Medicinal plant research in africa pharmacology and chemistry

1 Monoterpenes and Related Compounds from the Medicinal Plants of Africa Michel Kenne Tchimenea, Christopher O Okunjia,c, Maurice Mmaduakolam Iwua and Victor Kueteb a International Centre for Ethnomedicine and Drug Development, Nsukka, Nigeria, bDepartment of Biochemistry, University of Dschang, Dschang, Cameroon, cUSP Headquarter, Rockville, MD 1.1 Introduction Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16 They are predominantly products of the secondary metabolism of plants, although specialized classes occur in some animals and microorganisms, and are usually isolated from the oils obtained by steam distillation or solvent extraction of leaves, fruits, some heartwoods, and, rarely, roots, and bark [1] In favorable cases they occur to the extent of several percent of the wet weight of the tissue Conjugated nondistillable forms, e.g., terpene-β-D-glucoside, are also frequently found, especially in the floral organs They are the most representative molecules, constituting 90% of the essential oils, and have a great variety of structures Monoterpenes may be linear (acyclic) or they may contain rings Biochemical modifications such as oxidation or rearrangement produce the related monoterpenoids They are known for their many biological activities such as antimicrobial, hypotensive, antiinflammatory, antipruritic, antigerminative, antiplasmodial, antiesophageal cancer, and anticandidal The compounds are inexpensive and have been widely used in flavoring and fragrances since the beginning of the nineteenth century More recently, they have played a great role in the pharmaceutical industry because of their potential Monoterpenes are also included in the category of nutraceuticals, which represent an industry in excess of US$75.5 billion with prospects of growing to US$167 billion by 2010 [1] 1.2 Biosynthesis and Structural Diversity Modern methods of separation and structure determination, as well as the advent of radioisotope techniques, have led to a very rapid advance in knowledge of the route of biosynthesis of this class and the other types of terpenoids over the last 30 years Medicinal Plant Research in Africa DOI: http://dx.doi.org/10.1016/B978-0-12-405927-6.00001-1 © 2013 Elsevier Inc All rights reserved Medicinal Plant Research in Africa Several reviews, of differing completeness, have outlined the routes to terpenoids and steroids [2À8] in general and monoterpenes in particular [9,10] One important conclusion that emerges is the accuracy with which chemical theory can predict the course of the biochemical processes Enzymes exploit the innate reactivity of their substances, and the biosynthetic routes can be dissected into unit steps such as elimination, electrophilic addition, and WagnerÀMeerwein rearrangement that are controlled by the stereoelectronic factor known to operate in nonbiological systems Even the reactivity of apparently nonactivated atoms can usually be rationalized in terms of conformational and electronic changes imposed by postulated substrateÀenzyme or substrateÀcofactor linkages The well-established patterns found can be used to asses feasible structures for novel terpenoids and to design biogenetic-type synthesis 1.2.1 Biosynthetic Pathways 1.2.1.1 Isoprene Rule The earliest attempt to rationalize the pattern of structures of the monoterpenes was the rule proposed by Wallach in 1887, who envisaged such compounds as being constructed from an isoprene unit (1) (Figure 1.1) Thirty years later, Robinson extended this isoprene rule by pointing out that in monoterpenes, and such higher terpenes as were then known, the units were almost invariably linked in a headto-tail fashion, as shown for limone (2) and camphor (3) However, many higher terpenes and a few monoterpenes were later found not to obey this amended rule, and Ruzicka and his collaborators [11,12] proposed a biogenetic isoprene rule This generalization, which is now universally accepted, states that naturally occurring terpenoids are derived either directly or by way of predictable stereospecific cyclization, rearrangement, and dimerizations form acyclic C-10, C-15, C-20, and C-30 precursors geraniol, farnesol, geranylgeraniol, and squalene, respectively This rule implies a common pathway of biosynthesis for the whole family and any proposal for irregular biogenetic routes must be treated with reservations Although isoprene has been formed on pyrolytic decomposition of some monoterpenes, it is not found in plants, and