Garcinia Plant Species of African Origin
Transcription
Garcinia Plant Species of African Origin
Understanding the medicinal potential of African Garcinia species Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Joseph Jangu Magadula & Zakaria Heriel Mbwambo Open Science Ethnobotanical, Pharmacological and Phytochemical Studies Joseph J. Magadula Zakaria H. Mbwambo First published 2014 by Open Science Publishers 228 Park Ave., S#45956, New York, NY 10003, U.S.A. ISBN: 978-1-941926-10-9 Copyright © 2014 Joseph J. Magadula Copyright © 2014 Zakaria H. Mbwambo All rights reserved. No part of this book may be reprinted or reproduced or utilized in any form or by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying and recording, or in any information storage or retrieval system, without permission in writing from the publishers. Cover design: Anne Harris, Syracuse Layout: Carrie Lee, Buffalo Printed in the United States of America. First Edition Trademark notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. A PDF version of this book is available for free in Open Science at www.openscienceonline.com. This work is licensed under the Creative Commons Attribution-NonCommercial 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/3.0/ This book is dedicated to the late Professor Zakaria H. Mbwambo who passed away on 19th July 2014 while it was at its publishing/printing stage Contents Foreword.......................................................................................................... 7 Preamble (About This Book) ........................................................................... 9 Acknowledgements ....................................................................................... 11 General Introduction ...................................................................................... 13 Chapter 1 1.1 Tanzanian Garcinia Species................................................... 17 Introduction .......................................................................................... 18 1.2 Tanzanian Floristic Regions ................................................................. 18 1.3 Distributions of Garcinia Plant Species in Tanzania ........................... 20 1.4 Basic Features of Selected Garcinia Plant Species .............................. 23 1.4.1 Garcinia acutifolia N. Robson .................................................. 24 1.4.2 Garcinia bifasculata N. Robson ................................................ 25 1.4.3 Garcinia buchananii Bak .......................................................... 26 1.4.4 Garcinia edulis Exell ................................................................. 27 1.4.5 Garcinia ferrea Pierre ............................................................... 28 1.4.6 Garcinia huillensis Welw. ex Oliv ............................................ 28 1.4.7 Garcinia indica DC ................................................................... 29 1.4.8 Garcinia kingaensis Engl .......................................................... 30 1.4.9 Garcinia livingstoneii T. Anders ............................................... 31 1.4.10 Garcinia mangostana L. .......................................................... 32 1.4.11 Garcinia pachyclada N. Robson ............................................. 33 1.4.12 Garcinia semseii Verdc ........................................................... 34 1.4.13 Garcinia smeathmannii (Planch. & Triana) Oliv. ................... 35 1.4.14 Garcinia volkensii Engl ........................................................... 35 1.4.15 Garcinia xanthochymus Hook. F. ............................................ 36 Chapter 2 Ethnobotany of African Garcinia Plants .............................. 39 2.1 Introduction .......................................................................................... 40 2.2. Ethnopharmacology of African Garcinia Plants ................................. 40 6 Contents Chapter 3 Pharmacological Activities of African Garcinia Plants ....... 45 3.1 Introduction .......................................................................................... 46 3.2 Antimicrobial Activity.......................................................................... 47 3.3 Antimalarial Activity ............................................................................ 60 3.4 Anticancer Activity .............................................................................. 61 3.5 Antioxidant Activity ............................................................................. 64 3.6 Antiviral Activity.................................................................................. 68 3.6 Other Biological Activities ................................................................... 70 Chapter 4 Phytochemistry of African Garcinia Plants ......................... 75 4.1 Introduction .......................................................................................... 76 4.2 Benzophenones ..................................................................................... 85 4.2 Flavonoids ............................................................................................ 86 4.3 Triterpenoids......................................................................................... 87 4.4 Xanthones ............................................................................................. 88 4.5 Other Compounds ................................................................................. 89 References .................................................................................................... 97 Appendix List of African Garcinia Species-Countrywise ................... 109 Foreword The search for plants that heal still represents a fascinating task. Before the Synthetic Era, almost all medicines were obtained from plant tissues and organs: roots, barks, stems, leaves, flowers and fruits. Self-medication was also observed in non-human primates to control parasitic infections and provide relief from gastrointestinal upsets. Therefore, in these terms, it seems that medicinal plant-animal coevolution is more ancient than the medicinal plant-human one, and that self-medicative behavior of non-human primates represented the evolutionary force for human traditional herbal medicine. The history of pharmacognosy is full of famous examples: the antimalarial alkaloid quinine from Cinchona tree, cardiac glycosides from Digitalis spp., curare from Chondrodendron tomentosum, the antipsychotic indole alkaloid reserpine from Rauwolfia serpentina and, among anticancer drugs, taxol from Taxus brevifolia, vincristine and vinblastine from Catharanthus roseus and camptothecin for Camptotheca acuminata. Garcinia species enrich this plentiful scenario, by virtue of their bio- and chemodiversity and healthy properties. In this book, the authors provide a comprehensive and updated survey on African Garcinia plants, with emphasis on eastern Africa species, focusing on botanical, ethnobotanical, ethnopharmacological and phytochemical aspects. The authors are very expert in the field of Garcinia research, as shown by their relevant publications on these topics. Professor, Marcello Iriti, 2014 Editor-in-Chief European Journal of Medicinal Plants Preamble (About This Book) This book has been written as a way of documenting the research results done by the authors and other researchers over years on the African Garcinia plants. Generally, the book is based on the area of academic training of the authors, which is the organic chemistry and in particular, the Chemistry of Natural Products. This book has been arranged in four chapters. The first chapter gives an overview of the Garcinia plant species growing in Tanzania, a country of domicile of the authors of this book. Furthermore, the localities in Tanzania where the plants are collected are included together with the basic features of some Garcinia plants growing in Tanzania. Chapter two is devoted to the ethnobotanical information on the genus Garcinia whereby general botanical description of a Garcinia plant is given. In addition, the traditional uses (ethnopharmacological information) of Garcinia plants growing in Africa are included in a tabular form. Chapter three is committed to the pharmacological activities of African Garcinia plants. This includes the biological activities on various crude extracts and compounds from African Garcinia plants, including antibacterial, antimalarial, cytotoxic, antioxidant, antifungal and antiviral activities. The table included in this chapter contains biological activities of extracts from 13 African Garcinia plant species tested either in vitro or in vivo for various microorganisms. Furthermore, the structures (1-40) of some biologically active compounds are presented. Chapter four deals with the phytochemistry of African Garcinia plants, from which over 100 natural product compounds have been isolated. The major 10 Preamble (About This Book) classes of compounds reported being benzophenones, flavonoids, triterpenoids and xanthones. In this chapter, it has been revealed that G. kola which is reported to grow in many West and Central African countries is the most studied plant among the African Garcinia species both pharmacologically and phytochemically points of view. It is our trust that, this book will provide potential and useful reference materials for the natural products researchers. It will also offer useful academic and technical information to ethnobotanists, ethnopharmacologists, pharmacologists, phytochemists and foresters in Africa and all over the global. We hope that you will enjoy reading this book. & Joseph Jangu Magadula [Dip Ed, BSc Ed (Hons), MSc (chem.), PhD] Zakaria Heriel Mbwambo [MSc Pharm, PhD] Dar es Salaam, 2014 Acknowledgements It is believed that a scientific worker can’t produce a document in the absence of professional and social interaction with other people. The academic and research knowledge and ability invested in the authors of this book are the result of contribution and nurturing of many people. So, it was thought to be wise and sensible idea to mention few of them, among the many. First of all we would like to thank God, for keeping us strong. He is constantly embracing us and took us through even during difficult moments. He is always our Rock and Savior. We wish to acknowledge the contribution made by our former mentors whose inspirations and guidance were the key for us to pursue the academic career in the field of organic chemistry and later specialize in Natural Products Chemistry. In this regard, we would like to mention and thank Professors Mayunga H. H. Nkunya, Dulcie A. Mulholland, Neil Crouch, A. Douglas Kinghorn and Dr Cosam J. Chiwanga who guided us during different stages of our academic and research careers. We wish also to acknowledge the contribution made by our research collaborators from different parts of the world. To mention the few, Professors Berhanu Abegaz (then in Botswana, now in Nairobi-Kenya), Supinya Tewtrakul (Thailand), K. H. Lee (USA), Pascal Richomme (France), Luc Pieters (Belgium), Pher Andersson (Sweden), Robinson Mdegela (Tanzania) and Drs Rebecca Goss (UK) and Matthias Heydenreich (Germany). A special thanks to our families for tolerating our absence when performing our research and academic duties and particularly during the time of producing this book. 12 Acknowledgements Finally, we would like to acknowledge the financial support from International Foundation for Sciences (IFS) for sponsoring the initial study of the genus Garcinia for plants available in Tanzania through grant # F/4572-1, the seed money from Swedish International Development Agency-Muhimbili University of Health and Allied Sciences (Sida-MUHAS) through the Directorate of Research and Publications. Commission for Science and Technology (COSTECH) for financial support on the ethnobotanical study, bioassays and herbal formulation of products from Tanzanian Garcinia plants through grant # RG47/09. General Introduction The genus Garcinia belongs to the family Clusiaceae, subfamily Clusioideae and the tribe Garcinieae. The name Garcinia honors a French botanist, Laurent Garcin (1683-1751) who lived and worked in India, where the genus is highly varied (Glen, 2004). This genus is considered to have over 450 plant species worldwide out of which about 300 species are found to the tropical Africa, Madagascar, tropical Asia, NE Australia, Polynesia, tropical America and China (Perry and Metzger, 1980). Here underneath is the taxonomic hierarchy of the genus Garcinia: KINGDOM Plantae DIVISION Magnoliophyta CLASS Eudicotyledoneae ORDER Malpighiales FAMILY Clusiaceae TRIBE Garcinieae GENUS SPECIES Garcinia (Ca 600 species worldwide) Currently, it is not well documented on the exact number of Garcinia species available in Africa, only scattered reports can be cited. For instances, in Madagascar and the Comoros alone there are about 32 Garcinia species reported to grow in the rain forests, with almost all of them being endemic to this country (Sweeney and Rogers, 2008) while in Tanzania only 15 Garcinia species are reported, most of them being scattered along the Eastern Arc Mountains (Magadula and Tewtrakul, 2010). In West Africa, about 50 Garcinia 14 General Introduction species are reported to grow, with 20 of them been reported from Cameroon (Agyili et al., 2007) and the rest distributed in other West African countries. In South Africa, only two (2) Garcinia species namely G. gerrardii and G. livingstoneii (African mangosteen) are reported to be indigenous and they are famous in traditional medicine (Palgrave et al., 2002). The distribution of Garcinia plant species in Africa indicated the plants to grow and being reported phytochemicaly and pharmacologicaly from only 20 African countries mainly in the south of Sahara region (Fig. 1). KEY: No any report Available report on Garcinia Species Fig. 1. Distribution map of African Garcinia plants showing countries reported to have Garcinia species. In total, about 80 Garcinia species are reported to grow in Africa. However, only 21 Garcinia species have been investigated phytochemicaly and/or pharmacologicaly. Currently, more than 130 compounds have been identified in Garcinia plants, of these 39% are xanthones, 27% are flavonoids, 10% are triterpenoids, 8% are benzophenones and 16% are other classes of compounds, with