was first formally described in Botanische Jahrbücher für Systematik, Pflanzengeschichte und Pflanzengeographie by Friedrich Ludwig Emil Diels in 1900. Diels (1874–1945) was a German botanist. Common names: Da ye dang gui (Chinese), cham dang gwi (Korean). Synonym: Peucedanum megaphyllum (Diels) H. Boissieu. Habitat: This robust perennial herb grows in grasslands and on riverbanks and is found in Russia and China. Diagnosis: Angelica megaphylla Diels is 2.5 m tall. The root is conical and brown. The stems are 2 cm thick, thinly ribbed, and glabrous. The petiole is 25 cm long. The sheath is ovate and 2.5–4 cm long. The blade is triangular, 20 cm × 20 cm to 40 cm × 35 cm, and pinnate. The leaflets are oblong, 5 cm × 2 cm to 15 cm × 6 cm, trilobed, serrate, and acuminate at  the apex. The umbels are 10 cm wide. The peduncles are 5–10 cm long and densely hairy. The rays are numerous and densely hairy. The umbellules are densely flowered. The sepals are minute. The petals are purplish and oblong. The fruits are ovoid and 0.6 cm in diameter. Medicinal uses: In China, this plant is used to treat arthritis and to assuage toothache. Pharmacology: The anti-inflammatory property of Angelica megaphylla Diels is confirmed: an extract of the plant inhibited the secretion of nitric oxide by macrophages stimulated with bacterial lipopolysaccharides and interferon gamma.291 One might be curious to look for analgesic agents in this plant.

362

Medicinal Plants of China, Korea, and Japan

Bioresource: Analgesic agent(s). The next plant discussed in this section is Angelica sinensis (Oliv.) Diels. 9.3.2.1.5  Angelica sinensis (Oliv.) Diels. [From Latin angelica = referring to the medicinal properties of the plant that are said to have been revealed to a monk by an angel who told him it was a cure for malarial fever, and sinensis = from China] History: This plant was first formally described in Hooker’s Icones Plantarum by Daniel Oliver in 1891. Oliver (1830–1916) was a British botanist. Common names: Chinese angelica, dang gui (Chinese), toki (Japanese), tanggwi (Korean). Basionym: Angelica polymorpha var. sinensis Oliv. Habitat: This perennial herb grows in the forests of China. Diagnosis: Angelica sinensis (Oliv.) Diels. is 1 m tall. The root is cylindrical, anthropomorphic, and strongly aromatic. The stems are purplish green, ribbed, and branched above. The basal and lower petiole is 4.5–20 cm long. The sheaths are purplish green and ovate. The blade is 10 cm × 12 cm to 30 cm × 25 cm, pinnate, and displays 3–4 pairs of pinnae.  The leaflets are ovate, 2 cm × 0.7 cm to 3.5 cm × 2 cm, trilobed, and serrate. The peduncles are 8–20 cm long. The rays are numerous, unequal, and scabrous. The bracteoles are linear and 0.5 cm long. The umbellules are densely flowered. The pedicels are slender and 3 cm long in fruits. The calyx lobes are minute. The petals are white. The fruits are elliptical and 0.5 cm in diameter (Figure 9.36). Medicinal uses: In Korea, this plant is used to treat urogenotal diseases, colds, and fever. In China, this plant is used to stimulate the circulation of blood, to cure fatigue, to regulate

FIGURE 9.36  Angelica sinensis (Oliv.) Diels.

363

Superorder Asteranae Takht., 1967

menses, and to check hemoptysis and hemorrhages. It is also used to excite the discharge of urine, to contract the uterus, and as a sedative. Pharmacology: This herb has been used in traditional Chinese medicine and is approved by State Drugs Administration of China as a drug for treatment of cardiovascular and cerebrovascular diseases.292 This plant contains paeoniflorin that promoted the increase of hematopoietic progenitor cells in bone marrow of radiated rodents.293 Besides, ligustilide from this plant inhibited the aggregation of platelets induced by adenosine diphosphate in rodents.294 The plant is cytotoxic on probable account of butylidene phthalide and ligustilide: extracts of the plant compromised the multiplication of human lung adenocarcinoma epithelial (A549), human colon cancer (HT29), and human glioma (DBTRG-05MG) cells cultured in vitro, via apoptosis induction.295,296 Ligustilide was dramatically cytotoxic against mouse lymphocytic leukemia (L1210) and human erythromyeloblastoid leukemia (K562) cells achieving IC50 values of 2.2 and 4.7 μM, respectively.297 Butylidene phthalide suppressed growth of the human glioblastoma multiforme (DBTRG-05MG) and rat glioma RG2 cells cultured in vitro.298 The plant is anxiolytic: the essential oil extracted from this plant displayed anxiolytic effects in the stress-induced hyperthermia experiment.299 p-Hydroxyphenethyl trans-ferulate, butylidene phthalide, falcarindiol, and imperatonin isolated from the roots exhibited affinity toward serotonin receptors.300 In addition, gelispirolide and riligustilide, two phthalides isolated from this plant, showed some affinity for the gamma amino butyric acid receptor with IC50 values of 29 and 24 μM, respectively.301 Besides, ligustilide exhibited antioxidant and antiapoptotic properties and protected rat pheochromocytoma (PC12) cells against H2O2 damages.302,303 Falcarindiol isolated from the roots inhibited the growth of Mycobacterium tuberculosis cultured in vitro.304 Finally, ferulic acid isolated from Angelica sinensis (Oliv.) Diels protected rodents against acetaminophen-induced hepatocellular damage.305 H3CO HO