much speculation has occurred around the nature of the active isoprene of the condensing unit, ranging from apiose to tiglic acid The C-5 unit was also postulated to arise from degradation of carbohydrates, proteins, amino acids, and many other classes of plant metabolites or by elaboration of acetic acid, ethyl acetoacetate, or acetone These early views have been well Figure 1.1 Chemical structure of isoprene unit (1), limone (2), and camphor (3) O Monoterpenes and Related Compounds from the Medicinal Plants of Africa summarized [13,14] Many C-10 compounds have been implicated as progenitors of monoterpenes including citral [15], geraniol [16], nerol [17], limonene [18], linalool [19], ocimene [20], and others [21À24] None of these speculations were backed by experimental evidence of any kind 1.2.1.2 Acyclic Compounds and Cyclohexane Derivatives 1.2.1.2.1 Hypotheses The proposals of Ruzicka and his coworkers [11] for the pattern of monoterpene biogenesis are outlined in Figure 1.2 Several of the intermediates are formally represented as carbonium ions, but structurally equivalent species such as alcohols, phosphate esters, terpene glycosides, or sulfonium salts, either free or bonded to proteins, may be the reactants in vivo The scheme is extremely attractive; the formation OPP OH OPP OH OH 10 Borane skeleton Pinane skeleton 11 Carane skeleton Thujane skeleton Figure 1.2 Formation of acyclic monoterpene: myrcene (4), ctronellol (5), cis-ocimene (6), α-terpineol (10), and terpinen-4-ol (11) Medicinal Plant Research in Africa of acyclics such as myrcene (4), citronellol (5), or cis-ocimene (6) from geranyl pyrophosphate (GPP) has many in vitro analogies, and monocyclization of the ion (7) formed from neryl pyrophosphate (NPP) to give α-terpineol (10), or terpinen-4-ol (11) is also chemically reasonable, although the biochemical details are open to conjecture For the latter process, either epoxides (which have been isolated from several essential oils) [25] or sulfonium compounds formed with a thiol group of an enzyme [26] may be involved as outlined in Eq (1.1) and (1.2) Both of these types of intermediates are known to be implicated in the formation of rings in higher terpenoids, and interesting model systems for the synthesis of monoterpenes in vitro using sulfonium ylides have been developed; the elucidation of the importance (if any) of such routes in the plant must await the advent of suitable cell-free systems H ð1:1Þ O OH H S Enz + HS ð1:2Þ Enz H H Bicyclic skeletons of the pinane and borane series are (according to Ruzicka’s scheme) derived by internal additions of positive centers to double bonds within monocyclic frameworks in a direction governed either by electronic factors (Markovnikov addition) or by steric factors Hydride shift within the ion (8) followed by cyclization of gives rise to the thujane skeleton, and that of the caranes arises from an internal electrophilic substitution at the allylic position of the former carbonium ion This latter reaction, as given, is biochemically improbable, and an internal displacement (Figure 1.3) in an intermediate such as 12 (X ester) or the intermediary of a nonclassical ion (13) has been suggested [27], but both proposals beg the question A study of the mechanism of decomposition of certain unsaturated epoxides suggests that Eq (1.3) X 12 13 Figure 1.3 Suggested internal displacement in an intermediate in monocyclic monoterpenes Monoterpenes and Related Compounds from the Medicinal Plants of Africa is feasible and the mechanism could be modified to form other bicyclic monoterpenes directly from acyclic precursors; cf Eq (1.4) The generation of the intermediate OH OH O ð1:3Þ NADPH EnzSH ð1:4Þ O SEnz SEnz carbenes, or their formal equivalents, may be possible at the enzyme surface where water and other potential scavengers may be locally excluded No evidence is available to assess these hypotheses 1.2.1.3 Cyclopentane Derivatives 1.2.1.3.1 General Iridoids (Figure 1.4) are a family of compounds based on carbon skeleton (14) that can be regarded as being formed by cyclization of 15 They were originally isolated from the defensive secretions of Iridomyrmex, a genus of ant [28,29], but are now known to be widely distributed in higher plants, usually, but not invariably, as the OH CHO O O CHO HO OR c o O MeO2C OH 16 15 14 CHO 10 HO OG OG O HO O CO2Me O CO2Me 11 O 17 18 Figure 1.4 Structure of some iridoids HO 19 G=-β-D-glucose Medicinal Plant Research in Africa β-D-glucosides Several hundred iridoids and related