some of them being isolated from Garcinia plants for the first time. The General Introduction 15 phytochemical reports included in this book indicate that only a small fraction of African Garcinia plants have been studied for their chemical constituents. This necessitates further work to be done on an uninvestigated species. Due to the importance of Garcinia plants in terms of medicine, food and in plant species distribution and biodiversity, this report therefore intends to put together a record of what is known about the genus Garcinia in Africa. If not assembled and documented, such information, which is usually scattered in various literatures, herbaria records and other unpublished sources, will not be easily accessible to give comprehensive picture of the value of the African Garcinia species. It is anticipated that compilation of the information will also provide new direction in conservation and sustainable management of these important medicinal plants. Despite recent progress in phytochemical and pharmacological studies from the African Garcinia species, significant gaps still exist concerning both safety and toxicity aspects of some extracts and pure compounds. Further investigations have to be done including clinical studies, more phytochemical discoveries and subsequent screening tests aiming at opening new opportunities to develop drugs from Garcinia constituents. This book, therefore, provides useful clues to promote further investigations for the development of new phytopharmaceuticals or lead compounds from the genus Garcinia. Furthermore, this book will give basic information on sustainable exploitation and possible conservation strategies for African Garcinia plants. Tanzanian Garcinia Species 18 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies 1.1 Introduction Tanzania, like many other African countries, is endowed with tropical forests that are rich in natural resources, particularly plants. The country is divided into six major ecological zones, namely Lake Victoria Mosaic, Coastal Forest and Thickets, Afromontane Forest, Acacia-Savanna and Grasslands, Acacia Commiphora Thornbush and Miombo forests/woodlands, while the floristic regions are known to be eight, T1-T8. Every zone/region has its characteristic flora/plants and some uniqueness in terms of medicinal value of plants (Stuart et al., 1990). Our ethnobotanical survey and the literature report revealed that Garcinia plants grows at least in almost all ecological and floristic zones except T2, where there is no any Garcinia plant species being reported (Bampss et al., 1978). 1.2 Tanzanian Floristic Regions Tanzanian flora is within the Tropical East African Flora which comprises of about 21,650 vascular plant species. Tanzania alone has over 10,650 higher plant species, out of which about 2,500 species are indigenous whereas more than 1200 plant species are endemic. Currently, Tanzania has eight (8) floristic ecozones, T1-8 (Fig. 2), each zone being characterised by unique features of plant diversity, including the richest Eastern Arc Mountains as one of the biodiversity hot spots of Tanzania. It spreads and covers all parts of T3 and T6 floristic regions and is reported to contain about 2000 plant species with 25 – 30% being endemic to the forests and forest edges of the mountains (Burgess et al., 2002). Tanzanian Garcinia Species 19 Fig. 2. Tanzanian Floristic Regions. Each floristic zone covers a certain number of political regions in Tanzania as indicated in Table 1 below. Table 1. Floristic zones and their corresponding political regions in Tanzania. Zone Regions T1 Geita, Mwanza, Kagera, Mara, Simiyu and Shinyanga T2 Arusha, Manyara T3 Kilimanjaro, Tanga T4 Kigoma, Rukwa, Tabora T5 Dodoma, Singida T6 Coastal, Dar es Salaam, Morogoro T7 Iringa, Mbeya T8 Lindi, Mtwara, Ruvuma P Pemba Z Zanzibar 20 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies 1.3 Distributions of Garcinia Plant Species in Tanzania The distribution of the Garcinia plants in Tanzania indicated these plants to grow in almost all eight (8) floristic zones. A total of 15 Garcinia plant species are known from different habitats ranging from the altitude of 400 to 2300 m high. Different studies have been done to establish potential biodiversity of Tanzanian forest potentials. A study to determine richness of vascular endemic plants of the Uluguru Mountains, in Morogoro region (T6), identified about 108 plant species to be endemic to the Uluguru Mountains. From this study, only one Garcinia species, namely G. bifasculata, was reported to be endemic to the Kimboza Forest Reserve (Temu and Andrew, 2008). In another study on the East and West Usambara mountains (T3), about 150 vascular plant species were reported to be endemic (Polhill, 1968) from which two Garcinia species, namely G. volkensii and G. buchanannii, are indigenous and four Garcinia species namely G. edulis, G. ferrea, G. mangostana and G. xanthochymus, are exotic (Bamps et al., 1978). In Zanzibar, only three Garcinia species have been cultivated including G. mangostana (at Kibweni and Kizimbani areas), G. xanthochymus (at Zanzibar fide) and G. indica (at Migombani and Mtoni areas). The complete list of Tanzanian Garcinia species include G. acutifolia N. Robson, G. bifasculata N. Robson, G. buchananii Bak., G. edulis Exell, G. ferrea Pierre, G. huillensis Welw. ex Oliv., G. indica DC., G. kingaensis Engl., G. livingstonei T. Anderson, G. mangostana L., G. pachyclada N. Robison, G. smeathmannii (Planch&Triana) Oliv., G. semseii Verdc, G. volkensis Engl. and G. xanthochymus (Roxb. T. Anders), (Table 2). Tanzanian Garcinia Species 21 Table 2. Garcinia plant species found in Tanzania. Name Status Habit Indigenous Shrub, 2-3 Dry evergreen m forest, 100 m 1 G. acutifolia 2 G. Endemic bifasciculata 3 G. buchananii Indigenous Habitat Swamp forest Shrub, 4-6 (area of m limestone soil), 400 m Evergreen Tree/shrub, riverine forest, 2-15 m 60-1800 m Distribution Region Pugu Forest Reserve Litipo Forest Reserve T6, Coastal T8, Lindi Kimboza Forest Reserve T6, Morogoro Amani Nature Reserve T3, Tanga Karagwe Ukerewe 500-800 m 4 G. edulis Exotic 5 G. ferrea Exotic 6 G. huillensis Indigenous 7 G. indica Exotic 8 G. kingaensis Indigenous 9 G. livingstoneii Indigenous Shrub, 2-8 Deciduous m woodland, T1, Bukoba T1, Mwanza Mahali Mts, Kassangazi river-Mpanda T4, Rukwa Karagwe T1, Kagera Rondo plateau, Mchinjiri Kanga Forest Reserve Amani Nature Reserve Amani Nature Reserve T8, Lindi T6, Morogoro T3, Tanga T3, Tanga Lugoda village T7, Iringa Zanzibar (at Migombani and Mtoni) Zanzibar Tree, 3-15 Evergreen forest, Lugoda village m 1200-2300 m Fonera Forest Reserve Kanga Forest Reserve Madenge Forest hill Woodland, Shrub or thicket and Pugu Forest small tree, grassland, Reserve 3-18 m 0-1650 m T7, Iringa T7, Mbeya T6, Morogoro T7, Iringa T6, Coastal 22 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Name Status Habit Habitat Distribution Region Kazimuzumbi village Chalinze village 300-400 m 10 G. mangostana Exotic G. 11 pachyclada Indigenous 12 G. semseii Endemic 13 G. Indigenous smeathmannii Woodland and Shrub, 2-5 shrubby m grassland, 0-1500 m Tree, 3-15 Rain forest, m 210-1800 m Tree Riverine forest, 1000-1600 m Kimboza Forest Reserve Amani Nature Reserve Zanzibar (at Kibweni) T6, Morogoro T3, Tanga Zanzibar Ufipa district, Kasanga village, near Ngolotwa T4, Rukwa Kimboza Forest Reserve T6, Morogoro Kihansi T7, Iringa Manyangu T6, forest-Nguru MTS Morogoro T4, Mukugwa-Kibondo Kigoma Mwalesi-Rungwe T7, Mbeya Lupembe-Njombe T7, Iringa 14 G. volkensii 15 Indigenous G. Exotic xanthochymus Much-bran Evergreen forest, Amani Nature ched tree, 960-2400 m Reserve 2-20 m Ikwamba Forest 1520-1980 m reserve Kanga Forest 1300-2000 m Reserve Mamboto Forest 1600-1760 m Reserve Uluguru South Forest Shagayu forest, Lushoto T3, Tanga T6, Morogoro T6, Morogoro T6, Morogoro T6, Morogoro T3, Tanga Barankata area, Moshi T3, Kilimanjar o Amani Nature Reserve T3, Tanga Zanzibar Zanzibar Tanzanian Garcinia Species 23 1.4 Basic Features of Selected Garcinia Plant Species Plants from the genus Garcinia are usually evergreen trees or shrubs and dioecious and most of them grow in lowland rainforests or along riverines (Peres and Nagem, 1997). Most notably, they are trees or shrubs, secreting yellow latex when cut (Fig. 3) and generally glabrous. Leaves opposite or whorled, with latex canals; petiole bases usually strongly excavated. Inflorescences in axillary fascicles, rarely branched, or flowers solitary, axillary or terminal. Flowers bisexual and/or unisexual (plants usually dioecious or polygamous). Sepals 2-4(5), mostly imbricate; petals 2-4(-6), white, yellow, or red, decussate or imbricate, the pairs often of different sizes. Stamens free, variously fasciculate, or connate into a central mass, numerous in staminate flowers, fewer in bisexual flowers; anthers short. Ovary 2-12-locular, often absent from staminate flowers; ovule 1 per locule; styles short or lacking; stigmas expanded. Fruit a berry, mostly 1-locular, smooth to verrucose, leathery, ellipsoid to globose or ovoid, the mesocarp often juicy and sweet. Seeds 1-4; cotyledons minute. (http://www.mobot.org/MOBOT/research/ven-guayana/clusiaceae/page6.shtml) a b Fig. 3. (a) Stem bark of G. semseii showing yellow exudates and (b) G. semseii showing some leaves. 24 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Fruits have been observed to have one to four seeds with fleshy, smooth or verrucose glabrous or puberulous berry (Bamps et al, 1978). Fruits of many Garcinia species are edible, particularly those of an African mangosteen (Figure 4) and are highly eaten by wild animals as well as by humans. Fig. 4. Fruits of G. livingstoneii. A survey conducted to locate the Tanzanian Garcinia species indicated that some of them are threatened for extinction due to habitat destruction. A good example is G. acutifolia formerly reported to grow in Pugu Forest, Coastal region, which was currently wiped out from this area (Bamps et al., 1978). This survey, therefore, was able to locate and identify 15 Garcinia species growing in Tanzania as described in the following sub-sections. 1.4.1 Garcinia acutifolia N. Robson The botanical description of G. acutifolia indicate that the plant is a shrub or small tree, 2-3 m. high, glabrous; branches slender, narrowly 4-winged. Leaves are opposite, petiolate; lamina, chartaceous, bright green, concolorous, ovate to lanceolate or elliptic, shortly and usually very acutely acuminate at the apex. Tanzanian Garcinia Species 25 Male flowers with 2 antisepalous stamen-fascicles, each of 3 stamens, with filaments completely united and anthers sessile, oblong or elliptic, curved or straight, not septate. Fig. 5. Aerial parts of G. acutifolia at Litipo Forest Reserve, Lindi, Tanzania. This plant is mostly found among dry coastal forest species reported to grow in Mozambique and Tanzania and it is threatened by habitat loss. (Lovett and Clarke, 1998). In Mozambique, it grows between Muaguide and the Quissanga-Macomia crossroads, 2·3 km from Muaguide. In Tanzania, it is reported to grow in Pugu Forest Reserve, Coastal region at Kazimzumbwi area as well as at Litipo forest in Lindi region. 1.4.2 Garcinia bifasculata N. Robson This plant is reported to grow at Kimboza Forest Reserve; it is a tree found to grow at an altitude of 390 m along the swamp forest on limestone outcrops. The voucher specimen as well as the photo was taken at the site. Neither flowers nor fruits were observed during the time of visit to the Kimboza forest reserve. 26 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Fig. 6. Aerial parts of G. bifasculata at Kimboza Forest Reserve, Morogoro, Tanzania. 1.4.3 Garcinia buchananii Bak It is a small evergreen tree with leaves being oblong or elliptic. The leaves and bark exude yellow sticky latex when cut. Lateral veins are evidently fixed on both surfaces. Flowers are greenish-yellow and observed in solitary or in small clusters. The fruits are edible as they are fleshy, spherical and yellow when ripe. Fig. 7. Aerial parts and fruit of G. buchanannii. Tanzanian Garcinia Species 27 This plant is widely distributed, ranging from Sudan southwards through Eastern Africa to Angola, Mozambique and Zimbabwe. In Tanzania, this plant is reported from Amani Nature Reserve, Ukerewe, Kanga Forest Reserve (Morogoro), Gombe Forest Reserve (at Kakombe valley-Kigoma), Mwihana Forest Reserve (West Udzungwa-Iringa) and in Karagwe (Kagera region). 1.4.4 Garcinia edulis Exell This is a small tree, 5-6 m tall, with a straight and dark brown trunk, producing yellow latex when cut. Leaves are opposite, stiff, 7-12 cm long and 3-5 cm wide. Flowers are whitish and small, produced in axillary groups of 1-15 at branch nodes (Fig. 8). Fruits are round, about 3 cm in diameter, with a thin orange to reddish peel with an aromatic sweet sour taste. Seeds are in 1 or 2. It is commonly known as ‘the lemon drop mangosteen’. The plant is propagated by seeds that germinate easily with flowering and fruiting takes about 3 years. Fig. 8. Aerial parts and flowers of G. edulis at Amani Nature Reserve, Muheza, Tanzania. The plant is very attractive; sometimes it is used as an ornamental tree. The earlier classification of this plant placed it in the genus Rhedia and hence it was 28 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies called Rhedia edulis. In Tanzania, it is cultivated at Amani Nature Reserve near Sigi River, in Muheza district, Tanga region. 1.4.5 Garcinia ferrea Pierre The common name for G. ferrea is Pursat mangosteen with a synonym to Garcinia benthamii Pierre. This plant grows up to 5-6 m high and in Tanzania is known to grow at Amani nature reserve, Muheza district, Tanga region. Fig. 9. Aerial parts and fruits of G. ferrea at Amani Nature Reserve, Muheza, Tanzania. 1.4.6 Garcinia huillensis Welw. ex Oliv The reported common names for this plant are Granite garcinia (English), Granite mangosteen (English) and Mutunduru (Shona) (Drummond, 1981). It is a small evergreen tree growing up to 4-5 m high. The leaves are oblong or elliptic, thick and leathery, exuding yellow sticky latex when broken. The veins are lateral and conspicuously etched on both surfaces. Flowers are solitary or in small clusters, axillary, greenish-yellow and short-lived with the flowering time Tanzanian Garcinia Species 29 being September to November. Fruits are always fleshy, spherical, yellow when ripe and are edible. Fig. 10. Aerial parts of G. huillensis at Igomaa village, Mufindi, Tanzania. The habitat of this plant is on granite kopjes, rocky outcrops and in riverine fringes with an altitude of about 900-1800 m. Its distribution ranges from Sudan southwards through eastern Africa to Angola, Mozambique and Zimbabwe (Smith & Allen, 2004). In Tanzania, G. huillensis is reported to grow from Lugoda (Iringa), Geita (24 km South of Geita Gold Mines) and Gombe Forest Reserve along Kakombe valley in Kigoma region. 