O OH Ferulic acid

Bioresource: In vitro pharmacological study of ligustilide for its effect on neurodegeneration. The next plant discussed in this section is Angelica sylvestris L. 9.3.2.1.6  Angelica sylvestris L. [From Latin angelica = referring to the medicinal properties of the plant that are said to have been revealed to a monk by an angel who told him it was a cure for malarial fever, and Latin sylvestris = growing in woods] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Wild angelica, lin dang gui (Chinese), gae gu rit dae (Korean). Habitat: It is a perennial herb found in grassy spots in the forests of Russia, China, Nepal, and Northern Europe. Diagnosis: Angelica sylvestris L. is 2.5 m tall. The root is conical, thick, and slightly aromatic. The stems are 2.5 cm in diameter, ribbed, and hairy. The basal and lower leaves are

364

Medicinal Plants of China, Korea, and Japan

FIGURE 9.37  Angelica sylvestris L.

petiolate. The petiole is long. The sheaths are ovate. The blade is broadly triangular and pinnate. The leaflets are sessile, lanceolate to ovate, 2.5 cm × 1 cm to 7.5 cm × 3.5 cm, cuneate at the base, and serrate. The umbels are 15 cm wide. The rays are numerous and hairy. The bracteoles are numerous, linear, and as long as the pedicels. The sepals are inconspicuous. The petals are pure white and ovate. The fruits are ovoid and 0.6 cm in diameter (Figure 9.37). Medicinal uses: In China, this plant is used to treat numbness, cramps, arthritis, rheumatism, headache, and swollen feet. In Cambodia, Laos, and Vietnam, this plant is used to treat headache, fever, liver, kidney, and spinal diseases and as a sedative. Constituents: Angelica sylvestris L. contains series of coumarins including imperatonin, aviprin, byakangelicin, xanthotoxol and umbelliprenin.306 Pharmacology: Note that the anti-inflammatory property of the plant could involve coumarins: imperatorin inhibited prostaglandin E2 generation by rat peritoneal macrophages stimulated with bacterial lipopolysaccharides.276 Besides, xanthotoxol protected rat erythrocytes against free radicals-induced cellular damage.307 Imperatorin and byakangelicin isolated from Angelica dahurica (Fisch.) Benth. & Hook. f. protected human hepatocellular liver carcinoma (HepG2) cells against tacrine-induced cellular damage with EC50 values of about 36.6 and 47.9 μM, respectively.275 Byakangelicin ­protected rodents against sepsis induced by bacterial lipopolysaccharides and d-galactosamine.308 Xanthotoxol induced the vasodilation of guinea pig atria by a mechanism involving calcium channels, hence the use of the plant in treating dizziness and headache that are both symptoms of hypertension.309 Xanthotoxol exhibited sedative activity in dogs, cats, and rodents.310

365

Superorder Asteranae Takht., 1967 OCH3

O

O

O

O CH3

HO CH3 Byakangelicin



OH Xanthotoxol



O

H3C CH3

CH3

O

O

O

O

O

O

CH3 Umbelliprenin

Another interesting coumarin in this plant is umbelliprenin that protected rodents against the formation of papillomas induced by 12-O-tetradecanoylphorbol-13-acetate.311 Bioresource: In vitro pharmacological study of xanthotoxol for its effect on alopecia. The next plant discussed in this section is Bupleurum chinense DC. 9.3.2.1.7  Bupleurum chinense DC. [From Greek bous = ox, and pleuron = a rib, and from Latin chinense = from China] History: This plant was first formally described in Prodromus Systematis Naturalis Regni Vegetabilis by Augustin Pyramus de Candolle in 1830. de Candolle (1778–1841) was a Swiss botanist. Common names: Bupleurum, bee chia hu (Chinese), saiko (Japanese), si ho (Korean). Synonyms: Bupleurum chinense var. vanheurckii (Müll. Arg.) Shan & Yin Li, Bupleurum chinense Franch., Bupleurum falcatum var. ensifolium H. Wolff, Bupleurum togasii Kitag., Bupleurum vanheurckii Müll. Arg. Habitat: It is a perennial herb found in the grasslands of China, India, Japan, Korea, and Taiwan. Diagnosis: Bupleurum chinense DC. is 90 cm tall. The root is stout, elongate, brown, woody, and branched. The stems are zigzag-shaped. The basal leaves are oblanceolate, 4 cm × 0.5 cm to 7 cm × 0.8 cm, tapering at the base, and acuminate at the apex. The middle leaves are elliptical, 4 cm × 1.5 cm to 10 cm × 1.8 cm, with 7–9 nerves, glaucous below, and acute at the apex. The apical leaves are small. The umbels are 5 cm wide. The peduncles are slender and spreading. The bracts are 0.5 cm × 0.1 cm. The rays are slender, 3 cm long, and unequal. The bracteoles are lanceolate and 0.3 cm long. The umbellules are 0.5 cm in diameter and have 5–10 flowers. The petals are bright yellow. The fruits are oblong, brown, and 0.3 cm in diameter (Figure 9.38). Medicinal uses: In China, this plant is used to treat gout and inflammation. In Korea, China, Japan, India, and Taiwan, this plant is used to break malarial fever and to treat bitter mouth, deafness, vertigo, irregular menses, diarrhea, rheumatism, lung diseases, jaundice, liver disease, and indigestion.