compounds have been isolated from leaf, seed, fruit, bark, and root tissue of dicotyledons This widespread distribution in plant tissues may be a consequence of the water solubility endowed by the sugar residue, and contrasts with the storage and retention in specialized oil glands of the largely water-insoluble monoterpenes of the types considered previously Few systematic studies of chemotaxonomy have been made [30], although a simple field test is available to detect iridoids A decade ago it was suggested [31,32] that tetrahydropyranmethycyclopentane monoterpenes of this then unusual type were possible biogenetic precursors of the indole alkaloids; similar proposals were made for the formation of oleuropeine (16) and elenolide (17) More recent work has amply confirmed these speculations, and there is little doubt that loganin, or a close-related compound, does fulfill these roles Most of the biosynthetic studies on the iridoids have been concerned with their function as intermediates en route to indole alkaloids, and it is only recently that these monoterpenes have begun to be studied in their own right Loganin is also an intermediate in the biosynthesis of other iridoids and of secoiridoids formed by rearrangement and functionalization of the skeleton (14) [33,34] Its aglucone is unstable and the sugar moiety may play a solubilizing, transport-facilitating, and, very importantly, protective role; in particular, it may protect the C1-linked hydroxyl group (for numbering of the ring see 18; alternative systems are sometimes used) from oxidation until the appropriate stage in the biosynthetic scheme, when the sugar residue is cleaved off The fused bicyclic system of loganin accounts for of the 10 carbon atoms derived from the acyclic monoterpene precursor One of the remaining carbon is absent in some compounds that cooccur with, and are undoubtedly related to, the iridoids, although there is no formal biosynthetic demonstration for these relationships saved in the case of aucubin (19) [35] Unedoside (20) (Figure 1.5) [36] is the only compound so far characterized that has lost both peripheral carbons; none have been reported which have lost the C10 methyl group but not the C11 carboxyl group, whereas in contrast several families of compounds have lost the latter group but retained the former, e.g., aucubin (19) and catalposide (21); R p-hydroxybenzol) [37,38] Secoiridoids such as gentiopicroside (22) [39] may be derived from loganin or a close-related compound by cleavage of the C7ÀC8 bond yielding initially, in the case of loganin itself [40], secologanin (23) [41] The isolation of compounds such as foliamenthin (24) [42], sweroside (25) [43], and ipecoside (26) [44], as well as biosynthetic studies, provide further evidence that these groups of compounds are biogenetically related Other relatives are the alkaloids β-skytanthine (27) [45] and actinidine (28) [46]; most of these compounds occur as their glucosides, but in addition to those described, genipin (29) and a few others appear to be presenting plant tissues as their aglycones A diglucoside and a thioester are among interesting iridoids that have recently been characterized All the biosynthetic studies on this group of compounds have depended on investigation of the fate in intact plant tissue of specifically labeled and carefully chosen precursors, and these have often been supplemented by the isolation of suspected intermediates from the tissue Only a few plant species have been investigated, especially young shoots of Vinca rosea or Catharanthus roseus Monoterpenes and Related Compounds from the Medicinal Plants of Africa OG O OG OH OG O O O O HO RO 20 21 O O 22 OG OG OH O O OHC CO2Me CO OG O 23 O O O O G=β-D-glucose 25 O 24 OH OH HO N N NAc HO CO2Me OG MeO2C O 27 28 29 26 Figure 1.5 Chemical structure of unedoside (20), captaposide (21), gentiopicroside (22), secologanin (23), foliamenthin (24), sweroside (25), ipecoside (26), β-skytanthine (27), actinidine (28), and genipin (29) Whereas the broad outlines of the biosynthetic pathways have undoubtedly been unveiled, some of the minor details may be species or even tissue specific For example, differences in labeling patterns between the same compound found in the leaves and flowers may occur Generally the influence of this, and of other physiological parameters, on biosynthetic routes has been ignored, but studies on the formation of verbenalin (30) (Figure 1.6), β-skytanthine (27), and nepetalactone (31) have demonstrated the critical importance of these