1.4.7 Garcinia indica DC This plant is commonly known as ‘kokum’ in most parts of India. It is a tree with a dense canopy of green leaves being indigenous to India. Leaves are elliptic, oblong or oblong-lanceolate about 6-8 cm long and 3-4 cm broad. The flowers are fleshy, dark pink, solitary or in spreading cluster and the flowering period is November to February. The fruit is brownish or brownish-gray, marbled with yellow, and is crowned by the 4-parted, stalkless stigma. There are from 6 to 8 seeds, and the pulp is juicy, white, and delicious in taste and odor. The fruiting season is between April and May. 30 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Fig. 11. Aerial parts and Fruits of G. indica. The habitat of G. indica is always forest lands, riversides and wastelands. The plant prefers evergreen forests, but sometimes they also thrive in areas with relatively low rainfall. In Tanzania, it is repoted to grow in Zanzibar at Migombani and Mtoni areas. 1.4.8 Garcinia kingaensis Engl This plant is always found in the understorey of evergreen forest and forested ravines at an altitude range of 1350-2100 m. It is a small to medium-sized tree with main branches, it appears horizontal while the lateral branches are grooved and angular. When cut it gives yellow sap. Leaves are opposite, narrowly elliptic to oblong and they are dull bluish to grey-green. Flowers are in clusters on short spur-branchlets along the stems. Fruits are spherical and yellow to orange and they are edible. The flowering time is between September and October. Tanzanian Garcinia Species 31 Fig. 12. G. kingaensis showing flowers, at Lugoda village, Mufindi, Tanzania. In Tanzania, it is reported to grow at Lugoda (Iringa), Songea (Luwiru-Kiteza Forest Reserve), Fonera Forest Reserve (Mbeya), Kanga Forest Reserve (Morogoro-Turiani), Madenge Forest (Iringa) and Mwanihana Forest Reserve (West Udzungwa mountains-Iringa. The wood is hard and used for firewood, poles, tool handles, spoons, stools and milk pots while the sap gives yellow dye. As known for other Garcinia plants, fruits are edible. 1.4.9 Garcinia livingstoneii T. Anders It is an evergreen, small tree of up to 20 m high usually with dense rounded crown. Leaves are always in whorls of three, while flowers are in crowned fascicles of 5-15 and they attract insects due to their sweet nectar. Fruits are yellow or orange in colour while their shapes are always ovoid and they are edible. 32 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Fig. 13. Branchlets and Fruits of African Mangosteen at Kazimzumbwi, Kisarawe, Tanzania. It grows in a wide range of tropical Africa from from Côte d'Ivoire east to Somalia, and south to South Africa being commonly known as African mangosteen to its esteemed fruits. The distribution of the plant in Tanzania is high as it is reported to grow in Chalinze area, Pugu Forest Reserve and kisarawe at Kazimzumbwi village and it is called Mutumbi or Mpekechu (in Swahili). 1.4.10 Garcinia mangostana L. It is a small tree of 7-8 m high with dense heavy branched crown. The leaves are leathery. The petioles are short and thick. The flowers are 5 centimeters in diameter, 4-parted, bisexual, and borne singly or in pairs at the ends of the branchlets. The seeds are large, flattened- and embedded in snowy-white or pinkish delicious pulp. The mangosteen fruit is the size of a small apple, purple colored, with a hard rind. Inside there are typically five to seven seeds surrounded by a sweet, juicy cover (or aril). Dried fruits are well known for their medicinal uses. Tanzanian Garcinia Species 33 Fig. 14. Aerial parts and fruits of G. mangostana at Amani Nature Reserve, Tanzania. Although this plant is known to be native to South East Asia, it is cultivated in almost all tropical countries. It is a true mangosteen due to its valuable fruits. In Tanzania, G. mangostana is cultivated at Amani Nature Reserve, Muheza district, Tanga region. 1.4.11 Garcinia pachyclada N. Robson This appears as a shrub or small tree of about 5 metres high having thick branches with a grayish or corky bark. The bark secrets yellow and sticky latex when cut. Leaves are observed to be in whorls of three. Flowers are observed to be unisexual and clustered in axils or above the leaf-scars on mostly leafleded branches. G. pachyclada differs from G. livingstonei by its Uapaca-like habit (ascending branches), its thicker rough branches; its leaves are thickened, undulate margins, and its large flowers on short pedicels. It is a plant of plateau 34 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies woodland rather than riverine forest. In Tanzania, this plant is reported to grow in Sumbawanga (Rukwa) at Kasanga area-Ngolotwa. 1.4.12 Garcinia semseii Verdc This is a tree that grows to the height of about 15 mters, having slightly wrinkled branchlets and rough nodes. The leaves are opposite and they become reddish brown when dry. The plant always contains two flowers at the leafless nodes. Fruits are roughly warted and highly eated by monkeys. Fig. 15. Leaves and Fruits of G. semseii taken at Kimboza Forest Reserve, Morogoro district. This plant is endemic to Tanzania and its range description indicates to be known only from four localities including Kimboza forest reserve, Chita and Kihansi within the Udzungwa mountains and at Nguru mountain in Morogoro region. Tanzanian Garcinia Species 35 1.4.13 Garcinia smeathmannii (Planch. & Triana) Oliv. It is a small tree that grows to about 20 m high and haaving a bole of over 1 m in girth. It has a dark orangeish scaly bark exuding some yellow latex when cut. Leaves are simple and opposite while petioles are short or normal and entire margin. Flowers are dioecious and in fascicles of 5–30 in the axils of leaves. Fruits are purplish-green turning to yellow with 1-2·5 cm in diameter. Fig. 16. Leaves and Flowers of G. smeathmannii. The plant always grows in riverines and uplands to about 1500 m elevation. The distribution ranges from Angola, Congo, Gabon, Cameroon, Central African Republic and DR Congo. In Tanzania, it is reported from 48 km South of Kibondo at Mukugwe River, Rungwe at Mwalesi River, Njombe (upper Ruhudje river and Lupembe area-north of the river). 1.4.14 Garcinia volkensii Engl This is a highly branched plant growing to about 20 m high. Its bark is grey or brown and gives white/yellow exudates when cut. Leaves are simple, opposite or whorled while petioles are angled and/or narrowly winged. Flowers 36 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies are dioecious cream/green-white/pink and infloresence in axillary cymes. Fruits are green and turning yellow/orange/brown when ripe. Fig. 17. Aerial parts of G. volkensii at Shagayu Forest Reserve, Lushoto, Tanzania. The ecology of this plant is in understorey of evergreen rainforest as well as dry evergreen forest to an elevation of up to 2400 m. Its distribuition in Tanzania is from Ikwamba Forest Reserve, Kanga Forest Reserve, Mamboto Forest Reserve (all from Morogoro region), Amani Nature Reserve, Shagayu Forest Reserve (from Tanga region), Useri at Barankata area (Kilimanjaro region) and Mwanihana Forest Reserve (West Udzungwa-Iringa). 1.4.15 Garcinia xanthochymus Hook. F. It is a small evergreen tree growing up to about 15 m high with horizontal branches and a dense pyramidal crown. Leaves are narrowly oblong while fruits are pale orange to dark yellow with a diameter of about 9 cm. The fruit is edible Tanzanian Garcinia Species 37 and has a pleasant acid taste. It usally contains two seeds, sometimes is called yellow mangosteen or camboge. Flowering occurs between March and May. Fig. 18. Aerial parts and fruits of G. xanthochymus at Amani Nature Reserve, Tanzania. The tree is well adapted to shade and humid conditions. In Tanzania, the plant was cultivated at Amani Nature Reserve, near Sigi river, Muheza district, Tanga region. Ethnobotany of African Garcinia Plants 40 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies 2.1 Introduction Medicinal plants play an important role in the healthcare systems all over the world. Around 80% of general population in the world uses plants to treat several illnesses (UICN, OMS, WWF, 1993). Ethnobotanical studies are very important to reveal the past and present culture about plants. Human societies throughout the world have accumulated a vast body of indigenous knowledge over centuries on medicinal uses of plants, and for other related uses including poison for fish and hunting, purifying water, and for controlling pests and diseases of crops and livestock. In this respect, people are able to use and conceptualize plants in their local environments. For instance, medicinemen or herbalists have a good knowledge on botanical description including correct identification of plants for intended purposes. Hence, ethnobotany details the knowledge of plants by the local people and their usefulness as understood by the people of a particular ethnic group (Tor-Anyiin et al., 2003), particularly this study involves the scientific study of the traditional knowledge and customs of a people concerning plants and their medical, religious, and other uses. 2.2. Ethnopharmacology of African Garcinia Plants Many African Garcinia species have been reported to be used in traditional medicine for many centuries. Some of them have been studied and reported to have many ethnomedical uses. Among the effects reported are the treatment of head and abdomen pains, fever, ulcers, impotence, throat and bronchial infections, venereal diseases, diarrhea, hepatitis, asthma rheumatism, arthritis, Chapter 2 Ethnobotany of African Garcinia Plants 41 cancer, liver cirrhosis and cough (Table 3). Many literatures indicated Garcinia kola, a plant reported to grow in many Western African countries, to be the most studied Garcinia species in all aspects, including ethnomedical use, pharmacology and its phytochemistry. Sometimes, it is referred to as a “wonder plant” because every part of it has been found to be of medicinal importance (Dalziel, 1937). Ethnomedically, many Garcinia plants are used as a decoction, an infusion or as a juice. Most extracts are prepared with cold or hot water and are applied for the treatment of toothache, inflammations, for wound-healing, jaundice, ulcers, dysentery, as aphrodisiac, for fever, sleeping sickness, venereal diseases, liver cirrhosis, arthritis and respiratory track diseases. Other Garcinia plants are used as chewing sticks, fertilization stimulant, aid childbirth while some fresh or dried fruits are used as food. For instance, G. livingstoneii is commonly known as an ‘African mangosteen’ as it produces very tasty and delicious fruits while the powdered root is used as an aphrodisiac (Anorld & Gulumian, 1984). Hence, many Garcinia plants are known for different traditional uses (Table 3) while others are not reported for any ethnomedical use. 42 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Table 3. Traditional uses of some Garcinia plant species growing in Africa. S/N Scientific name Where collected Part used Traditional uses 1 G. afzelii Ghana Stem wood Guinea Root bark Cure aphrodisiac G. buchananii 2 G. epunctata 3 G. huillensis Vasileva (1969) Diarrhoea, dysentery, Stem bark abdominal Balemba et al. (2010) discomfort, pains impotence, chewing Adu-Tutu et al. Ghana Stem wood stick (1979) Watt and South Africa Stem bark Aphrodisiac Breyer-Brandwijk (1962) Tanzania DR Congo G. kola Adu-Tutu et al. (1979) Tanzania Tanzania 5 Impotence, chewing stick Reference Nigeria Root bark Used for insanity Mathias (1982) Stem bark Treat sleeping +Root bark sickness Cure venereal diseases, sores, Stem bark bronchitis, measles, dermatitis and as aphrodisiac Used for fever, inflammation, cough, Stem bark anthelmintic and respiratory track diseases Freiburghaus, et al. (1996) Bakana et al. (1987) Gill and Akinwumi (1986) Dried Fruit Treat arthritis Iwu & Anyanwu (1982) Fresh fruit Used as food Ebana et al. (1991) Used as an antiseptic Dried for cuts and sore fruitpeel throats Used as a chewing Dried root stick, Treat liver cirrhosis, inflammation of the respiratory tract, coughs Used for cough, tooth decay, gonorrhea (roots soaked in local gin) Used as fertilization Seed stimulant Iwu et al. (1990) Fadulu (1975) Iwu et al. (1990) Ebana (1991) Elujoba (1995) Chapter 2 Ethnobotany of African Garcinia Plants S/N Scientific name Where collected Part used Traditional uses Used as a masticatory, antidote Dried seed and inflammatory disorders Treat cough, abdominal colic, aphrodisiac and catarrh Treat diarrhoea, hepatitis, dysmenorrheal, gastroenteritis and asthma Treat bronchitis, diarrhoea, and throat infections 6 G. livingstoneii Tanzania Fruit Venda (RSA) Leaf G. lucida Kenya Root Somalia Root Used as food Used for toothache, impotency and aphrodisiac Used to aid Childbirth Treat abdomen pains Used as an aphrodisiac To treat gastric infections, antidote Stem against poison, aphrodisiac properties Treat stomach ulcers Leaf and liver diseases Used for dressing Sap (latex) wounds 43 Reference Iwu et al. (1990) Akintonwa and Essien (1990) Braide (1989) Adesina et al. (1995); Orie and Ekon (1993), Iwu 1993. Johns et al. (1984) Anorld and Gulumian (1984) Yu et al. (1982) Samuelsson et al. (1992) South Africa Root Palgrave et al. (2002) Taanzania Fotie at al. (2007) 7 G. mangostana. Madagascar 8 G. polyantha Cameroon 9 G. punctata Gabon Stem bark Treat headache 10 G. smeathmannii Cameroon Stem bark Novy (1997) Bouquet (1969) Akendengue and Louis (1994) Antidote, chew-stick Bouquet, 1969 and laxative Ophtalmia (eye Sap (latex) Bouquet, 1969 treatments) Bark latex Skin, mucosae Bouquet, 1969 Pharmacological Activities of African Garcinia Plants 46 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies 3.1 Introduction Plants remain rich and potential source of therapeutic compounds for the development