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Medicinal Plants of China, Korea, and Japan

FIGURE 9.38  Bupleurum chinense DC.

Constituents: Bupleurum chinense DC. is known to contain triterpene saponins such as saikosaponin v-1, 6″-O-acetyl-saikosaponin b2, 6″-O-acetyl-saikosaponin d, and saikosaponin a and d.312,313 Pharmacology: The hepatoprotective property of this plant is confirmed: an extract of the plant protected rodents against CCl4-induced hepatocellular damage on probable account of saikosaponin a.314,315 The use of the plant to treat dysmenorrhea could be owed to saikosaponin d that is known to be estrogenic. Note that saikosaponin d extracted from Bupleurum falcatum L. has a somewhat similar chemical structure to that of estradiol and induced the multiplication of human breast adenocarcinoma (MCF-7) cells in vitro.316 H3C

CH3

CH3 CH3

OH

OH

O CH3

CH3 O

OH

CH3

O

O

OH HO

H3C

OH

O OH

OH OH Saikosaponin d

Estradiol

OH

Superorder Asteranae Takht., 1967

367

The anti-inflammatory property of the plant may involve saikosaponin a: saikosaponin a isolated from Bupleurum falcatum L. significantly inhibited the proliferation and activation of T lymphocytes stimulated with concanavalin A.317 Finally, saikosaponins inhibited the increase of glutamate in the hippocampus of rodents.318 One might be curious to study the antiplasmodial property of the plant. Bioresource: In vitro pharmacological study of saikosaponin d for its effect on postmenauposal discomfort. The next plant discussed in this section is Cnidium monnieri (L.) Cusson. 9.3.2.1.8  Cnidium monnieri (L.) Cusson [From Greek knide = nettle, and after Louis Guillaume le Monnier (1717–1799), royal physician to Louis XV] History: This plant was first formally described in Centuria I. Plantarum by Carl Linnaeus in 1755. Linnaeus (1707–1778) was a Swedish botanist. Common names: Monnier’s snowparsley, she chuang (Chinese), jashoshi (Japanese), beol sa sang ja (Korean). Basionym: Selinum monnieri L. Habitat: It is an annual herb found in the riparian grasslands of China, India, Korea, Laos, Mongolia, Russia, Vietnam, Europe, and North America. Diagnosis: Cnidium monnieri (L.) Cusson is 65 cm tall. The root is slender. The stems are striate and scabrous. The petiole is 3–10 cm long. The blade is lanceolate, 3 cm × 2 cm to 10 cm × 5 cm, and pinnate. The umbels are 2.5 cm wide. The bracts are linear, 0.2 cm long, and persistent. The rays are 2 cm long and unequal. The bracteoles are linear. The umbellules are densely flowered. The pedicels are 0.5 cm long. The sepals are inconspicuous. The fruits are ovoid and 0.3 cm in diameter (Figure 9.39).

FIGURE 9.39  Cnidium monnieri (L.) Cusson.

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Medicinal Plants of China, Korea, and Japan

Medicinal uses: In China, the fruits are used to cure fatigue, to excite the discharge of urine, to induce menses, and to treat rheumatism, kidney diseases, indigestion, dysentery, urogenital infection, hemorrhoids, and skin diseases. The plant is also used as a sedative. Constituents: Cnidium monnieri (L.) Cusson contains series of coumarins including bergapten, osthol, and imperatorin.319 Pharmacology: Imperatonin probably accounts for the anxiolytic property mentioned above as it is able to inhibit the enzymatic activity of gamma amino butyric acid-transaminase.286 The anti-inflammatory property of the plant is confirmed: extracts of the plant protected rodents against bronchial asthma induced by the inhalation of histamine and exhibited antipruritogenic effect in the substance P-induced itching experiment.320,321 The active coumarin involved here could be osthol that inhibited 2, 4-dinitrofluorobenzeneinduced contact dermatitis and compound 48/80-induced scratching behavior in rodents.322,323 In addition, osthol showed estrogenic property in ovariectomized rodents and may account for the use of the plant to regulate menses.324 Osthol increased androgen, gonadotropin, and nitric oxide synthase activity in immature castrated male rodents.325 Furthermore, osthol mitigated the memory impairment of rodents poisoned with aluminum.326 Note that osthol protected cultured cortical neurons oxygen and glucose deprivation.327 H3C CH3 H

O

O

CH3

O

H3CO H3C

O

CH3 O H3C

O H3C

CH3



O

Osthol



CH3

Torilin

Osthol showed remarkable cytotoxic activities against human promyelocytic leukemia (HL-60), human epithelial cervical cancer (Hela), human colon adenocarcinoma (CoLo 205), and murine macrophage-like (P-388 D1) cells cultured in vitro.328,329 Finally, osthol lowered the glycemia of diabetic rodents and abrogated the growth of Mycobacterium tuberculosis cultured in vitro with a minimum inhibitory concentration of 32 μg/mL.330,331 Note that the sesquiterpenes torilin and torilolone isolated from Cnidium monnieri (L.) Cusson protected human hepatocellular liver carcinoma (HepG2) cells against tacrine-induced cellular damage.332 Bioresource: In vitro pharmacological study of osthol for its effect on tuberculosis. The next plant discussed in this section is Glehnia littoralis F. Schmidt ex Miq. 9.3.2.1.9  Glehnia littoralis F. Schmidt ex Miq. [After Peter von Glehn (1835–1876), a Russian botanist and plant explorer in Baltic Russia, and from Latin littoralis = of the seashore] History: This plant was first formally described in Annales Museum Botanicum LugdunoBatavi by Friedrich Schmidt in 1867. Schmidt (1832–1908) was a Russian botanist.