factors may have on labeling patterns The same substrate may also be an effective precursor of a particular iridoid in one plant species but not in another; for example, whole and sliced rhizomes of Menyanthes trifoliata did not incorporate [2-14C]MVA into loganin, whereas in V rosea the additive was an efficient and specific precursor [47] Data based on several different experimental approaches or procedures are thus desirable for investigation of any one species Experiments using the 4R and 4S isomers of [2-14C, 4-3H1]MVA have confirmed that the stereospecificity of formation of the two double bonds of geraniol used in loganin formation is similar to that found in terpene synthesis in general, and that direct condensation of isopentenyl pyrophosphate (IPP) with dimethyl allyl pyrophosphate (DMAPP) to give nerol rather than geraniol directly also does not occur in this class of compounds Geraniol, GPP, or some other derivative such as the enzymebound intermediate previously discussed, appears to be an obligatory precursor The use of (1R)- and (1S)-[2-14C,1-3H1]GPP has demonstrated that conversion of the C1 carbon into an aldehydic or equivalent oxidation level is also stereospecific, and the hydrogens at rogens at C2 and C6 geraniol are retained during its transformation into Medicinal Plant Research in Africa O OG OH O O O O O CO2Me G= β-D-glucose OG O 31 30 CHO2Me 32 OH N O MeO 33 N HO OCOMe CO2Me 34 Figure 1.6 Chemical structure of verbenalin (30), nepetalactone (31), plumieride (32), iridodial (33), and loganin (34) loganin However, if saturation of the C2/C3 double bond of geraniol is a prerequisite for the formation of loganin, then both reduction and subsequent removal of the added proton occur in a stereospecific fashion [48,49] The occurrence of foliamenthin (24) and related compounds also suggests that oxidation of the isopropylidene group in geraniol is essential for its conversion into loganin However, evidence from the incorporation of doubly labeled mevalonic acid (MVA) into indole alkaloids suggests that incorporation of the intact propylidene unit of geraniol takes place Such findings are now reconciled by our knowledge that oxidation occurs at both C9 and C10 of geraniol (Figure 1.7) and that equilibration of these two carbons of geraniol occurs during the biosynthesis of loganin and related compounds from geraniol Thus early studies [50] on the biosynthesis of plumieride (32) [51] proved that during its formation from geraniol the C9 and C10 atoms of the latter became biosynthetically equivalent, for 25% of the label present was located at the starred atoms in 32 when [2-14C]MVA was used as a precursor A similar pattern in loganin (18) was obtained with the same precursor and with [3-14C]MVA, and analogous results have been reported for all the iridoids, secoiridoids, and indole alkaloids that have been studied To account for the pattern in plumieride, iridodial (or irodial) (33) was proposed as an intermediate, but this compound is not a precursor of loganin or vindoline (34) in V rosea [52] The equilibration of carbon atoms equivalent to C9 and C10 of geraniol may, however, not always be complete and can vary with the physiological condition of the plant used However, the point was made that asymmetric labeling of the part of the molecule derived from IPP, common for the monoterpenes described in the previous section, is not as widespread a phenomenon for these cyclopentane derivatives 10-Hydroxygeraniol (35) and 10-hydroxynerol (36) (using the accepted numbering) have recently been shown to be precursors of loganin and of the indole alkaloid, and a reasonable route for loganin biosynthesis can be summarized in Figure 1.7 Complete randomization of 14C label from C9 and C10 of 35 was observed Several related monoterpenes—linalool, Monoterpenes and Related Compounds from the Medicinal Plants of Africa HO CH3 HOH2C CO2H H H HD HA HC HB 9 CH2OH HB 10 CH2OH (Hc, HD) OH a OH OH OHC 35 a b OH CHO OH OH 37 b a HO H C OG HB O H(Hc, HD) H B Co2R 18 H H H 41 CHO 36 OG CHO O CHO H 38 CO2R b OH CHO Co2R G=β-D-glucose HA, HB, HC, and HD refer to the 4S, 4R, 2R, and 2S hydrogens, respectively of MVA Figure 1.7 Formation of cyclopentane derivatives citronellol, and citral—were not significantly incorporated These results suggest that a further step after 35 and 36 in the biosynthesis of iridoids involves attack on C9 of 35 or 36 (or of the corresponding aldehydes) to give a hypothetical species such as 37 (route a, Figure 1.7) It is not known whether C5 or C10 