of new drugs. Secondary metabolites obtained from plants have been a great source of many drugs for managing various diseases. Even if recent advances in biochemical engineering and other biotechnologies represent alternative sources of drugs, more than 70 % of the current therapeutic drugs derive their structures from plants used in traditional medicine (Chantarasriwong, 2010). Although many and new drugs including antibiotics have been developed in the last three decades, resistance to them by infectious microorganisms has increased. As a result, the search for new bioactive compounds from plants for pharmaceutical purposes has gradually increased worldwide (Kaikabo et al., 2009). Many recent biological studies on medicinal plants used as folklore remedies in the treatment of different ailments have attracted the attention of a number of researchers as possible alternatives to the existing incurable diseases and the problem of drug resistances. Globally, the problems of multiple resistance as well as emergence of new and resurrection of previously eradicated diseases have necessitated the continued effort to search for novel and effective drugs from medicinal plants to complement the existing synthetic drugs. Recent studies have indicated that Garcinia species possess a wide range of biological activities and led to a greater understanding of the pharmacology of various species, particularly in relation to the antimicrobial, anticancer, antiviral, antioxidant, antimalarial and other biological activities. These pharmacological studies supports to the traditional uses of Garcinia plants in treating different ailments by many African societies. Hence, reported pharmacological activities on crude extracts and compounds from African Garcinia plants indicated Chapter 3 Pharmacological Activities of African Garcinia Plants 47 various biological activities, including antibacterial (Ebana et al., 1991), antimalarial (Tona et al., 1999), cytotoxic (Sordat-Diserens et al., 1992), antioxidant (Farombi et al., 2002), antifungal (Kpakote et al., 1998) and antiviral activities (Bakana et al., 1987; Gustafson et al., 1992; Magadula, 2010) and other biological effects (Table 4). 3.2 Antimicrobial Activity The treatment of infectious diseases has existed for many years and, as a result, many reports of antimicrobial extracts and compounds from Garcinia species have been documented from various parts of Africa. Over 20 different crude extracts from more than 10 Garcinia plant species found in African flora have been investigated for antimicrobial properties (Table 4). One of the reports is on the ethanol extract of the dried stem bark of G. afzelii collected in Togo. This extract showed significant antibacterial and antifungal activities against Staphylococcus aureus and Asperigillus fumigatus (Kpakote et al., 1998). In another study from a Congolese plant, G. huillensis, the in vitro testing of the water extract of the stem bark indicated marked activity against Cytospora species (Laine et al., 1985), while the antibacterial activity was noted in the petroleum ether extract of this plant against Staphylococcus aureus with the minimum inhibition (MIC) of 62.5 μg/ml (Bakana et al., 1987). Garcinia kola, collected in Nigeria and Ghana is the most investigated species with all parts studied pharmacologically. Thus, in the study of the ethyl acetate extract of the dried seeds, good antibacterial and antifungal activities were observed against Bacillus subtilis and Aspergillus niger both at a concentration of 100 μg/ml (Madubunyi, 1995). Another study on the methanolic extract of G. kola indicated significant in vitro antimicrobial activities against some bacterial isolates comprising both Gram-positive and 48 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Gram-negative organisms tested at a concentration of 20 μg/ml. The zones of inhibition exhibited by the extract against the tested organisms ranged between 10 and 23 mm, while the zones of inhibition exhibited by streptomycin and tetracycline used as standard antibiotics ranged between 15 and 25 mm and, 12 and 25 mm, respectively (Adegboye et al., 2008). Significant antibacterial activities were reported from the water and ethanol extracts of the root bark of G. kola in a study conducted by Ebana et al. (1991). Furthermore, the study by Iwu (1993) indicated the plant to have significant antimicrobial and antiiflammatory activities. In the study by Akerele and co-workers on the the crude ethanol extract, aqueous and chloroform fractions of the seeds of Garcinia kola showed significant inhibitory activity against a range of clinical isolates of both Gram positive and Gram negative bacteria. The MIC values obtained ranged between 2.5 and 7.5 mg/ml for bacteria and fungi isolates, respectively (Akerele et al., 2008). Kpakote and co-workers investigated the dried stem barks of G. ovalifolia and G. polyantha for antibacterial activities. Significant result was obtained against Pseudomonas aeruginosa at a concentration of 4.0 mg /ml (Kpakote et al., 1998, Table 4). The acetone extract of G. livingstonei leaves was studied for antibacterial activity using bioautography and by determining the minimum antibacterial concentration against four nosocomial pathogens. Bioautograms showed that two compounds were mainly responsible for the antibacterial activity namely, amentoflavone (1) and 4''-methoxyamentoflavone (2) (Kaikabo et al., 2009). The antibacterial activity of the isolated compounds was determined against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa with both compounds exhibiting the MIC values ranging from 8-100 μg/ml (Kaikabo et al., 2009). Further studies on the Chapter 3 Pharmacological Activities of African Garcinia Plants 49 activities of compounds 1 and 2 were done against fast-growing non-pathogenic Mycobacterium smegmatis. In this study, compound 1 was reported to be the most active one with an MIC of 0.60 mg/ml, while the MIC of compound 2 and the positive control isoniazid against M. smegmatis were similar at 1.40 and 1.30 mg/ml, respectively. This indicates that some infections caused by M. smegmatis may be managed by these compounds (Kaikabo and Eloff, 2011). On the other hand, Garcinia plants used ethnomedically as chewing sticks have been investigated for their antimicrobial potential. Thus, from the antibacterial fraction of the root bark of G. kola, biflavanone GB-1 (3) was isolated as the major constituent. This compound showed significant antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) with MIC of 32 and 128 μg/ml respectively (Han et al., 2005). Xanthones is an important class of compounds from Garcinia plants due to its diverse biological activities. From the South African Garcinia plant, G. gerradii, three prenylated xanthones, garcigerrin A (4), B (5) and l2b-hydroxy-des-D-garcigerrin A (6) were tested for their activity against the plant pathogenic fungus Cladosporium cucumerinum using a TLC biossay. Garcigerrins were inactive at 50 μg/ml while compound 6 prevented growth of the fungus at a concentration of 0.2 μg/ml (Sordat-Diserens et al., 1989). From an African mangosteen, compounds 7-9 were tested for their activity against the plant pathogenic fungus Cladosporium cucumerinum, using a TLC bioassay with compounds 7 and 8 preventing the growth of the fungus at concentrations of 0.5 and 0.2 μg/ml respectively (Sordat-Diserens et al., 1992). In another study, smeathxanthone A (10) and smeathxanthone B (11) were isolated from a Cameroonian plant, G. smeathmannii and tested for their in vitro antibacterial 50 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies and antiyeast activities. These compounds showed a mild activity against a range of bacteria and yeasts (Komguem et al., 2005). Momo and co-workers investigated the methanol crude extract from G. lucida for its antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus, and Candida albicans. The result of the crude extract indicated a good inhibitory activity with a MIC value of 64 μg/ml on Candida albicans and it was inactive for other tested organisms (Momo et al., 2011). The isolated compounds from the CH2Cl2 fraction of G. lucida were not active except cycloartenol (12) which exhibited moderate and selective antimicrobial activity with IC50 of 512 μg/ml against E. coli and P. aeruginosa (Momo et al., 2011). Chapter 3 Pharmacological Activities of African Garcinia Plants OH OH HO 51 HO O O OH OH OH OR O HO O HO O R O 1 H OH OH OH OH O O OH 2 CH3 O OH OH O OH OH OH O OH OH O 6 OH O O O OH OH O 8 OH 9 OH OH O OH O O O 7 OH OH OH O O OH O 5 4 OH 3 O OH O O OH OH OH O O OH 10 11 12 Fig. 20. Structures of bioactive compounds isolated from some African Garcinia plants. 52 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Table 4. Biological activities of extracts from African Garcinia species. Plant species (Country) G. afzelii (from Togo) Part used Effects (Extracting In vivo (Organism tested) solvent) Antibacterial Dried Stem (Pseudomonas (EtOH) aeruginosa) Antibacterial Dried Stem (Staphylococcus (EtOH) aureus) Antifungal Dried Stem (Asperigillus (EtOH) fumigatus) Antiyeast (Candida Dried Stem albicans) (EtOH) G. edulis (from Tanzania) Antiviral (HIV-1 protease) Stem bark (Ethanol) Cytotoxicty (Artemia salina) Root bark (Ethanol) G. gerradii Larvicidal (Aedes (from South aegypti) Africa) Dried Leaf (CH2Cl2) Anticrustacean (Artemia salina) Dried Leaf (CH2Cl2) Molluscicidal (Biomphalaria glabrata) Dried Leaf (CH2Cl2) Antifungal (Cladosporium cucumerinum) Dried Leaf (CH2Cl2) Cytotoxicty (CA-COLON-SW 480) Dried Leaf (CH2Cl2) Cytotoxicty Dried Leaf (CA-HUMAN-COL (CH2Cl2) ON-CO-115) G. huillensis (from DR Antifungal (Cladosporium cucumerinum) Root bark Antifungal (Cytospora sp) Dried stem bark (H2O) In vitro Inactive- at a conc of 4.0 mg /ml Active- at a conc of 4.0 mg /ml Active- at a conc of 4.0 mg /ml Inactive- at a conc of 4.0 mg /ml Active with IC50 value of 9.2 µg/ml Active with LC50 value of 2.36 µg/ml Active- at a conc of 500.0 mg /ml Active- with LC50 value of 53.0 µg /ml Inactive- at a concentration of 400 ppm Inactive- at a concentration of 100 µg/plate Active- with IC50 value of <5.0 µg /ml Weak activitywith IC50 value of 7.0 µg /ml Active- at a concentration of 100 µg/plate In an agar plate, active at a conc of 1-10 Reference Kpakote et al. (1998) Kpakote et al. (1998) Kpakote et al. (1998) Kpakote et al. (1998) Magadula (2010) Magadula (2010) Cepleanu et al. (1994) Cepleanu et al. (1994) Cepleanu et al. (1994) Cepleanu et al. (1994) Cepleanu et al. (1994) Chapuis et al. (1988) Sordat-Dise rens, et al. (1989) Laine et al. (1985) Chapter 3 Pharmacological Activities of African Garcinia Plants Plant Part used Effects (Extracting In vivo species (Organism tested) (Country) solvent) Congo) Antiviral (Virus-Herpes Simplex 1) Dried stem bark (PetEther) Dried stem Antiviral bark (Virus-Coxsackie) (PetEther) Dried stem Antiviral bark (Virus-Poliovirus 1) (PetEther) G. huillensis (from Tanzania) G. kingaensis (from Tanzania) G. kola (from DR Congo) G. kola (from Nigeria) In vitro 53 Reference mg /ml Inactive-the conc was not given Inactive-the conc was not given Inactive-the conc was not given In an agar plate, seen active with MIC value of 62.5 µg /ml Bakana et al. (1987) Bakana et al. (1987) Bakana et al. (1987) Antibacterial (Staphylococcus aureus) Dried stem bark (PetEther) Antitrypanosomal (Trypanosoma brucei) Dried stem + root (CH2Cl2) Active- with IC50 value of 4.4 µg /ml Freiburghau s et al. (1996) Antiviral (HIV-1 protease) Root bark (Ethanol) Active with IC50 value of 15.2 µg/ml Magadula (2010) CNS stimulant Dried stem bark (H2O) Not active in rat and the dose was not stated CNS depressant Dried stem bark (H2O) Not active in rat, the dose was not stated Antioxidant Dried fruit (H2O) Bronchodilator Fresh fruit (Human adult, male) (H2O) Active in rat liver at a conc of 2.5 mg/ml 19 healthy volunteers aged 17-25 years were used for this study. Decoction was taken orally at a dose of 15.0 gm/person. Weak activity was observed in 1 hour after treatment with results been Bakana et al. (1987) Sandberg and Cronlund (1977) Sandberg and Cronlund (1977) Adegoke et al. (1998) Orie and Ekon (1993) 54 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Plant Part used Effects (Extracting In vivo species In vitro (Organism tested) (Country) solvent) significant at p < 0.05 level Active at a dose of 10 ml/kg. The rats were given partial hepatectomy and Hepatoprotective Saline Ext enzyme (glucose-6-phosph atase) activity was inhibited by 31%. Protein & DNA synthesis Commercial inhibition at a Hepatoprotective sample of dose of 5 ml/kg kernel (H2O) Rats were given partial hepatectomy Strong activity Molluscicidal at a conc of (Biomphalaria Dried leaf 100 ppm pfeifferi, Lymnaea (MeOH) leading to natalensis & 100% Bulinus globosus) mortality Antibacterial Active but the Dried root (Streptococcus-beta concentration bark (EtOH) hemolytic) was not given Active but the Antibacterial Dried root concentration (Proteus mirabilis) bark (H2O) was not given Antibacterial Active but the Alkaloid (Klebsiella concentration fraction pneumoniae) was not given Antibacterial Active but the Glycoside (Pseudomonas concentration mixture aeruginosa) was not given Active but the Antibacterial Dried root concentration (Escherichia coli) bark (H2O) was not given Active in rat at a dose of 500 mg/kg Dried seed with inhibition of Hypotriglyceridemia (flavonoid enzyme increase fraction) versus CCl4-Induced hepatotoxicity Dried seed Active in rat at a Antihepatotoxic (flavonoid dose of 500 mg/kg Reference Adegoke et al. (1998) Oruambo (1989) Okunji and Iwu (1988) Ebana et al. (1991) Ebana et al. (1991) Ebana et al. (1991) Ebana et al. (1991) Ebana et al. (1991) Braide (1991a) Braide (1991a) Chapter 3 Pharmacological Activities of African Garcinia Plants Plant Part used Effects (Extracting In vivo species (Organism tested) (Country) solvent) fraction) with inhibition of enzyme increase versus CCl4-Induced hepatotoxicity Active in rat at a dose of 500 mg/kg Dried seed with inhibition of Glutathione (flavonoid enzyme increase depletion inhibition fraction) versus CCl4-Induced hepatotoxicity The dose used in n rat 200 mg/kg. Commercial The Barbiturate sample of hexobarbitol-indu potentiation seed ced sleeping time increased on days 1-7 Antibacterial (Bacillus subtilis, Escherichia coli, Dried seed Bacillus (EtOAc) megaterium, Staphylococcus aureus) Antifungal (Aspergillus niger) Dried seed (flavonoid fraction) Spasmolytic Dried seed (alkaloid fraction) Molluscicidal (Bulinus globosus) Dried seed (H2O) Reference Braide (1991a) Braide (1991b) In agar plate, it was active at Madubunyi a conc of 100 (1995) µg/ml In agar plate, it was active at Madubunyi a conc of 100 (1995) µg/ml Dried seed (EtOAc) Spasmolytic In vitro 55 Active in an ileum & duodenum of Guinea pig at a conc of 12.5 µg/ml vs Histamine-induce d contractions. Active in an ileum & duodenum of Guinea pig at a conc of 12.5 µg/ml vs Histamine-induce d contractions. Braide (1989) Braide (1989) Active against Okunji and Bulinus Iwu (1988) globosus at a 56 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Plant Part used Effects (Extracting In vivo species (Organism tested) (Country) solvent) Molluscicidal (Bulinus globosus) Dried seed (MeOH) Molluscicidal (Lymnaea natalensis) Dried seed (MeOH) Antidiarrheal Antiobesity Dietary intake Active in a male rat at a conc of Seeds 10% of diet vs castor oil-induced diarrhea. Active in a male rat at a conc of 20% of diet. Seeds Feeding for 6 weeks decreased body weight from 134 to 110 gm/rat The seed powder incooperated on animal feed was studied on serum levels of electrolytes and heavy metals on male albino rats. The pair-fed controls received Seed powder basal feed diet daily for six weeks. Results showed a significant (P< 0.05) dose dependent elevation of serum CI-, HCO3, Ca2+,Mg2+, Cu2+, Zn2+ and Mn2+ In vitro conc of 100 μg/ml Strong activity against Bulinus globosus at a conc of 100 μg/ml Strong activity against Lymnaea natalensis at a conc of 100 μg/ml Reference Okunji and Iwu (1988) Okunji and Iwu (1988) Okunji and Iwu (1988) Braide (1990) Agada and Braide (2009) Chapter 3 Pharmacological Activities of African Garcinia Plants Plant Part used Effects (Extracting In vivo species In vitro (Organism tested) (Country) solvent) Studied on mice with 10 mg/kg methamphetamine used to induce neurotoxicity and 200 mg/kg of extract was taken Kolanut orally. Results Hepatoprotective (H2O) indicated the serum levels of some of the marker enzymes and bilirubin to decrease significantly (P < 0.05). Antibacterial (Escherichia coli) G. kola (from DR Congo) Dried seed (CH2Cl2) Antimalarial (Plasmodium falciparum) Dried seed (EtOH) Antimalarial (Plasmodium falciparum) Dried stem bark (CH2Cl2) Antimalarial (Plasmodium falciparum) Dried stem bark (EtOH) Antiamebic (Entamoeba histolytica) Decoction Antibacterial (Klebsiella pneumoniae) Dried stem bark (Tannin fraction) Oze et al. (2010) Adegboye et al., (2008) Seed Antimalarial (Plasmodium falciparum) Reference Active against P. falciparum at a concentration of 6 μg/ml Active against P. falciparum at a concentration of 6 μg/ml Active against P. falciparum at a concentration of 6 μg/ml Active against P. falciparum at a concentration of 6 μg/ml Weak activity was observed at a MIC of 125 μg/ml Active at a concentration of 120 μg/ml Tona et al. (1999) Tona et al. (1999) Tona et al. (1999) Tona et al. (1999) Tona et al. (1999) Lutete (1994) 57 58 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Plant Effects species (Organism tested) (Country) Antibacterial (Citrobacter diversus) Spasmolytic G. Cytotoxicty livingstoneii (CA-HUMAN(from South COLON-CO-115) Africa) Cytotoxicty (CA-HUMANCOLON-CO-115) Part used (Extracting In vivo solvent) Dried stem bark (Tannin fraction) Active in the Ileum of Guinea pig at a conc of Dried trunk 0.2 mg/ml. bark Oberved 70.3% (Butanol reduction ext) incontraction vs KCl-Induced contractions Dried Leaf (MeOH) Dried root bark (CH2Cl2) Cytotoxicty Dried root (Human Cancer cell bark line HT 29) (CH2Cl2) Cytotoxicty (Human Cancer cell line, HT 620) Antitumor (CA-COLONSW 480) Dried root bark (CH2Cl2) Dried root bark (CH2Cl2) Antifungal (Cladosporium cucumerinum) Dried root bark (CH2Cl2) Anticrustacean (Artemia salina) Dried root bark (CH2Cl2) Molluscicidal (Biomphalaria glabrata) Dried root bark (CH2Cl2) Antifungal (Cladosporium cucumerinum) Dried root bark (CH2Cl2) G. Cytotoxicity (A549, Fruit livingstoneii DU145, KB and (Ethanol) In vitro Reference Active at a Lutete concentration (1994) of 95 μg/ml Kambu (1990) Inactive-the conc was not given Inactive-the conc was not given In a cell culture, it was active with IC50 value of 10.0 µg /ml Active with IC50 value of 8.0 µg /ml Active with IC50 value of 8.0 µg /ml Active- at a concentration of 100 µg/plate Active- with LC50 value of 17.0 µg /plate Seen inactive at a concentration of 400 ppm Active- at a concentration of 100 µg/plate Active with an average CC50 Chapuis et al. (1988) Sordat-Dise rens et al. (1992) Sordat-Dise rens et al. (1992) Sordat-Dise rens et al. (1992) Sordat-Dise rens et al. (1992) Sordat-Dise rens et al. (1992) Cepleanu et al. (1994) Cepleanu et al. (1994) Cepleanu et al. (1994) Magadula and Chapter 3 Pharmacological Activities of African Garcinia Plants Plant Part used Effects (Extracting In vivo species (Organism tested) (Country) solvent) (from Kbivin) Tanzania) Antiviral (HIV-1 viral replication in MT4 cells) Fruit (Ethanol) Antimicrobial (E. G. lucida coli, P. aeruginosa, Stem bark (from S. typhi, S. aureus, (Methanol) Cameroon) C. albicans). Stem bark G. lucida Tripanosomal (T. b. (1:1 (from brucei) CH2Cl2:Me Cameroon) OH mixture) In vitro Reference value of 5.7-12.0 µg/ml Inhibited the HIV-1 viral replication of MT4 cells with EC50 value of 2.25 µg/mL) Active only to C. albicans with MIC value of 64 μg/mL Suleiman (2010) Magadula and Suleiman (2010) Momo et al. (2011) Activity value Fotie at al. at IC50 4.9 (2007) μg/mL) Crude extract (100 μg/mL) was able to clear the parasites (100% inhibition) In a 1:1 conc under cell culture, it was reported to be active but the conc was not given G. lucida Antileishmanial (from (promastigote L. Cameroon) donovani) Stem bark (1:1 CH2Cl2:Me OH mixture) G. ovalifolia (from Central African Republic) Antiviral (Virus-HIV) Dried Leaf (CHCl3-Me OH) G. ovalifolia (from Togo) Antiyeast (Candida Dried Stem albicans) bark (EtOH) Inactive at a Kpakote et concentration al. (1998) of 4.0 mg/ml Antibacterial (Staphylococcus aureus) Antibacterial (Pseudomonas aeruginosa) Antifungal (Aspergillus fumigatus) Active at a concentration of 4.0 mg/ml Inactive at a concentration of 4.0 mg/ml Active at a concentration of 4.0 mg/ml Dried Stem bark (EtOH) Dried Stem bark (EtOH) Dried Stem bark (EtOH) 59 Fotie at al. (2007) Gustafson et al. (1992) Kpakote et al. (1998) Kpakote et al. (1998) Kpakote et al. (1998) 60 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Plant species (Country) G. polyantha (from Togo) G. verrucosa ssp orientalis (from Madagascar ) Part used Effects (Extracting In vivo (Organism tested) solvent) G. semseii (from Tanzania) Cytotoxicity (A549, Fruit DU145, KB and (Ethanol) Kbivin) Antifungal (Aspergillus fumigatus) Cytotoxicity (Murine P388 cell line) Antiviral (HIV-1 viral replication in MT4 cells) G. volkensii Antimicrobial, (from antioxidant and Tanzania) Cytotoxicity In vitro Dried Stem bark (EtOH) Stem bark (EtOAc) Fruit hulls (Ethanol) Stem bark (Ethanol) Reference Kpakote et al. (1998) Exhibited 99 % inhibition of the P388 cell growth at a concentration of 10 μg/ml Active with CC50 value range of 7.8-9.1 µg/mL) Inhibited the HIV-1 viral replication of MT4 cells with EC50 value of 0.93 µg/mL) Antibacterial activity with MIC values ranging of 0.049->2.50 mg/ml. The BST exhibited LC50 value >100 μg/ml. Rajaonarive lo et al. (2009) Magadula and Suleiman (2010) Magadula and Suleiman (2010) Mbwambo et al. (2011) 3.3 Antimalarial Activity Malaria is one of the most serious protozoal diseases in man and ranks number one in terms of morbidity in the tropical countries. It is estimated that at least 40% of the world's population live in endemic areas, among which 90% are distributed in Africa south of Sahara desert (Bruce-Chwatt et al., 1981). The use of plant secondary metabolites as a cure and/or leads for the development of Chapter 3 Pharmacological Activities of African Garcinia Plants 61 potential antimalarial compounds is a well known approach (Philipson and Wright, 1990). Currently many medicinal plants, including Garcinia plants from Africa have been investigated in vitro and/or in vivo testing for their potential antimalarials. Tona and co-workers investigated 20 extracts from different parts of some African medicinal plants used in Congolese traditional medicine for the treatment of malaria. Of these, the dichloromethane and ethanol extracts of the dried seeds of G. kola exhibited more than 60% inhibition of the Plasmodiun falciparum growth in vitro at a test concentration of 6 μg/ml (Tona et al., 1999), (Table 4). In another study from G. polyantha, which is an important medicinal plant of Cameroonian traditional medicine, phytochemical analysis of its different parts gave xanthones, flavonoids, benzophenones and triterpenoids (Lannang et al., 2008). The isolated compounds were tested for their in vitro antimalarial potential. In this assay, only isoxanthochymol (13) showed strong chemosuppression of P. falciparum when tested in vitro (Lannang et al., 2008). In a study from G. livingstoneii, a series of xanthones and flavonoids was isolated and tested for antiparasitic activity against P. falciparum. One of the isolates, a biflavonoid ent-naringeninyl-(I-3α,II-8)-4'-O-methylnaringenin (14), showed a remarkable in vitro activity against P. falciparum with the IC50 value of 6.0 μg/ml (Mbwambo et al., 2006). Other xanthones and biflavonoids isolated from this plant were not active in this assay. 3.4 Anticancer Activity Cancer is rapidly becoming a major health problem with a global burden of about 8 million deaths worldwide (WHO, 2007). This problem is correlated 62 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies with the emergence of HIV/AIDS, in which malignancies occur as part of opportunistic diseases due to depressed immune system and other life styles. Since many people in Africa live in rural areas, treatment of cancer-related illnesses has mostly involved plant extracts, since most of people can not afford the costs of currently available anticancer drugs. This necessitates the need for continued search for anticancer compounds from medicinal plants. Currently, several anticancer extracts and compounds from African Garcinia plants have been characterized and their activities against different types of human cancer cell-lines established (Rajaonarivelo et al., 2009; Magadula & Suleiman, 2010; Mbwambo et al., 2006). A recent study from Garcinia plants collected in Tanzania; reported the evaluation of ethanol extracts for their in vitro cytotoxicity against four human cancer cell lines. Among the tested extracts, the fruit extract of G. livingstoneii and fruit hulls of G. semseii showed moderate to mild cytotoxic activities against A549, DU145, KB and Kbivin human cell lines, with 50 % cytotoxic (CC50) values ranging from 5.7-20.0 µg/ml (Magadula and Suleiman, 2010), whereby taxol was used as a positive control. Rajaonarivelo and co-workers investigated the cytotoxicity of the ethyl acetate extract of the stem bark of G. verrucosa ssp orientalis, collected from the Eastern rain forest of Madagascar. In this study the EtOAc extract exhibited 99 % in vitro inhibition of the P388 cell growth at a concentration of 10 μg/ml (Rajaonarivelo et al., 2009). In another study on anticancer activity, a dichloromethane extract of the root bark of G. livingstoneii; collected in South Africa exhibited in vitro growth inhibitory activities against four human colon carcinoma cell lines. The human cell lines tested were CO 115, SW 480, SW 620 and HT 29 with the IC50 values of 10, 8, 8 and 10 μg/ml, respectively (Sordat-Diserens et al., 1992). Chapter 3 Pharmacological Activities of African Garcinia Plants 63 Flavonoids possess various pharmacological properties including anticancer activities (Iriti and Varoni, 2013). Two anticancer flavonoids have been reported from the leaves of G. livingstoneii, namely; amentoflavone (1) and 4''-methoxy amentoflavone (2) (Kaikabo et al., 2009). The cytotoxicity of these compounds was assessed using Vero monkey kidney cells. The authors showed low toxicity against the cell line with LD50 values of 386 μg/ml and >600 μg/ml, respectively (Kaikabo et al., 2009). In this test, berberine (CC50 = 170 μg/ml) was used as a positive control. In a different study from the root bark of G. livingstoneii, two dimeric xanthones, garcilivins A (15) and C (16) were isolated and tested for in vitro cytotoxicity against MRC-5 cells. Compound 15 showed a higher and nonselective cytotoxicity (IC50 = 2.0 μg/ml), than its diastereoisomer, compound 16 (IC50 = 52.3 μg/ml) (Mbwambo et al., 2006). Further investigation from the root bark of G. livingstoneii gave two xanthones, 6,11-dihydroxy-2,2-dimethyl-pyrano[3,2-c]xanthone (17) and 4- (3’, 7’dimethylocta-2’, 6’-dienyl)-1,3,5-trihydroxy-9H-xanthone (18). These compounds inhibited the growth of SW 480 and CO 115 human colon carcinoma cells with compound 18 (IC50 = 0.6 μg/ml) showing comparable activity to the synthetic drug, 5-fluorouracil (IC50 = 0.4 μg/ml) (Sordat-Diserens et al., 1992). The bioassay-guided fractionation of the EtOAc extract of the stem bark of G. verrucosa led to the isolation of a new cytotoxic polycyclic prenylated acylphloroglucinol, named garcicosin (19). This compound was observed to inhibit P388 cell growth at a concentration of 10 μg/ml with an IC50 value of 3.0 μg/ml. (Rajaonarivelo et al., 2009). The study by Dibwe and co-workers on the chloroform extract of Garcinia huillensis indicated a preferential cytotoxicity (PC50 = 17.8 µg/mL) against human pancreatic cancer PANC‐1 cells under nutrient‐deprived conditions. 64 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Further investigation of the active constituents revealed 12 known anthraquinones together with a damnacanthal (20). Compound 20 caused preferential necrotic cell death of PANC‐1 and PSN‐1 cells under nutrient‐deprived and serum‐sensitive conditions of PC50 = 4.46 µm and 3.77 µm, respectively (Dibwe et al., 2012). 