Superorder Asteranae Takht., 1967

369

Common names: Beach silvertop, shan hu cai (Chinese), hamaboufu (Japanese), gaet bang pung (Korean). Synonym: Phellopterus littoralis (F. Schmidt ex Miq.) Benth. Habitat: It is a creeping herb found in sandy beaches and sandy soils of China, Taiwan, Japan, Korea, and Russia. Diagnosis: Glehnia littoralis F. Schmidt ex Miq. is 75 cm tall. The root is elongate, cylindrical, 30 cm × 0.5 cm to 70 cm × 1.5 cm, and yellowish white. The young flower buds and leaves are edible. The stems are reddish. The basal and lower leaves are long petiolate. The petiole is 5–15 cm long. The blade is ovate and pinnate. The ultimate segments are oblong, 1 cm × 0.7 cm to 5 cm × 3.5 cm, serrate, and obtuse at the apex. The umbels are 3–6 cm in diameter. The peduncles are 5 cm long, hairy, and fleshy. The rays are 3 cm long and fleshy. The bracteoles are linear. The pedicels are numerous and fleshy. The flowers are small and yellowish. The stamens are conspicuous. The fruits are 1 cm in diameter, fleshy, yellowish red, and hairy (Figure 9.40). Medicinal uses: In Korea, this plant is used to treat colds. In China, this plant is used to treat tuberculosis. The roots are used to produce sweating, to break fever, and to mitigate pain. Constituents: The plant contains an essential oil with alpha-pinene, limonene, beta-phellandrene, germacrene B, spathulenol, beta-oplopenone, panaxynol, propyl octanoate, hexadecanoic acid, linoleic acid, and lignans.333,334 Pharmacology: Glehnia littoralis F. Schmidt ex Miq. contains series of polyynes that showed antibacterial and antifungal properties in vitro.335 Are polyynes responsible for the antimycobacterial properties of the plant? Other polyynes of interest isolated from Glehnia littoralis F. Schmidt ex Miq. are falcaindiol and falcarinol that abrogated the proliferation of human cancer cells.336

FIGURE 9.40  Glehnia littoralis F. Schmidt ex Miq. (From Coll.: G. Murata and H. Koyama. Plantae Japonicae Exsiccatae. No. 432. Ex Herbario Universitatis Kyotoensis. Loc.: Japan, Honshu, Pref. Kyoto (Prov. Tango): Hakoishi, Kumihama-cho, Kumano-gun, on sandy coast. Date: June 26, 1965.)

370

Medicinal Plants of China, Korea, and Japan H2C

OH CH3

HO Falcaindiol

In addition, falcarindiol was remarkably cytotoxic against human colon cancer (HT-29) cells cultured in vitro achieving an IC50 value of 35 μM.337 Note that falcarinol was analgesic in the acetic acid-induced abdominal writhing experiment, hence the analgesic property of the plant.271 With regard to the possible anti-inflammatory property of Glehnia littoralis F. Schmidt ex Miq., an extract of the plant strongly inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor-alpha and interleukin-1b by murine macrophages (RAW264.7) stimulated with bacterial lipopolysaccharides338 The active agent involved here is yet to be characterized, but one could reasonably think of some coumarins or flavonoids as Glehnia littoralis F. Schmidt ex Miq. is known to contain quercetin, isoquercetin, rutin, chlorogenic acid, and caffeic acid that showed antioxidant effects in the 2,2-diphenyl-1-picrylhydrazyl experiment.339 Bioresource: In vitro pharmacological study of falcarindiol for its effect on colon cancer. Oenanthe javanica (Blume) DC. is examined next. 9.3.2.1.10  Oenanthe javanica (Blume) DC. [From Greek oinos = wine, and anthos = flower, and from Latin javanica = from Java] History: This plant was first formally described in Bijdragen tot de Flora van Nederlandsch Indië of Karl Ludwig von Blume in 1826. Blume (1796–1862) was deputy director of agriculture in Bogor.

FIGURE 9.41  Oenanthe javanica (Blume) DC. (From Coll.: W. Meijer. Flora of Sabah. Herbarium of the Forest Department Sandakan. No. 141635. Loc.: Malaysia, Sabah, Nalumad, above Mokodu river. Alt.: 500 m. Date: July 19, 1994.)