is oxidized first, or if indeed there is a specific order 10-Hydroxynerol was a more efficient precursor than its isomer, and this suggests that the immediate precursors of the iridoids and indole alkaloids [53] have the cis double bond at C2 and C3 that is expected on stereochemical grounds The rate of isomerization of this double bond may play an important role in diverting GPP from its alternative function as a precursor of higher terpenoids It is also possible that cyclization may proceed prior to further oxidation at C9 of 10-hydroxynerol (route b, Figure 1.7) The only other intermediates that have been demonstrated between geraniol and loganin or loganic acid are deoxyloganin and deoxyloganic acid, respectively ((38), R Me, H), and both have been shown to be specific precursors of loganin [54] Deoxyloganin occurs together with loganin in V rosea and Strychnos nux-vomica [55] Neither the aglucone of deoxyloganin nor the isomers with the double bonds at the C6/C7 or C7/C8 positions were incorporated into the final product The final stage of loganin [56] biosynthesis is therefore envisaged as hydroxylation of deoxyloganin at C7, which data on loganic acid biosynthesis suggest is stereospecific, like other biological hydroxylations Both 10 Medicinal Plant Research in Africa deoxyloganin and loganic acid occur in V rosea, and a cell-free system from this plant can convert the acid into loganin; thus a dual pathway is suggested in which methylation can occur at different points (Figure 1.8) Similar and more complicated metabolic grids have been observed in the biosynthesis of other terpenoids, especially carotenoids, and others will be mentioned shortly Recent work on loganic acid and gentiopicroside [57À59] biosynthesized from 14C and 3H doubly labeled isomers of MVA and geraniol has confirmed the formation of geraniol and hence of the cyclopentane derivatives from MVA The stoichiometry of both the decarboxylation of MVAPP to give IPP and of the addition of IPP to DMAPP to give GPP is similar to that reported previously for other terpenoids and steroids Deviations from the expected 14C/3H ratio of activities of C7 of loganic acid were found that were similar to those reported in steroid synthesis Such results have been accounted for by the relatively slow rate of removal of DMAPP by prenyl transferase as compared to the rate of establishing the equilibrium between IPP and DMAPP by IPP isomerase Conversion of DMAPP into IPP in the latter equilibration would result in a partial loss of asymmetry of the 3H/1H pair at C2 of IPP No preferential labeling of the two isoprene units of loganic acid was observed However, such patterns can occur at the monoterpene level; formation of menthiafolin, a hydroxylated isomer of 24, from [2-14C]geraniol gave a product in which the two C-10 moieties were labeled in the ratio of 3:1 This finding suggests that either the monoterpene or its constituent units may be synthesized in different pools, which may correspond to intra- and extrachloroplastic sites of synthesis (both of which sites contain terpene synthesizing enzymes) The pools may be connected at the monoterpene-glucoside level as these compounds are water soluble However, the stage at which glucose is coupled to a monoterpene remains unknown; present evidence suggests that it is not the final step in loganin or iridoid biosynthesis The earlier findings indicate that iridoids may pass through several intra- and extracellular compartments during biosynthesis, and the distribution of iridoids in all types of plant tissues may provide further evidence for such tortuous pathways The changes in labeling pattern at C3 and C11 of certain iridoids and related compounds dependent on the age of the plant material may also be related to the need for the biosynthetic scheme to occur at several distinct sites Indeed, the observed 14C/3H isotope ratios of activities of C7 of loganic acid biosynthesized from 4R and 4S isomers of [2-14C,-4-3H1]MVA that have been discussed earlier may be the result of incomplete randomization at the two positions, since the OG O O CO2Me G=β-D-glucose 41 Figure 1.8 Chemical structure of loganin derivative Medicinal Plants Market and Industry in Africa 24.8 887 Conclusions In Africa, there is an enormous demand for medicinal plants for both domestic and commercial uses, resulting in a huge trade on the local, national, regional, and international levels This trade represents an important opportunity to rural communities as a source of both affordable medicine and