3.5 Antioxidant Activity Antioxidants such as dietary flavonoids work by scavenging free radicals, chelation of metal ions, and decomposition of peroxides such as lipid peroxides (Dufresne and Farnsworth, 2001). It is well established that; phenolic compounds are known to be antioxidants with excellent hydrogen or electron donor capacity (Chiang et al., 2003). It has been suggested that the antioxidant effect of Garcinia plants is ascribed mostly to biflavonoids (Farombi et al., 2002). Thus, they are thought to play important role in the prevention of various human disorders as free radical scavengers. Garcinia kola, a tropical plant which grows in moist forest, has found to have many applications in traditional medicine, especially in the West and Central African sub-region. This plant is the highly investigated among all Garcinia species growing in Africa. Farombi and co-workers investigated the antioxidant and scavenging properties of a flavonoid extract of G. kola seeds. The in vitro assay involved the free radicals and reactive oxygen species from which the flavonoid extract, commonly known as kolaviron, exhibited noticeably reducing power and antioxidant activity by inhibiting the peroxidation of linoleic acid. It further exhibited 57% scavenging effect on superoxide at a concentration of 1 mg/ml and 85% scavenging activity on hydrogen peroxide at a concentration of 1.5 µg/ml. Similarly, flavonoid extract, at a concentration of 2 mg/ml, showed a 89% scavenging effect on a,a-diphenylb-picrylhydrazyl radical (DPPH), Chapter 3 Pharmacological Activities of African Garcinia Plants 65 indicating that the extract has effective activities as a hydrogen donor and as a primary antioxidant to react with lipid radicals (Farombi et al., 2002). The protective effects of kolaviron, a Garcinia biflavonoid extract from the seeds of G. kola widely consumed in some West African countries, was tested against oxidative damage to molecular targets ex-vivo and in vitro. Treatment with hydrogen peroxide (H2O2) at a concentration of 100 μg/ml increased the levels of DNA strand breaks and oxidized purine and pyrimidine bases in both human lymphocytes and rat liver cells using alkaline single cell gel electrophoresis (COMET assay). Kolaviron was protective at concentrations between 30-90 μg/ml and decreased H2O2-induced DNA strand breaks and oxidized bases (Farombi et al., 2004). Furthermore, kolaviron exhibited protective effects against oxidative damage to molecular targets via scavenging of free radicals and iron binding (Farombi et al., 2004). In another study by Farombi and co-workers, the antioxidant and radical scavenging activities were investigated from the flavonoid fraction of the seeds of G. kola. The extract was fed to the male rats for six weeks and their body weights decreased from 134 to 110 gm/rat (Table 3) (Farombi et al., 2002). Further studies from the seeds of G. kola indicated the methanolic extract to show many activities. Methanol extract was subjected to column chromatography under silica gel to give five fractions, and each fraction was tested for the free radical scavenging activities and antioxidant potentials for various in vitro models (Okoko, 2009). Results indicated that the fourth fraction possessed the highest antioxidant and radical scavenging activities as compared with the rest of fractions. It was also established that the fourth fraction strongly inhibited nitric oxide production in lipopolysaccharide activated macrophage U937 cells (Okoko, 2009). The CH2Cl2/MeOH (1:1) extract of the stem bark of G. afzelii was found to exhibit significant anti-oxidant effects, based on the scavenging of the stable DPPH free radical showing the IC50 value of 20.5 66 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies μg/100 ml (Waffo et al., 2006). Two novel prenylated xanthones, afzeliixanthones A (21) and B (22), were isolated and tested for their antioxidative properties. The two compounds showed high antioxidant activity with the IC50 values of 17.7 and 14.0 μg/100 ml comparable to α-tocopherol (23) (IC50 13.5 μg/100 ml) as a standard (Waffo et al., 2006). In another study by Okoko on the methanol extract of the seeds of G. kola, column chromatographic fractionation under silica gel and spectroscopic analysis of the active fraction revealed the presence of four compounds namely garcinia biflavonoids GB1 (3) and GB2 (24), garcinal (25) and garcinoic acid (26). These four compounds were reported to be responsible for the great antioxidant potential of Garcinia kola seeds (Okoko, 2009). Further work by Terashima and co-workers investigated the structure-antioxidative activity relationships of derivatives based on garcinoic acid (26) from Garcinia kola, which led to the discovery of a powerful antioxidative agent of a chromen moiety (compound 27) that showed activity of 18.7 higher than standard compound, 23 (Terashima et al., 2002). Chapter 3 Pharmacological Activities of African Garcinia Plants 67 OH HO OH HO O O O OH OH O O HO O OH 13 OH OH O O OH OH OH O O OH O 15 beta-H 16 alpha-H OH O O R O O 14 R OH O OH O O O OH OCH3 CHO i-Pr OH 18 17 O OCH3 O HO 15 OH HO O OH O O 21 20 19 O OCH3 CH3 H3CO HO O OH OH H3C O CH3 22 23 CH3 O OH HO O HO OH OH O HO O O 25 R CHO 26 COOH CH3 O OH OH OH R HO 27 24 Fig. 20. Structures of bioactive compounds isolated from some African Garcinia plants (Cont). 68 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Phytochemical analysis from the chloroform extract of the stem bark of G. polyantha resulted in the isolation of four prenylated xanthones, bangangxanthones A (28) and B (29), 1,5-dihydroxyxanthone (30) and 2-hydroxy-1,7-dimethoxyxanthone (31) that were screened for DPPH radical scavenging activity (Lannang et al., 2005). Compound 28 showed significant activity with IC50 value of 87.0 μg/ml relative to the standard, 3-t-butyl-4-hydroxyanisole (IC50 = 42.0 μg/ml). Likewise, compound 29 showed weak activity with IC50 of 482.0 μg/ml, while compounds 30 and 31 showed 47.8% and 39.5% of inhibition respectively, at the concentration of 1 μg/ml (Lannang et al., 2005). In the search for antioxidant compounds from G. buchananii, Stark et al. (2012), isolated and identified three 3,8″-linked biflavanones and two flavanone-C-glycosides biflavonoids using hydrogen peroxide scavenging and oxygen radical absorbance capacity (ORAC) assays. The compounds included a biflavanone GB-2 (24), manniflavanone (32), taxifolin- 6- C- β- Dglucopyranoside (33), aromadendrin-6-C-β-D-glucopyranoside (34) and buchananiflavanone (35). Manniflavanone (32) and GB-2 (24) showed high H₂O₂ scavenging activity with EC₅₀ values of 2.8 and 2.2 μM, respectively and the ORAC activities of 13.73 and 12.10 μmol TE/ μmol, respectively, (Stark et al., 2012). 3.6 Antiviral Activity In the absence of a vaccine and efficient treatment, HIV/AIDS continues to be a growing public health problem in the world. The rising number of HIV/AIDS cases in Africa has raised the demand for medical care and consequently has created a burden to the available limited health budgets. Chapter 3 Pharmacological Activities of African Garcinia Plants 69 Consequently, this has raised the interest of screening crude plant extracts for anti-HIV activity, while little research has been done on pure compounds. Two Garcinia plants growing in Tanzania has been evaluated for their in vitro anti-HIV activity against HIV-1 viral replication in MT4 cells. The ethanol extracts of the fruits of G. livingstonei and G. semseii revealed significant anti-HIV-1 activity with EC50 values of 2.25 ± 0.51 and 0.93 ± 0.67 µg/mL respectively (Magadula & Suleiman, 2010). Furthermore, another study from ethanol extracts of some Garcinia species collected in Tanzania were investigated for their HIV-1 protease (HIV-1 PR) inhibitory activities using high performance liquid chromatography (HPLC). Among the tested extracts, the fruit hulls of G. semseii showed the most potent inhibitory activity against HIV-1 PR with an IC50 value of 5.7 μg/ml, followed by the stem bark extracts of G. edulis and G. kingaensis with IC50 values of 9.2 and 15.2 μg/ml, respectively (Magadula & Tewtrakul, 2010). In another study, the chloroform-methanol (1:1) extract of the dried leaf of G. ovalifolia, collected from Central African Republic, showed significant anti-HIV activity when tested in vitro (Gustafson et al., 1992). Benzophenones are phenolic compounds which are reported to display antiviral activity. For instance, a polyisoprenylated benzophenone, guttiferone A (36) isolated from the fruits of G. livingstonei was found to inhibit the cytopathic effects in human lymphoblastoid CEM-SS cells in vitro, with EC50 values of ≤ 10 μg/ml (Gustafson et al., 1992). Phytochemical investigation of the root bark of G. edulis gave a new isoprenylated xanthone, 1, 4, 6-trihydroxy -3-methoxy-2- (3-methyl-2-butenyl)-5-(1,1-dimethyl-prop-2-enyl)xanthone (37) that showed significant in vitro anti-HIV-1 protease activity with IC50 value of 11.3 μg/ml (Magadula, 2010). 70 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies OH O OH O OH O O OH O O O OH OH 28 OH OH 30 29 OH OH OH O H3CO OH O OH OH OH O HO 31 R1 R2 OH OH O O HO O HO OCH3 O 33 OH R1 R2 glucose 34 H glucose O OH R OH O 32 35 R OH H OH HO HO O HO O OCH3 OH O O 36 37 Fig. 20. Structures of bioactive compounds isolated from some African Garcinia plants (Cont). 3.6 Other Biological Activities The phytochemical study on the methanol extract of the wood trunk of G. polyantha, gave a series of oxygenated xanthones that were screened for their anticholinesterase potentials on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes (Louh et al., 2008). Polyanxanthones A-C (38-40), 1,3,5-trihydroxyxanthone (41), 1,5-dihydroxyxanthone (30) and 1,6-dihydroxy-5-methoxyxanthone (42) showed noteworthy inhibitory activities. Compounds 30, 40 and 41 showed significant inhibition against BChE with an Chapter 3 Pharmacological Activities of African Garcinia Plants 71 IC50 value of 93.0, 2.54 and 74.4 μg/ml, respectively, while compound 39 showed significant inhibition against both AChE (IC50 = 46.3 μg/ml) and BChE (IC50 = 25.5 μg/ml) compared to the standard, galantamine (IC50 = 0.5 and 8.5 μg/ml, respectively). Compound 38 indicated 41.8% and 7.0% inhibition against AChE and BChE, respectively, at the concentration of 0.2 mg/ml (Louh et al., 2008). Kolaviron, the predominant constituent in G. kola, is a biflavonoid complex [containing biflavanones GB-1 (3) and GB-2 (24) and kolaflavanone (43)] that has been reported to prevent hepatotoxicity mediated by several toxins (Iwu et al., 1987). Similarly, kolaviron exhibited hypoglycemic effects in normal and alloxan- and streptozotocin-induced diabetic animals (Adaramoye et al., 2006). In another study for kolaviron, the protein expression levels of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) were evaluated by western blotting, while DNA-binding activities of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) were determined by electrophoretic mobility shift assay. The results indicated kolaviron to have an ability to inhibit COX-2 and iNOS expression through down regulation of NF-κB and AP-1 DNA binding activities, which could be a mechanism for the hepatoprotective properties of kolaviron (Farombi et al., 2009). In the study by Balemba and co-workers, the stem bark of G. buchananii inhibited propulsive motility and fast synaptic potentials in the guinea pig distal colon. The result indicated a concentration-dependent manner, with an optimal concentration of about 10 mg/ ml. In this study, no any active principle was isolated from the active fractions (Balemba et al., 2010). Further study from the same plant investigated the potential of the constituents on reducing gastrointestinal peristaltic activity via 5-HT(3) and 5-HT(4) receptors. Phytochemical screening of the crude extract indicated the presence of 72 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies flavonoids, steroids, alkaloids, tannins and phenols. The results revealed that the anti-motility effects of the aqueous extract of G. buchananii are significantlly mediated by compounds that affect 5-HT(3) and 5-HT(4) receptors. However, no single compound was characterized or identified from the active components (Boakye et al., 2012). Furthermore, the G. buchananii extract and its anti-motility fractions were studied to be effective remedies against lactose-induced diarrhea. Results indicated that the active extract contained compounds that are responsible for reducing the body weight and supporting the upward intake of food and water (Boakye et al., 2012). Depsidones isolated from Garcinia plants are reported to possess many biological activities (Ito et al., 2001). In a phytochemical study from the stem bark of G. brevipedicellata collected in Cameroon, four new depsidones named brevipsidones A-D (44-47) were isolated and evaluated for their possible glycosidase enzyme inhibitory activity against α-glucosidase. These compounds showed moderate α-glucosidase inhibition with IC50 values of 21.2, 27.8, 59.6 and 7.04 μg/ml respectively (Ngoupayo et al., 2008). The crude extract of the stem bark of the G. lucida indicated a significant trypanocidal and antileishmanial activities. The bioassay guided isolation of the constituents of the benzo[c]phenanthridine stem bark alkaloids, led to the isolation dihydrochelerythrine of (48), three 6- acetonyldihydrochelerythrine (49) and lucidamine A (50). The isolated compounds as well as the crude extract displayed poweful antiprotozoal activity against Trypanosoma brucei brucei and Leishmania donovani, with little toxicity to Vero cells and the host cells (Fotie et al., 2007). The crude extract of G. lucida displayed significant activity against T. b. brucei (IC50 4.9 μg/mL) with no toxicity on the Vero cell. The isolated compounds, the dihydrochelerythrine derivatives (48-50) exhibited interesting activity, with IC50 Chapter 3 Pharmacological Activities of African Garcinia Plants 73 values in the range 0.8–14.1 μM. Dihydrochelerythrine (48) was the most potent compound (IC50 0.8 μM), with more than 44-fold selectivity for T. b. brucei parasites over Vero cells (Fotie et al., 2007). When tested on promastigote L. donovani, the crude extract (100 μg/mL) and compounds 48-50 (100 μM) were able to clear the parasites (100% inhibition), whereas at 10 μM, these compounds achieved about 89, 87, and 76% inhibition, respectively. Phytochemistry of African Garcinia Plants 76 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies 4.1 Introduction Many African countries are endowed with tropical forests that are rich in the diversity of plants. These plants