371

Superorder Asteranae Takht., 1967

Common names: Japanese parsley, Chinese celery, dropwort, kangkong cina (Malay), shui qin (Chinese), seri (Japanese), mi na ri (Korean). Basionym: Sium javanicum Blume. Synonym: Oenanthe decumbens Koso-Pol. Habitat: This little perennial herb is found wild in watery spots or is cultivated as a vegetable in China, India, Indonesia, Japan, Korea, Laos, Malaysia, Burma, Nepal, New Guinea, Pakistan, the Philippines, Russia, Thailand, Australia and Vietnam. Diagnosis: Oenanthe javanica (Blume) DC. is 50 cm tall and sweet-scented. The root is fibrous. The stems are slender, decumbent, and fleshy. The basal petiole is 5–10 cm long. The blade is oblong and pinnate. The segments at the apex are ovate, 0.5 cm × 0.5 cm to 5 cm × 2.5 cm, and serrate. The cauline leaves are sessile. The umbels are 5 cm wide. The peduncles are 2–15 cm long. The bracts are linear and 1.1 cm long. The rays are 3 cm long. The bracteoles are linear and 2 4 cm long. The umbellules are densely flowered. The pedicels are 0.4 cm long. The petals are white. The sepals are minute. The fruits are globose and 0.2 cm in diameter (Figure 9.41). Medicinal uses: In China, this plant is used to heal abscesses, dog bites, and cancerous swellings. It is also used to break fever and to treat colds, kidney diseases, and hepatitis. In Cambodia, Laos, and Vietnam, this plant is used to excite the discharge of urine and to treat indigestion. OH HO

O O O OH

O Persicarin

S

OCH3 OH

O

Pharmacology: Oenanthe javanica (Blume) DC. contains a sulfated flavonoid persicarin that inhibited bromobenzene-induced hepatocellular lipid peroxidation and significantly protected the primary cultures of rat cortical neurons against glutamate-induced cellular damage.340,341 An extract of the plant protected rodents against ethanol-induced hepatic damage.342 Besides, a total phenolic extract of the plant inhibited the replication of the hepatitis B virus cultured in vitro.343 In addition, a flavone isolated from Oenanthe javanica (Bl.) given at doses of 200 and 400 mg/kg daily for 10 days lowered the glycemia and stimulated the secretion of insulin in alloxan-induced diabetic rodents.344

OH

H3C OH Oenanthotoxin

Note that members of the genus Oenanthe L. are known to synthesize series of polyynes of which cicutoxin and oenanthotoxin act as gamma-amino butyric acid antagonists in the central nervous system. One of these plants is Oenanthe crocata L. that was used in pre-Roman Sardinia for the ritual killing of elderly people. In fact, ingestion of large amounts of Oenanthe crocata L. is

372

Medicinal Plants of China, Korea, and Japan

quickly followed by nausea, vomiting, diarrhea, a strange rictus grin (Sardonic grin), tachycardia, mydriasis, rhabdomyolysis, renal failure, coma, respiratory impairment, cardiac dysrhythmias, and lethal seizures.345 Surprisingly, an injection of 3 mL/kg of an extract of Oenanthe javanica (Blume) DC. significantly corrected the arrhythmias induced by aconitine and barium chloride and lowered the rates of ventricular fibrillation induced by calcium chloride.346 Bioresource: In vitro pharmacological study of persicarin for its effect on neurodegeneration. The next plant discussed in this section is Sanicula coerulescens Franch. 9.3.2.1.11  Sanicula coerulescens Franch. [From Latin sanicula = diminutive of the Latin word sanare meaning “to heal,” and coerulescens = bluish] History: This plant was first formally described in Bulletin de la Societe Philomatique de Paris by Adrien René Franchet in 1894. Franchet (1834–1900) was a French botanist. Common names: Blue sanicle, tian lan bian dou cai (Chinese). Synonyms: Sanicula dielsiana H. Wolff, Sanicula erythrophylla Bobrov, Sanicula stapfiana H. Wolff. Habitat: This little herb is found in the forests and watery spots of China. It is cultivated as an ornamental plant. Diagnosis: Sanicula coerulescens Franch. is 35 cm tall. The root is slender and fibrous. The stems are erect, fleshy, and dark brown. The basal leaves are numerous. The petiole is purplish and 5–15 cm long. The blade is cordate, 3 cm × 5 cm to 7 cm × 10 cm, and palmately lobed. The central lobe is ovate, 3 cm × 1.5 cm to 7 cm × 5 cm, cuneate at the base, and shallowly trilobed at the apex. The lateral lobes are oblique, bilobed, purplish below, and crenate. The inflorescence is a lax raceme of light blue flowers. The bracts are ovate and 0.2 cm long. The rays are 1 cm long. The bracteoles are linear and minute. The sepals are linear and acute. The petals are bluish purple. The styles are 0.2 cm long and recurved. The fruits are globose, 0.2 cm in diameter, and covered with tiny spines (Figure 9.42). Medicinal use: In China, this plant is reduced to a paste that is applied to malignant sores. Constituents: Apparently unknown. Members of the genus Sanicula L. are known to accumulate high amounts of rosmarinic acid.347 Pharmacology: Rosmarinic acid is anti-inflammatory and may be responsible for the healing and anticancer properties of Sanicula coerulescens Franch. listed above.348 Note that rosmarinic acid inhibited the migration of human breast adenocarcinoma parental (MDAMB-231BO) cells.349 Other possible cytotoxic agents in this plant could be some oleanane triterpene saponins such assaniculasaponins I–XI that were isolated from Sanicula elata Ham. var. chinensis Makino.350 O HO

H

COOH

O

OH

OH

HO Rosmarinic acid

Sanicula coerulescens Franch. is probably antioxidant as an extract of Sanicula graveolens Poepp. ex DC. showed a noteworthy antioxidant effect in the 2,2-diphenyl-1-picryl-hydrazyl experiment.351 This effect could be mediated by rosmarinic acid or 3′-O-beta-d-glucopyranosyl rosmarinic acid that has been isolated from Sanicula europeae L.352

Superorder Asteranae Takht., 1967

373

FIGURE 9.42  Sanicula coerulescens Franch.