income But there is a real opacity of the medicinal plant trade at the level of the assessment of data concerning demand and supply As most of the plants are collected from wild sources, conservation of biodiversity and protection of threatened species is an important issue, and governments need to introduce regulations and rules to provide guidelines to control the collection, cultivation, production, certification, registration, and marketing of medicinal plants in order to promote the development of African medicines in the most appropriate manner and to protect public health and safety References [1] Cunningham AB An Africa-wide overview of medicinal plant harvesting, conservation and health care In: Global Initiative for Traditional Systems of Health and FAO, editors Medicinal plants for forest conservation and health care Non-wood forest products series no 11 Rome, Italy: FAO; 1997 [2] McGinley M, Hogan CM Biodiversity in Africa In: Cutler J, editor Encyclopedia of Earth Cleveland, Washington, D.C.: Environmental Information Coalition, National Council for Science and the Environment United Nations Environment Programme; 2012 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and Chemistry Edited by Victor Kuete Department of Biochemistry, Faculty of Science, Univeristy of Dschang, Dschang, Cameroon AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Elsevier 32 Jamestown Road, London NW1 7BY, UK 225 Wyman Street, Waltham, MA 02451, USA First edition 2013 Copyright © 2013 Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangement with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN: 978-0-12-405927-6 For information on all Elsevier publications visit our website at store.elsevier.com This book has been manufactured using Print On Demand technology Each copy is produced to order and is limited to black ink The online version of this book will show color figures where appropriate Preface Today there are many scientific publications demonstrating the importance of African medicinal plants The pharmacopoeias of most African countries are available and contain an impressive number of medicinal plants used for various therapeutic purposes Many African scholars have distinguished themselves in the fields of organic chemistry, pharmacology, pharmacognosy, and other areas related to the study of medicinal plants However, to date, there is no global standard book on the nature and specificity of chemicals isolated in African medicinal plants; nor is there a book bringing together and discussing the main bioactive metabolites of these plants To place African research globally, I have considered it necessary to offer students and researchers from Africa and around the world, who are beginning to turn to African medicinal flora, this book, which explores the essence of natural substances from African medicinal plants and their pharmacological potential In light of possible academic use, this book also scans the bulk of African medicinal plants having promising pharmacological activities, even if their phytochemistry has not been described This book covers all aspects of phytochemistry and pharmacology related to the secondary metabolites isolated from medicinal plants from Africa, including terpenoids, phenolic compounds, and alkaloids Emphasis has also been placed on the biosynthetic pathways of the plant metabolites discussed, taking into account the latest knowledge in the field Hence, in the group of terpenoids, there is discussion of mono- (Chapter 1), sesqui- (Chapter 2), di- (Chapter 3), and tri-terpenoids, and steroids (Chapter 4) The chemical compositions and pharmacological potential of essential oils from African medicinal plants are discussed in Chapter In the group of phenolics, we also discuss, in a similar way, the simple phenols, phenolic acids, and related esters from the medicinal plants from Africa (Chapter 6), phenylpropanoids and related compounds (Chapter 7), coumarins and related compounds (Chapter 8), flavonoids and related compounds (Chapter 9), quinones and benzophenones (Chapter 10), xanthones (Chapter 11), lignans (Chapter 12), and tannins (Chapter 13) Alkaloids isolated from African plants are reported in Chapter 14, while Chapter 15 brings out information on ceramides, fatty acids, and other related compounds from the medicinal plants from Africa An emphasis has also been placed on the metabolites isolated for the first time from African medicinal plants, and those bioactive metabolites that have until now been isolated only in