constitute a rich, but largely untapped pool of natural products as chemicals with potential socio-economic benefits. Given that the occurrence of many secondary metabolites is genus or species specific, probability is high that many plants contains potentially useful biological properties that will remain undiscovered, unidentified and unused; this is a true case for tropical African rain forests. Presently, many medicinal plants, including Garcinia plants, are threatened with extinction or severe genetic loss, while their detailed scientific information is still lacking. Hence, a continued and sustainable biological and chemical investigation of these useful plants is needed. From the Garcina plants growing in Africa, more than 130 secondary metabolites have been isolated, with benzophenones, flavonoids, triterpenoids and xanthones being the major constituents (Table 5). Furthermore, about 18 other compounds have been reported from African Garcinia species. From all the African Garcinia plants, the most well-known and phytochemically studied is G. kola which is reported to grow in almost all West and Central African countries (Iwu et al., 1990, Madubunyi, 1995, Okunji & Iwu, 1991, Kapadia et al., 1994). However, these phytochemical reports still indicate that only a small fraction of African Garcinia plants have been studied for their chemical constituents. This necessitates further work to be done for an uninvestigated species. Chapter 4 Phytochemistry of African Garcinia Plants 77 Table 5. Compounds isolated from the African Garcinia species. Class Name Plant species Part Where Reference collected Garcinol (51) G. huillensis Stem bark Cameroon Xanthochymol (52) G. staudtii Stem bark Nigeria G. mannii Stem, leaves Cameroon & seeds G. polyantha Stem bark Cameroon Semsinone A (53) G. semseii Stem bark Tanzania Semsinone B (54) G. semseii Stem bark Tanzania Semsinone C (55) G. semseii Stem bark Tanzania G. semseii G. semseii G. livingstoneii Fruit hulls Fruit hulls Tanzania Tanzania Fruit Tanzania Guttiferone E (57) G. ovalifolia Leaf CAR Isoxanthochymol (13) G. ovalifolia Leaf CAR Benzophen Guttiferone K (56) ones Guttiferone A (36) Kolanone (58) Biflavanone GB-1 (3) G. polyantha Stem bark Cameroon G. polyantha Root bark Cameroon G. kola Fruit pulp Nigeria G. kola Dried root Nigeria G. kola Dried seed Nigeria G. buchananii Heartwood Uganda Jackson et al. (1971) Cameroon Hussain and Waterman (1982) G. kola Leaf, Seed, Stem bark, heartwood Dried seed G. kola Stem bark, G. kola Root bark G. mannii Flavonoids Bakana et al. (1987) Waterman and Hussain (1982) Hussain and Waterman (1982) Ampofo et al. (1986) Magadula et al. (2008) Magadula et al. (2008) Magadula et al. (2008) Magadula (2012) Magadula (2012) Gustafson et al. (1992) Gustafson et al. (1992) Gustafson et al. (1992) Ampofo et al. (1986) Lannang et al. (2008) Hussain et al. (1982) Iwu et al. (1990) Madubunyi (1995) Biflavanone GB-2 (24) G. buchananii Heartwood Nigeria DR Congo Nigeria Uganda Iwu (1985) Kabangu et al. (1987) Han et al. (2005) Jackson et al. (1971) 78 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Class Name Plant species Part G. kola Leaf, Seed, Stem bark, heartwood Dried seed G. kola Stem bark, G. kola Dried stem Nigeria G. buchananii Heartwood Uganda G. mannii Biflavanone GB-1A (59) Biflavanone GB-1B (60) Biflavanone GB-2A (61) Cyanidin (62) Eriodictyol (63) Where Reference collected Cameroon Nigeria DR Congo G. mannii Leaf, Seed, Stem bark, heartwood Cameroon G. volkensii Heartwood Kenya G. kola Dried stem Nigeria G. kola Dried stem Nigeria G. buchananii Heartwood Uganda G. mannii Leaf, Seed, Stem bark, heartwood Cameroon G. volkensii Heartwood Kenya G. kola Dried stem Nigeria G. Stem & seed Cameroon chromocarpa Stem, seed & G. conrauana Cameroon leaf Fukugetin (64) G. conrauana Heartwood Cameroon O-Methylfukugetin (65) G. conrauana Stem, heartwood Cameroon G. quadrifaria Stem bark Cameroon G. densivenia Stem bark Cameroon Manniflavanone (32) G. mannii G. kola Seed, Leaf, Stem bark, heartwood Dried root G. conrauana Leaves Morelloflavone G. mannii Heartwood Cameroon Nigeria Hussain and Waterman (1982) Iwu (1985) Kabangu et al. (1987) Terashima et al. (1999a) Jackson et al. (1971) Hussain and Waterman (1982) Herbin et al. (1970) Terashima et al. (1999a) Terashima et al. (1999a) Jackson et al. (1971) Hussain and Waterman (1982) Herbin et al. (1970) Terashima et al. (1999a) Gartlan et al. (1980) Hussain and Waterman (1982) Hussain and Waterman (1982) Hussain and Waterman (1982) Waterman and Hussain (1982) Waterman and Crichton (1980) Hussain and Waterman (1982) Iwu et al. (1990) Hussain and Cameroon Waterman (1982) Cameroon Hussain and Chapter 4 Phytochemistry of African Garcinia Plants Class Name Stem bark Where Reference collected Waterman (1982) Mbafor et al. Cameroon (1989) Tanzania Stark et al. (2012) Stem bark Tanzania Stark et al. (2012) Stem bark Tanzania Stark et al. (2012) Root bark Tanzania G. volkensii Stem bark Tanzania G. livingstoneii Root bark Tanzania Plant species Part glycoside (66) Taxifolin-6-C-β-D-gluc G. epunctata opyranoside (33) G. buchananii Aromadendrin-6-C-β-D G. buchananii -glucopyranoside (34) Buchananiflavanone G. buchananii (35) G. Volkensiflavone (67) livingstoneii Morelloflavone (68) Garcinia biflavanone GB-2 (24) Amentoflavone (1) Stem bark G. quadrifaria Stem bark Cameroon G. densivenia Stem bark Cameroon G. volkensii Heartwood Kenya G. volkensii Stem bark Tanzania Stem bark Cameroon Root bark Tanzania Root bark Dried Seed Nigeria Nigeria G. kola Dried Seed Nigeria G. kola Dried seed Nigeria G. kola Dried seed Nigeria G. kola Dried seed Nigeria G. kola Dried seed Nigeria G. kola Dried seed Nigeria G. kola Dried seed Nigeria G. kola Dried seed Nigeria G. kola Dried stem Nigeria G. Leaf South ent-Naringeninyl-(I-3α, II-8)-4'-O-methylnaring G. quadrifaria enin (14) G. livingstoneii Kolaflavanone (43) G. kola G. kola Garcinia biflavanone GB-1 (3) 79 Mbwambo et al. (2006) Mbwambo et al. (2011) Mbwambo et al. (2006) Waterman and Hussain (1982) Waterman and Crichton (1980) Herbin et al. (1970) Mbwambo et al. (2011) Waterman and Hussain (1982) Mbwambo et al. (2006) Iwu et al. (1990) Iwu (1985) Kapadia et al. (1994) Okunji & Iwu (1991) Iwu and Igboko (1982) Iwu et al. (1987) Madubunyi (1995) Okunji and Iwu (1991) Iwu et al. (1987) Madubunyi (1995) Terashima et al. (1999a) Kaikabo et al. 80 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Class Name Plant species Part livingstoneii 4''-Methoxyamentoflav G. one (2) livingstoneii Where collected Africa South Africa Reference Apigenin (71) G. nervosa Dried leaf Nigeria 3,8''-Biapigenin (72) G. nervosa Dried leaf Nigeria Nervosin (73) Irigenin (74) 7-Methyltectorigenin (75) I-5, II-5 I-7,II-7,I-3’,I-4’, II-4’-Heptahydroxy-[I3, II-8]-flavanonylflavone flavanoylflavone (76) I-3, II-3, I-5, II-5, I-7, II-7, I-4',II-4'-Octahydroxy [I-2', II-2'] biflavone (77) G. nervosa G. nervosa Dried leaf Dried leaf Nigeria Nigeria (2009) Kaikabo et al. (2009) Iwu and Igboko (1982) Terashima et al. (1995) Terashima et al. (1997) Kapadia et al. (1994) Kapadia et al. (1994) Parveen et al. (2004) Parveen et al. (2004) Ilyas et al. (1994) Ilyas et al. (1994) G. nervosa Dried leaf Nigeria Ilyas et al. (1994) G. nervosa Dried leaf Nigeria Babu et al. (1988) G. nervosa Dried leaf Nigeria Parveen et al. (2004) Quercetin (78) G. nervosa Dried leaf Nigeria Taxifolin (79) G. buchananii Stem bark Parveen et al. (2004) Tanzania Stark et al. (2012) Friedelin (80) G. ovalifolia Stem bark Cameroon G. polyantha Stem bark Cameroon G. edulis Root bark Tanzania G. lucida Stem bark Cameroon G. polyantha Stem bark Cameroon G. lucida Cameroon Leaf Acacetin (69) G. kola Seed Nigeria Garcinianin (70) G. kola Dried stem Nigeria G. kola Dried seed Nigeria Dried seed Nigeria Dried seed Nigeria Kolabiflavonoid GB-1 G. kola (3) Kolabiflavonoid GB-2 G. kola (24) Triterpenoi ds Oleanolic acid (81) Stem bark Waterman et al. (1980) Lannang et al. (2005) Magadula (2010) Momo et al. (2011) Lannang et al. (2005) Momo et al. Chapter 4 Phytochemistry of African Garcinia Plants Class Name Plant species Part Lupeol (82) G. polyantha Stem bark Where Reference collected (2011) Lannang et al. Cameroon (2005) Tanzania Magadula (2010) Magadula et al. Tanzania (2008) Tanzania Magadula (2010) Lannang et al. Cameroon (2008) Lannang et al. Cameroon (2008) Cameroon Fotie et al. (2007) Momo et al. Cameroon (2011) Momo et al. Cameroon (2011) Momo et al. Cameroon (2011) G. edulis Root bark Achilleol A (83) G. semseii Stem bark Lupeol acetate (84) G. edulis Root bark Garcinane (85) G. polyantha Root bark Magnificol (86) G. polyantha Root bark Betulinic acid (87) G. lucida Stem bark G. lucida Stem bark Putranjivic acid (88) G. lucida Stem bark Methyl putranjivate (89) G. lucida Stem bark Smeathxanthone A (10) G. Stembark smeathmannii Cameroon G. polyantha Root bark Cameroon G. Stembark smeathmannii Cameroon G. polyantha Root bark Cameroon Smeathxanthone B (11) 1,3,5-Trihydroxyxantho G. ne (41) smeathmannii G. polyantha 1,3-dihydroxyxanthone G. smeathmannii (90) Xanthones G. polyantha Rheediaxanthone (91) Rheediaxanthone A (92) Bangangxanthone A (28) Bangangxanthone B (29) 1,5-Dihydroxyxanthone (30) Stembark Cameroon Wood trunk Cameroon Stembark 81 Cameroon Wood trunk Cameroon G. staudtii Stembark Nigeria G. staudtii Stembark Nigeria G. polyantha Stem bark Cameroon G. polyantha Stem bark Cameroon G. polyantha Stem bark Cameroon G. afzelii Stem bark Cameroon 2-Hydroxy-1,7-dimetho G. polyantha Stem bark Cameroon Komguem et al. (2005) Lannang et al. (2008) Komguem et al. (2005) Lannang et al. (2008) Komguem et al. (2005) Louh et al. (2008) Komguem et al. (2005) Louh et al. (2008) Waterman and Hussain (1982) Waterman and Hussain (1982) Lannang et al. (2005) Lannang et al. (2005) Lannang et al. (2005) Waffo et al. (2006) Lannang et al. 82 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Class Name Plant species Part xyxanthone (31) 1,4,5-Trihydroxy-3-(3G. methylbut-2-enyl)-9Hlivingstoneii xanthen-9-one (7) G. livingstoneii 6,11-Dihydroxy-3-meth yl-3-(4-methylpent-3-e G. nyl)pyrano[2,3-c]xanth livingstoneii one (8) G. livingstoneii 4[(E)-3,7-Dimethylocta -2,6-dienyl]-1,3,5-trihy G. droxy-9H-xanthen-9-on livingstoneii e (9) G. Garcilivin A (15) livingstoneii G. livingstoneii G. Garcilivin B (93) livingstoneii G. livingstoneii G. Garcilivin C (16) livingstoneii G. livingstoneii Root bark Tanzania Mbwambo et al. (2006) Root bark South Africa Sordat-Diserens et al. (1992) Root bark Tanzania Mbwambo et al. (2006) Root bark South Africa Sordat-Diserens et al. (1992) Root bark Tanzania Mbwambo et al. (2006) Root bark Tanzania Root bark South Africa Root bark Tanzania Root bark South Africa Root bark Tanzania Root bark South Africa Stem bark Cameroon G. afzelii Stem bark Cameroon G. afzelii Stem bark Cameroon G. afzelii Stem bark Cameroon G. polyantha Stem bark Cameroon Afzeliixanthone A (21) G. afzelii Afzeliixanthone A B (22) 1,7-Dihydroxyxanthone (94) 1,3,7-Trihydroxy-2-(3methylbut-2-enyl)xanth one (95) Rheediaxanthone-B (96) Isorheediaxanthone-B (97) 12b-Hydroxy-des-D-ga rcigerrin A (6) 6,11-Dihydroxy-2,2-di methyl-pyrano[3,2-c]xa nthone (17) 4-(3’,7’-Dimethylocta- Where Reference collected (2005) G. polyantha Stem bark Mbwambo et al. (2006) Sordat-Diserens et al. (1992) Mbwambo et al. (2006) Sordat-Diserens et al. (1992) Mbwambo et al. (2006) Sordat-Diserens et al. (1992) Waffo et al. (2006) Waffo et al. (2006) Waffo et al. (2006) Waffo et al. (2006) Ampofo et al. (1986) Ampofo et al. Cameroon (1986) South Sordat-Diserens Africa et al. (1992) G. livingstoneii Root bark G. livingstoneii Root bark South Africa Sordat-Diserens et al. (1992) G. Root bark South Sordat-Diserens Chapter 4 Phytochemistry of African Garcinia Plants Class Name Plant species Part 2’, 6’-dienyl) livingstoneii -1,3,5-trihydroxy -9Hxanthone (18) Garcigerrin A (4) G. gerrardii Root bark Garcigerrin B (5) Where Reference collected Africa et al. (1992) South Africa South Africa Sordat-Diserens et al. (1989) Sordat-Diserens et al. (1989) G. gerrardii Root bark 2-(1',l'-Dimethylprop-2' -enyl)-1,4,5-trihydroxy G. gerrardii xanthone (98) Root bark South Africa Sordat-Diserens et al. (1989) Macluxanthone (99) Stem bark Cameroon Waterman et al. (1980) Cameroon Waterman and Hussain (1982) G. ovalifolia 1,3,5-Trihydroxy-4,8-(3 ’,3’-dimethylallyl)xanth G. quadrifaria Stem bark one (100) Garceduxanthone (37) G. edulis Root bark Forbexanthone (101) G. edulis Root bark 83 Tanzania Magadula (2010) Tanzania Magadula (2010) Waterman and Pyranojacareubin (102) G. densivenia Stem bark Cameroon Crichton (1980) Ampofo and Nervosaxanthone (103) G. nervosa Nigeria Waterman (1986) Garciniaxanthone I Lannang et al. Root bark Cameroon (2008) (104) Lannang et al. Chefouxanthone (105) Root bark Cameroon (2008) Polyanxanthone A (38) Wood trunk Cameroon Louh et al. (2008) Polyanxanthone B (39) Wood trunk Cameroon Louh et al. (2008) Polyanxanthone C (40) Wood trunk Cameroon Louh et al. (2008) 1,3,6,7-Tetrahydroxyxa Wood trunk Cameroon Louh et al. (2008) nthone (106) 1,6-Dihydroxy-5-metho Wood trunk Cameroon Louh et al. (2008) xyxanthone (42) 1,3,5,6-Tetrahydroxyxa Wood trunk Cameroon Louh et al. (2008) nthone (107) 1,2-Dihydroxyxanthone Momo et al. G. lucida Stem bark Cameroon (2011) (108) 1-Hydroxy-3-methoxyx Momo et al. G. lucida Stem bark Cameroon anthone (109) (2011) Garcicosin (19) Other Compound Brevipsidone A (44) s Brevipsidone B (45) G. verrucosa Stem bark ssp orientalis G. brevipedicella Stem bark ta G. Stem bark brevipedicella Madagasc Rajaonarivelo et ar al. (2009) Cameroon Ngoupayo et al. (2008) Cameroon Ngoupayo et al. (2008) 84 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies Class Name Brevipsidone C (46) Brevipsidone D (47) β-Sitosterol (110) Plant species Part ta G. brevipedicella Stem bark ta G. brevipedicella Stem bark ta G. afzelii Stem bark G. polyantha Root bark Where Reference collected Cameroon Ngoupayo et al. (2008) Cameroon Ngoupayo et al. (2008) Waffo et al. (2006) Lannang et al. Cameroon (2008) Momo et al. Cameroon (2011) Cameroon G. lucida Stem bark β-Sitosterol-glucopyran G. lucida oside (111) Stem bark Cameroon Fotie et al. (2007) Stigmasterol (112) G. nervosa Dried leaf Nigeria G. lucida Stem bark Conrauanalactone (113) G. conrauana Stem bark, leaf, seed 3-(3’’,3’’-Dimethylallyl Stem bark, )-conrauanalactone G. conrauana leaf, seed (114) 5,7-Dihydroxychromon