A fraction obtained from Sanicula europaea L. abrogated the replication of the human parainfluenza virus cultured in vitro on probable account of rosmarinic acid, as rosmarinic acid isolated from Sanicula europaea L. abrogated the survival of the human immunodeficiency virus and improved the survival of rodents infected with the Japanese encephalitis virus.353−355 Bioresource: In vitro pharmacological study of rosmarinic acid for its effect on cancer. The next plant discussed in this section is Torilis japonica (Houtt.) DC. 9.3.2.1.12  Torilis japonica (Houtt.) DC. [From Latin torilis = obscure, and japonica = from Japan] History: This plant was first formally described in Natuurlijke Historie by Maarten Houttuyn in 1777. Houttuyn (1720–1798) was a Dutch botanist. Common names: Upright hedge-parsley, Japanese hedge-parsley, xiao qie yi (Chinese), yabujirami (Japanese), sa sang ja (Korean). Basionym: Caucalis japonica Houtt. Synonyms: Caucalis praetermissa (Hance) Franch., Tordylium anthriscus L., Torilis anthriscus (L.) C.C. Gmel., Torilis anthriscus var. japonica (Houtt.) H. Boissieu, Torilis praetermissa Hance. Habitat: This slender herb is widespread throughout the grasslands and forests of the northern hemisphere. Diagnosis: Torilis japonica (Houtt.) DC. 1 m tall. The basal and lower cauline leaves are petiolate. The petiole is 1.5–10 cm long. The blade is triangular and 20 cm × 15 cm. The pinnae are ovate and 2 cm × 1 cm to 5 cm × 2.5 cm. The peduncles are 2.5–25 cm long

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Medicinal Plants of China, Korea, and Japan

FIGURE 9.43  Torilis japonica (Houtt.) DC. (From Coll.: R.D. Thomas & J. Grey. Herbarium of Northest Louisiana State College, Monroe. Flora of Arkansas. No. 9189. Loc.: Izard County, USA. Date: June 25, 1968.)

and hispid. The bracts are linear. The rays are 3 cm long, spreading, and bristly. The bracteoles are linear and 0.1–0.7 cm long. The umbellules have 4–12 flowers. The pedicels are 0.1–0.4 cm long. The sepals are small and deltoid. The petals are white. The fruits are purple, globose, hairy, and 0.5 cm × 0.2 cm (Figure 9.43). Medicinal uses: In Korea, this plant is used to treat cough, fatigue, hemorrhoids, dysentery, gonorrhea, and skin infection. In China and Japan, this plant is used to break fever, to heal hemorrhoids, and to check intestinal hemorrhages. Pharmacology: Torilis japonica (Houtt.) DC. contains the guaiane-type sesquiterpene torilin that boosted the cytotoxic potencies of adriamycin, vinblastine, taxol, and colchicine against multidrug-resistant human nasopharyngeal carcinoma (KB-V1) and human breast adenocarcinoma (MCF7/ADR) cells cultured in vitro.356 Moreover, torilin, 1-betahydroxytorilin and 1-alpha-hydroxytorilin extracted from the plant were cytotoxic against human lung adenocarcinoma epithelial (A549), human ovary adenocarcinoma (SK-OV-3), human skin melanoma (SK-MEL-2) and human colorectal adenocarcinoma (HCT-15) cells cultured in vitro.357 In addition, torilin impaired neovascularization of chick embryos in the chorioallantoic membrane vascular experiment and completely blocked intravasation of human fibrosarcoma (HT1080) cells in chick embryos.358,359 Besides, torilin inhibited the enzymatic activity of testosterone 5-alpha-reductase and abrogated the survival of Bacillus subtilis.360,361 Finally, torilin inhibited the generation of melanin by mouse melanoma (B16) cells stimulated with alpha-melanocyte stimulating hormone.362 Bioresource: In vitro pharmacological study of torilin for its effect on cancer. The next plant in this section is Trachyspermum ammi (L.) Sprague.