African plants Chapters 16 through 20 are devoted to African medicinal plants having good pharmacological activity and identified hit compounds This book finally discuss the legislation on medicinal plants in Africa (Chapter 23) and the medicinal xx Preface plant market and industry in Africa (Chapter 24), two topics that have not required great attention from scientists to date All these topics are discussed globally and technically in the book, with a focus on illustration of the different chemical structures This document is the first of its kind on African medicinal plants The book also opens the door for future volumes, which will update the various aspects according to the evolution of research at the continental level in the future The highlight of this book is an exhaustive compilation of scientific data from up to 60 top scholars from more than 15 countries, including Botswana, Cameroon, Canada, China, Egypt, Germany, Ghana, Japan, Kenya, the Netherlands, Nigeria, Saudi Arabia, the United States, South Africa, and Tanzania Finally, I would like to thank Sarah Lay, the editorial project manager, Radhakrishnan Lakshmanan, the production manager and Unni Kannan, the technical assistant at Elsevier for their help and fruitful collaboration Victor Kuete About the Editor Dr Victor Kuete is a scholar/scientist at the University of Dschang, Dschang, Cameroon He has been a fellow of TWAS (2007), AUF (2008), DAAD (2009), the University of Mainz in Germany (2010), Alexander von Humboldt (2012À2014), and an International Foundation for Science Grantee (2008À2009, 2012À2013) His research program is focused on pharmacognosy, and he mainly investigates African medicinal plants and isolated compounds as potential antimicrobial, antiviral, and antiproliferative agents This program emphasizes on multidrug-resistant phenotypes as well as the mode of action of active ingredients Dr Kuete is the author of more than one hundred scientific publications in the field of medicinal chemistry List of Contributors Tchoukoua Abdou Department of Organic Chemistry, Faculty of Science, University of Yaounde´ 1, Cameroon Berhanu M Abegaz African Academic of Sciences, Nairobi, Kenya Christian Agyare Department of Pharmaceutics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Pantaleon Ambassa Department of Organic Chemistry, Faculty of Science, University of Yaounde´ 1, Cameroon Stephen O Amoo Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa Francis M Awah Natural Product Research Unit, Department of Biochemistry, Madonna University, Elele Campus River State, Nigeria Maurice D Awouafack Department of Paraclinical Sciences, University of Pretoria, Onderstepoort, South Africa, and Laboratory of Natural Products Chemistry, Department of Chemistry, University of Dschang, Dschang, Cameroon Veronique Penlap Beng Laboratory for Tuberculosis Research, Biotechnology Centre, University of Yaounde´ 1, Yaounde´, Cameroon Yaw Duah Boakye Department of Pharmaceutics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Krishna Prasad Devkota Molecular Targets Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD Jean P Dzoyem Department of Biochemistry, University of Dschang, Dschang, Cameroon Thomas Efferth Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany Jacobus N Eloff Department of Paraclinical Sciences, University of Pretoria, Onderstepoort, South Africa xxii List of Contributors Kenneth O Eyong Department of Organic Chemistry, University of Yaounde 1, Yaounde, Cameroon Aime´ G Fankam Department of Biochemistry, Faculty of Science, University of Dschang, Cameroon Ghislain W Fotso Department of Organic Chemistry, Faculty of Science, University of Yaounde´ 1, Cameroon Rebecca Hamm Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany Maurice Mmaduakolam Iwu International Centre for Ethnomedicine and Drug Development, Nsukka, Nigeria Justin Kamga Department of Organic Chemistry, Faculty of Science, University of Yaounde´ 1, Cameroon Mutiu Idowu Kazeem Department of Biochemistry, Lagos State University, Ojo, Nigeria Guy B Kougan Department of Organic Chemistry, University of Yaounde´ 1, Yaounde´, Cameroon Victor Kuete Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon Oladipupo A Lawal Department of Chemistry, Lagos State University, Lagos, Nigeria Mohamed S Marzouk Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, and Chemistry of Natural Products Group, Center of Excellence for Advanced Sciences, National Research Center, Dokki, Cairo, Egypt Ofentse Mazimba Department of