Superorder Asteranae Takht., 1967

375

9.3.2.1.13  Trachyspermum ammi (L.) Sprague [From Latin trachyspermum = rough seeds, and from the Greek ammos = sand] History: This plant was first formally described in Species Plantarum by Carl Linnaeus in 1753. Linnaeus (1707–1778) was a Swedish botanist. Common names: Ajowan caraway, xi ye cao guo qin (Chinese). Basionym: Sison ammi L. Synonyms: Ammi copticum L., Bunium copticum (L.) Spreng., Carum copticum (L.) C.B. Clarke, Daucus copticus (L.) Pers., Ptychotis coptica (L.) DC., Trachyspermum copticum (L.) Link. Habitat: This annual herb grows in the open lands of India, China, the Philippines, and Africa.It is cultivated for its aromatic fruits that are eaten and used to make perfume. Diagnosis: Trachyspermum ammi (L.) Sprague is 40 cm tall. The petiole is 1–5 cm long. The blade is triangular, 2 cm × 2 cm to 8 cm × 5 cm, and pinnate. The segments are filiform and 1.5 cm long. The umbels are 2.5–5 cm in diameter. The bracts are linear and 0.5– 0.7 cm long. The rays are 1–3 cm long. The bracteoles are linear and 0.2 cm long. The umbellules are 1 cm wide and densely flowered. The pedicels are 0.4 cm long. The sepals are conspicuous and minute. The petals are minute and white. The fruits are minute and densely grooved (Figure 9.44). Medicinal uses: In China, the seeds are used to treat spasms, fatigue, pain, indigestion, sore throat, cough, and rheumatism.

FIGURE 9.44  Trachyspermum ammi (L.) Sprague. (From Coll.: D. Merrill. Flora of the Philippines. Herbarium of the Bureau of Science. Loc.: Philippines, cultivated, Manila, Luzon. Date: June 1917.)

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Medicinal Plants of China, Korea, and Japan

Pharmacology: The essential oil of Trachyspermum ammi (L.) Sprague exhibited a broad spectrum of antibacterial and antifungal activities on probable account of thymol and carvacrol that are carminative.363−365 Besides, the spasmolityc and hepatoprotective properties of Trachyspermum ammi (L.) Sprague are confirmed as thymol was found to possess an agonistic effect on alpha1-, alpha2-, and beta-adrenoceptors of smooth muscle preparation.366 In addition, an extract of seeds inhibited the contractions of isolated aorta and jejunum preparations caused by K+, blocked the constriction of trachea caused by carbachol and K+, and protected rodents against acetaminophen and CCl4-induced hepatocellular damage.367 Furthermore, an extract of seeds displayed muscarinic effects on isolated duodenum, ileum, and jejunum of rodents because of acetylcholine.368 The anti-inflammatory and antitussive properties of Trachyspermum ammi (L.) Sprague are validated: an extract of fruits showed a noteworthy antioxidant effect in the 2,2-diphenyl-1-picrylhydrazyl experiment.369 An extract of the plant impaired the aggregation of platelets induced by arachidonic acid, epinephrine, and collagen.370 Moreover, a decoction of the plant relaxed the airways of asthmatic patients and elicited an antitussive effect in rodents.371,372 CH3

CH3 CH3

OH H3C OH H3C



CH3 Carvacrol

H3C

CH3 Thymol

H3C



N+

CH3

O O Acetylcholine

The analgesic property of Trachyspermum ammi (L.) Sprague is confirmed: an extract of the plant exhibited analgesic activity in the tail flick experiment.373 Finally, an extract of plant inhibited 7,12-dimethylbenz[alpha]anthracene-induced skin papillomagenesis in rodents.374 Bioresource: Anti-inflammatory agent(s). The next clade discussed in this section is the order Dipsacales.

9.3.3  Order Dipsacales Juss. ex Bercht. & J. Presl., 1820 The order Dipsacales consists of three families of flowering plants: the Adoxaceae, Caprifoliaceae, and Dipsacaceae. 9.3.3.1  Family Dipsacaceae Juss., 1789, nom. cons., the Teasel Family The family Dipsacaceae consists of 10 genera and about 270 species of rough herbs commonly producing iridoids, saponins, monoterpenoid alkaloids, and alpha-naphthaphenanthridine alkaloids. The leaves are opposite, simple, entire or toothed to deeply pinnatifid, and without stipules. The flowers are grouped into dense, cymose, involucrate heads. The calyx is small and cupulate, or lobed into 4–10 segments. The corolla is tubular, irregular, and has 5 lobes. The corolla lobes are imbricate. The androecium comprises 4 stamens that are arranged alternate to the lobes. The anthers are tetrasporangiate, dithecal, and open by longitudinal slits. The gynoecium consists of a pair of carpels united to form a unilocular ovary. The stigma is bilobed. The achenes are enclosed in the persistent calyx. To date, the family Dipsacaceae seems to have been poorly studied for pharmacology. Dipsacus asper Wall. is examined in this section.

Superorder Asteranae Takht., 1967

377

9.3.3.1.1  Dipsacus asper Wall. [From Greek dipso = thirst, and Latin asper = rough] History: This plant was first formally described in A Numerical List of Dried Specimens by Nathaniel Wallich in 1829. Wallich (1786–1854) was a Danish botanist. Common names: Teasel, chuan xu duan (Chinese). Habitat: This rough perennial herb grows in the watery and grassy spots of China, India, and Burma. Diagnosis: Dipsacus asper Wall. is 2 m tall. The root is fusiform, 1.5 cm in diameter and fleshy. The stems are rigid, erect, branched, ridged, and spiny. The basal leaves are rosulate. The petiole is 25 cm long. The blade is pinnatisect, 15 cm × 5 cm to 25 cm × 20 cm, and spiny. The lower cauline leaves are pinnatifid. The terminal segment is lanceolate, 10 cm × 5 cm, serrate, and acuminate at the apex. The upper cauline leaves are lanceolate. The flower heads are globose, 1.5–3.5 cm in diameter, and spiny. The peduncles are 50 cm long. The involucral bracts are lanceolate and spiny. The bracts are obovate, 0.5–1 cm long, rostrate, and spiny. The calyx is disc-shaped, minute, and spiny. The corolla is yellowish, infundibular, and 1 cm long. The corolla tube is 0.25 cm long. The corolla lobes are unequal and puberulous. The stamens are exerted. The anthers are purple. The achenes are ovoid and 0.5 cm long (Figure 9.45). Medicinal uses: In China, the roots are used to improve the circulation of blood, to reduce swellings, to relax the uterus, to excite the discharge of urine, to heal wounds and boils, to cure fatigue, to stop diarrhea, to regulate menses, to check hemorrhages, to heal hemorrhoids, and to treat cancer of the breast.

FIGURE 9.45  Dipsacus asper Wall. (From Coll.: W.T. Tsang. Det.: D. Merrill. Flora of Kwangtung. Herbarium Lingnan Natural History Survey and Museum. Lingnan University, Canton, China. No. 20684. Loc.: China, Chong Uen Shan near Kau Fung. Date: February 30, 1932.)

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Medicinal Plants of China, Korea, and Japan

Constituents: Dipsacus asper Wall. produces series of saponins, caffeic acid, 2,6-dihydroxycinnamic acid, vanillic acid, 2′-O-caffeoyl-d-glucopyranoside ester, caffeoylquinic acid, and iridoid glucosides such as loganin, cantleyoside, triplostoside A, lisianthioside, and 6′-O-beta-d-apiofuranosyl sweroside.375,376 Pharmacology: Note that members of the genus Dipsacus have an impressive array of pharmacological activities.377 Dipsacus asper Wall. contains series of saponins exhibiting cardioprotective properties.378 In addition, hederagenin glycosides isolated from the plant were remarkably cytotoxic against mouse lymphocytic leukemia (L1210), human promyelocytic leukemia (HL-60) and human ovary adenocarcinoma (SK-OV-3) cells cultured in vitro achieving IC50 values of 4.7–8.7 μg/mL, probably via apoptosis induction.379,380 Another cytotoxic saponin in this plant is akebia saponin D that abrogated the survival of human histiocytic lymphoma (U937) cells via apoptotic induction.380 Besides, akebia saponin D protected rat pheochromocytoma (PC12) cells against beta amyloid-induced cellular damages.381 The anti-inflammatory property of Dipsacus asper Wall. is probably owed to series of phenolic glycosides of which 3,4-di-O-caffeoylquinic acid, methyl 3,4-di-O-caffeoyl quinate, 3,5-di-O-­ caffeoylquinic acid, methyl 3,5-di-O-caffeoyl quinate, and 4,5-di-O-caffeoylquinic acid showed antioxidant effects in the 2,2-diphenyl-1-picrylhydrazyl experiment.382 3,5-Dicaffeoylquinic acid protected human neuroblastoma (SH-SY5Y) neurons cultured in vitro against H2O2-induced cellular (damage and may account for the cognitive improvement observed in rodents poisoned with aluminum.383,384 The plant contains asperosaponin VI that induced the proliferation, differentiation, and mineralization of preosteoblastic (MC3T3-E1) cells cultured in vitro.385 Bioresource: In vitro pharmacological study of 3,5-dicaffeoylquinic acid for its effect on skin ageing.

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FIGURE 3.2  Eichhornia crassipes (Mart.) Solms.

FIGURE 3.5  Canna indica L.

FIGURE 3.7  Alpinia conchigera Griff.

FIGURE 3.16  Costus speciosus (J. König) Sm.

FIGURE 3.22  Hedychium coronarium J. König.

FIGURE 3.26  Phaeomeria imperialis Lindl.

FIGURE 3.98  Sansevieria trifasciata Prain.

FIGURE 3.102  Zephyranthes carinata Herb.

ALTERNATIVE MEDICINE

Medicinal Plants of China, Korea, and Japan Bioresources for Tomorrow’s Drugs and Cosmetics Asian medicinal plants show great promise in pharmaceutical and cosmetological development. Researchers engaged in the discovery of new leads in these areas need robust conceptual tools and understanding of the interrelated basics of botany, ethnobotany, biomolecular pharmacology, phytochemistry, and medicinal chemistry to guide their investigations. Medicinal Plants of China, Korea, and Japan: Bioresources for Tomorrow’s Drugs and Cosmetics explores the fundamental science and demonstrates the compelling potential of these versatile plants, providing an essential resource to stimulate and guide focused inquiry. It is essential that researchers appreciate the chemotaxonomical statuses of these plants, so chapters are arranged according to the Angiosperm Phylogeny Group system of plant taxonomy. The book discusses the history, synonymy, habitat, description, traditional uses, and pharmacochemistry of each plant. Detailed photographs and hand-made botanical plates enable quick and reliable identification of each plant species. Critical analyses of peer-reviewed articles provide the basis for Bioresource sections in each chapter wherein readers are advised, engaged, and guided toward exciting pharmaceutical and cosmetological research proposals. Also included are indexes of botanical terms, pharmacological terms, natural products, and local names. Detailing 200 medicinal plant species carefully selected for their novelty and pharmacological and cosmetological importance, this volume provides a firm starting point for anyone looking forward to unlocking the potential of Asian medicinal plants. In addition, this invaluable book identifies numerous patentable leads.

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