Chemistry, University of Botswana, Gaborone, Botswana Paulo Peter Mhame The Traditional Medicine Section, Ministry of Health and Social Welfare, Dar es Salaam, Tanzania Mainen Julius Moshi Department of Biological and Pre-Clinical Studies, Institute of Traditional Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania List of Contributors xxiii Mack Moyo Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa Mikhail Olugbemiro Nafiu Department of Biochemistry, University of Ilorin, Ilorin, Nigeria Jerald J Nair Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa Frederic Nana Department of Organic Chemistry, University of Yaounde´ 1, Cameroon Bhekumthetho Ncube Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa Ashwell R Ndhlala Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa Roland N Ndip Department of Biochemistry and Microbiology, University of Fort Hare, Alice, South Africa, and Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon Bonaventure T Ngadjui Department of Organic Chemistry, Faculty of Science, University of Yaounde´ 1, Cameroon Bathelemy Ngameni Department of Pharmaceutical Sciences and Traditional Pharmacopoeia, Faculty of Medicine and Biomedical Sciences, University of Yaounde´ 1, Cameroon David Darko Obiri Department of Pharmacology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Isiaka A Ogunwande Department of Chemistry, Lagos State University, Lagos, Nigeria Christopher O Okunji International Centre for Ethnomedicine and Drug Development, Nsukka, Nigeria, and USP Headquarter, Rockville, MD Newman Osafo Department of Pharmacology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana xxiv List of Contributors Herve´ Martial Poumale Poumale Department of Organic Chemistry, Faculty of Science, University of Yaounde´ 1, Yaounde´, Cameroon, and Department of Bioresource Engineering, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata, Japan Musa Oyewole Salawu Department of Biochemistry, University of Ilorin, Ilorin, Nigeria Louis Pergaud Sandjo Department of Organic Chemistry, University of Yaounde´ 1, Yaounde´, Cameroon Abdelaaty A Shahat Medicinal, Aromatic and Poisonous Plants Research Centre, King Saud University, Riyadh, Saudi Arabia, and Department of Phytochemistry, Center of Excellence for Advanced Sciences, National Research Center, Dokki, Cairo, Egypt Yoshihito Shiono Department of Bioresource Engineering, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata, Japan Girija S Singh Department of Chemistry, University of Botswana, Gaborone, Botswana Turibio Tabopda Department of Organic Chemistry, University of Yaounde´ 1, Yaounde´, Cameroon Pierre Tane Laboratory of Natural Products Chemistry, Department of Chemistry, University of Dschang, Dschang, Cameroon Nicoline F Tanih Department of Biochemistry and Microbiology, University of Fort Hare, Alice, South Africa Michel Kenne Tchimene International Centre for Ethnomedicine and Drug Development, Nsukka, Nigeria Emmanuel Mouafo Tekwu Laboratory for Tuberculosis Research, Biotechnology Centre, University of Yaounde´ 1, Yaounde´, Cameroon Vincent P.K Titanji Biotechnology Unit, University of Buea, Buea, Cameroon Emmanuel Tshikalange Department of Plant Science, University of Pretoria, Pretoria, South Africa Apollinaire Tsopmo Food Science and Nutrition, Department of Chemistry, Carleton University, Ottawa, ON, Canada List of Contributors xxv Johannes Van Staden Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa Robert Verpoorte Institute of Biology, Leiden University, Leiden, The Netherlands Katrin Viertel Department of Pharmaceutical Biology, University of Mainz, Mainz, Germany Igor K Voukeng Department of Biochemistry, Faculty of Science, University of Dschang, Cameroon Jean Duplex Wansi Department of Chemistry, University of Douala, Douala, Cameroon Yanqing Zang College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, China Denis Zofou Biotechnology Unit, University of Buea, Buea, Cameroon ... Medicinal Plant Research in Africa deoxyloganin and loganic acid occur in V rosea, and a cell-free system from this plant can convert the acid into loganin; thus a dual pathway is suggested in. .. loganin, whereas 16 Medicinal Plant Research in Africa the indole alkaloids lose a C5 hydrogen Vincoside (42) seems to be the precursor of most indole alkaloids, being initially converted into... useful [1] Medicinal Plant Research in Africa DOI: http://dx.doi.org/10.1016/B978-0-12-405927-6.00002-3 © 2013 Elsevier Inc All rights reserved 34 2.1.2 Medicinal Plant Research in Africa Basic