Stem bark, G. conrauana e (115) leaf, seed 3α-Hydroxy-5-(heptade c-8’-enyl)-tetrahydrofur G. mannii Stem bark an-2-one (116) Garcifuran A (117) Parveen et al. (2004) Momo et al. Cameroon (2011) Hussain and Cameroon Waterman (1982) Cameroon Hussain and Waterman (1982) Cameroon Hussain and Waterman (1982) Cameroon Hussain and Waterman (1982) Niwa et al. (1994a) Terashima et al. (1999b) Niwa et al. (1994a) Terashima et al. (1997) Terashima et al. (1997) Niwa et al. (1994b) Niwa et al. (1994b) G. kola Dried root Nigeria G. kola Dried stem Nigeria Garcifuran B (118) G. kola Dried root Nigeria Garcinal (25) G. kola Dried seed Nigeria Garcinoic acid (26) G. kola Dried seed Nigeria Garcipyran (119) G. kola Dried root Nigeria Dried root Nigeria Stem bark Cameroon Fotie et al. (2007) Stem bark Cameroon Fotie et al. (2007) 2,4-Dimethoxy-6-hydro G. kola xyacetophenone (120) Dihydrochelerythrine G. lucida (48) 6-Acetonyldihydrochel G. lucida erythrine (49) Chapter 4 Phytochemistry of African Garcinia Plants Class Where collected Cameroon DR Congo DR Congo DR Congo DR Congo DR Congo DR Congo DR Congo DR Congo DR Congo DR Congo DR Congo DR Congo Name Plant species Part Lucidamine A (50) G. lucida Stem bark Damnacanthal (20) G. huillensis Root bark Nordamacanthal (121) G. huillensis Root bark 2-Formyl-1-hydroxyant G. huillensis hraquinone (122) Root bark Lucidin (123) G. huillensis Root bark G. huillensis Root bark G. huillensis Root bark G. huillensis Root bark Rubiadin (127) G. huillensis Root bark Rubiadin 3-methyl ether (128) G. huillensis Root bark Tectoquinone (129) G. huillensis Root bark Rubiadin dimethyl ether (130) G. huillensis Root bark Pachybasin (131) G. huillensis Root bark δ-Tocotrienol (132) G. kola Seed Nigeria G. lucida Stem bark Cameroon G. lucida Stem bark Cameroon G. lucida Stem bark Cameroon G. lucida G. lucida Stem bark Stem bark Cameroon Cameroon Lucidin 1,3-dimethyl ether (124) Damnacanthol 1-methyl ether (125) Rubiadin 1-methyl ether (126) 30-Hydroxycycloarteno l (133) 31-Norcycloartenol (134) 24,25-Epoxy-31-norcyc loartenol (135) Sesamin (136) Trans-fagaramide (137) 85 Reference Fotie et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Dibwe et al. (2007) Terashima et al. (1997) Nyemba et al. (1990) Nyemba et al. (1990) Nyemba et al. (1990) Fotie et al. (2007) Fotie et al. (2007) 4.2 Benzophenones Plants of the genus Garcinia, produce a series of oxidized and isoprenylated benzophenones that are believed to originate from the mixed shikimate and acetate biosynthetic pathways (Beerhues and Liu, 2009). Many benzophenone compounds from the genus Garcinia contains the cyclohexatrione moiety, 86 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies which is generated by incorporation of several isoprenyl groups into C-2 and C-4 of a 1,3,5-trihydroxybenzophenone to form a bicyclo[3.3.1]nonane. This type of bridged polycyclic skeletons is widely distributed in the genus Garcinia and they are associated with a wide range of biological and pharmacological activities. Thus, the benzophenone derivatives can be regarded as useful candidates for drug development. Phytochemical reports from Garcinia plants of African origin revealed the isolation of many polyisoprenylated benzophenones. Currently, there are about nine benzophenone compounds reported from nine African Garcinia plants (Table 5). Hence, garcinol (51), a polyisoprenylated benzophenone derivative isolated from the stem bark of G. huillensis (Bakana et al., 1987), has been reported to possess antioxidative (Yamaguchi et al., 2000) and anti-HIV (Gustafson et al., 1992) activities. Recently, garcinol has been reported as a pleiotropic agent capable of modulating key regulatory cell signaling pathways as well as an anti-cancer agent (Padhye et al., 2009). In another study, three novel polyprenylated benzophenones, named semsinones A-C (53-55), have been isolated from a Tanzanian plant, Garcinia semseii (Magadula et al., 2008). Other benzophenones are xanthochymol (52), guttiferones A (36) and E (57), isoxanthochymol (13) and kolanone (58) being isolated from G. staudtii (Waterman & Hussain, 1982), G. livingstoneii, G. ovalifolia, G. polyantha (Gustafson et al., 1992) and G. kola (Iwu et al., 1990), respectively. 4.2 Flavonoids Flavonoids are polyphenols and water-soluble compounds that are known to be beneficial to human health (Iriti and Varoni, 2013). They are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine Chapter 4 Phytochemistry of African Garcinia Plants 87 is used to produce 4-coumaroyl-CoA. This can be combined with malonyl-CoA to yield the true backbone of flavonoids (Ververidis et al., 2007). Flavonoids are consumed by many animals including humans in their diets, due to their well known low toxicity compared to other active plants secondary metabolites like alkaloids. They have also been reported in some other studies to be biologically effective as "response modifiers", showing anti-allergic, antioxidant, anti-inflammatory activities (Cushnie and Lamb, 2005). In Garcinia plants, flavonoids and their derivatives are considered as the main components. More than 30 flavonoids have been isolated from Garcinia species found in Africa. These include flavones, flavanones, biflavanones, flavonols and flavonoid glycosides (Table 5). From the root bark of African mangosteen cultivated in Tanzania, two flavanones, namely volkensiflavone (67) and morelloflavone (68), were isolated (Mbwambo et al., 2006), while from G. kola, the most studied African Garcinia plant, about 25 flavonoids were reported by different researchers (Table 5). For instance, biflavanoids such as Garcinia biflavanone GB-1 (3), Garcinia biflavanone GB-2 (24), were reported to be dominant in the dried seeds of G. kola (Okunji and Iwu, 1991; Iwu and Igboko, 1982; Madubunyi, 1995; Kapadia et al., 1994). Several other flavonoids isolated from African Garcinia species have been reported in the literature (Table 5). 4.3 Triterpenoids Triterpenoids belong to a large and structurally diverse class of naturally occurring organic compounds which are distributed throughout the plant kingdom. They are commonly found in higher plants, lower animals (anthropods, coelenterates and molluscs), fungi, lichens and algae (Leistner, 2000). This class of compounds comprises natural products which are derived 88 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies from a common biosynthetic pathway based on mevalonate as parent, with a configuration of 30 carbons and several oxygens attached. Triterpenoids have been reported to have a wide spectrum of biological activities including cytotoxic, fungicidal, antiviral, analgesic, cardioprotective, spermicidal and anticancer properties (Lee, et al., 1988). From African Garcinia plants, only nine (9) triterpenoids have been reported (Table 5). These include friedelin (80), isolated from the stem bark of G. ovalifolia (Waterman et al., 1980), G. polyantha (Lannang et al., 2005) and G. edulis (Magadula, 2010). Other pentacyclic triterpenoids, oleanoic acid (81) and lupeol (82) were isolated from the stem barks of G. polyantha (Lannang et al., 2005), while, from the root bark of G. edulis, lupeol was isolated together with its acetate (84) (Magadula, 2010). In another study from G. semseii, a plant which is endemic to Tanzania, a monocyclic triterpene, achilleol A (83) was reported from its stem bark (Magadula et al., 2008). Other triterpenoids isolated from African Garcinia plants are indicated in Table 5. 4.4 Xanthones Xanthones are secondary metabolites whose basic structure is always flanked with a variety of oxygenated and prenylated groups, being reported to occur in some genera of higher plants including Garcinia. The diverse substitution patterns of xanthones provide a good basis for different biological activity and also for structure-activity relationship studies (Ee at al., 2005). Natural xanthones can be subdivided, based on the nature of substituents, into simple oxygenated xanthones, glycosylated xanthones, prenylated xanthones and their derivatives, xanthone dimers, xanthonolignoids and miscellaneous (Pinto et al., 2005). Currently, over 200 xanthones have been identified worldwide (Obolskiy et al., 2009; Peres and Nagem, 1997). Extensive phytochemical investigations Chapter 4 Phytochemistry of African Garcinia Plants 89 from the genus Garcinia gave a variety of prenylated xanthones, some of them exhibited a wide range of biological and pharmacological activities, including cytotoxic, antimicrobial, antifungal, antioxidant, antimalarial, anti-HIV-1, anti-obesity and anti-parasitic activities (Minami et al., 1994). Many of these xanthones are found in the pericarp of the true mangosteen fruit, G. mangostana, which is a highly investigated plant in the genus Garcinia (Obolskiy et al., 2009). African Garcinia plants were reported to possess a long list of xanthones (Table 5). About 35 different types of xanthones have been reported, most of them from Garcinia plants collected in Cameroon, Nigeria, South Africa and Tanzania (Table 5). A phytochemical report from an African mangosteen (G. livingstoneii) gave 11 xanthones (Mbwambo et al., 2006; Sordat-Diserens et al., 1992) while, from a South African plant, G. gerrardii, garcigerrin A (4) and B (5) were isolated (Sordat-Diserens et al., 1989). From Cameroon, Waffo and co-workers investigated the stem bark of G. afzelii, from which two xanthones, afzeliixanthone A (21) and B (22) were isolated (Waffo et al., 2006). From Nigeria, rheediaxanthone (91) and rheediaxanthone A (92) were isolated from the stem bark of G. staudtii (Waterman and Hussain, 1982). Table 5 provides the whole list of xanthones isolated from African Garcinia plant species. 4.5 Other Compounds Apart from the the 4 classes of compounds mentioned above, a range of other compounds have also isolated from Garcinia plants. These include brevipsidones (44-47) previously isolated from the stem bark of a Cameroonian plant, G. brevipedicellata (Ngoupayo et al., 2008), and conrauanalactones (113-114) isolated from the stem bark, leaves and seeds of G. conrauana (Hussain and Waterman, 1982). Furthermore, garcifurans (116-119) were 90 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies isolated from G. kola (Niwa et al., 1994; Terashima et al., 1999) while the commonly known phytosterols, stigmasterol (110) and β-sitosterol (112) were also reported from many other Garcinia species growing in Africa (Table 5). OH OH HO O O O HO O OH O OH 52 51 OH OH HO O HO O R O HO O O O 53 O 54 R H 55 OH O OH HO OH OH HO O 56 O O HO O O O O OH OH 57 58 Fig. 21. Structures of compounds isolated from African Garcinia plants. Chapter 4 Phytochemistry of African Garcinia Plants OH OH OH HO O OH OH O HO O+ HO OH O OH HO O R H R 59 R' OH O OH R' H OH OH 60 H OH 61 OH H O 63 62 OH OH HO HO O O OCH3 HO R OH 91 O O OH OH R 64 H 65 OCH3 66 glc O HO OH O O OH HO OH O O 69 OH OH O 70 67 H 68 OH OH HO R7 O R2 O R3 R1 OH HO OH OH O O O 73 H OH O OH 72 OH HO O R2 R3 R4 R5 OCH3 H OH OCH3 74 OCH3 H OH OCH3 75 OCH3 H H O R7 OCH3 H OH H H OCH3 OH OH HO O OH HO O OH O 77 OH OH HO O OH OH OH O HO O O OH OH OH OH OH 76 OH R6 OCH3 OH O HO OH R4 R5 R1 O 71 R6 OH HO OH O OH O 78 OH O 79 Fig. 21. Structures of compounds isolated from African Garcinia plants (Cont). 92 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies H H H H H H COOH H H O HO 80 HO H H 82 81 H HO H H H3COO H 83 84 H HO H OH H H H3COO H 85 H COOH H HO H 86 COOH H HO H 87 H O OR 88 89 R H CH3 Fig. 21. Structures of compounds isolated from African Garcinia plants (Cont). Chapter 4 Phytochemistry of African Garcinia Plants O OH OH O OH 93 O O O OH O OH O OH 90 O 91 OH O OH 92 OH O OH O O OH O O OH O O 94 93 OH OH OH O O OH OH O OH OH 98 97 O O OH O O O OH O O 96 OH OH 95 OH O OH HO OH O O HO O OH OH O OH OCH3 O OH OH OH O 101 OH 99 100 OH O O OH O OH O O O OH 102 O HO O OH 103 OH OH OCH3 OH O 104 Fig. 21. Structures of compounds isolated from African Garcinia plants (Cont). 94 Garcinia Plant Species of African Origin: Ethnobotanical, Pharmacological and Phytochemical Studies O OH O OH OH O HO O OH HO O OCH3 O OH HO OH OH OH 106 107 105 O O H OH OH H OCH3 OH H O 109 108 H HO O 110 OH R H H H H H C14H29 O H H H O 113 R H HO Glc 112 111 HO O OH O HO HO O 114 O (CH2)6CH=CH(CH2)7CH3 OH H3CO O 116 115 117 Fig. 21. Structures of compounds isolated from African Garcinia plants (Cont). Chapter 4 Phytochemistry of African Garcinia Plants O O OCH3 HO OH HO OCH3 HO H3CO HO OCH3 OH O 119 118 120 R1 O R1 O CHO CH2OH R2 O OCH3 20 121 OH 122 H R1 O CH3 R2 O R1 R1 R2 OH 123 OH OH 124 OCH3 H 125 OCH3 R2 OH OCH3 OH R2 O O R1 126 OCH3 127 OH 128 H 129 OH R2 OH OH OCH3 O CH3 OCH3 O H OCH3 OH O 130 131 HO O CH3 132 HO H HO H OH 133 134 O O HO O O H 135 O O O O N H O O 136 137 Fig. 21. Structures of compounds isolated from African Garcinia plants (Cont). 95 References 1. Adaramoye OA, Awogbindin I, Okusaga JO, (2009). Effect of Kolaviron, a Biflavonoid Complex from Garcinia kola Seeds, on Ethanol-Induced Oxidative Stress in Liver of Adult Wistar Rats, J. Med. Food 12:584-590. 2. Adaramoye OA, Adeyemi EO, (2006). Hypoglycaemic and hypolipidaemic effects of fractions from kolaviron, a biflavonoid complex from Garcinia kola in streptozotocin-induced diabetes mellitus rats. J. Pharm. and Pharmacol., 8:121-128. 3. Adegboye MF, Akinpelu DA, Okoh A, (2008). The Bioactive and Phytochemical Properties of Garcinia kola (Heckel) Seed extract on some Pathogens, Afr. J. Biotechnol. 7:3934-3938. 4. Adegoke GO, Kumar, MV, Sambaiah, K, Lokesh BR (1998). Inhibitory effect of Garcinia kola on lipid peroxidation in rat liver homogenate. Indian J. Exper. Biology, 36:907-910. 5. Adesina SK, Gbile ZO, Odukoya OA, Akinwusi DD, Illoh HC, Jayeola AA, (1995). Survey of Indigenous Useful Plants of West Africa with Special Emphasis on Medicinal Plants and Issues Associated with their Management, 2 nd Ed. The United Nations University Programme on Natural Resources in Africa, pp. 84-85. 6. Adu-Tutu M, Afful Y, Asante-Appiah K, Lieberman D, Hall JB, Elvin-Lewis M, (1979). Chewing stick Usage in Southern Ghana. Econ. Botany, 33:320-328. 7. Agada PO, Braide VB, (2009). Effect of dietary Garcinia kola seed on selected serum electrolytes and trace metals in male albino rats. Nigerian J. Physiol. Sci., 24:53-57. 8. Agyili J, Sacande M, Koffi E, Peprah T (2007). Improving the collection and germination of West African Garcinia kola Heckel seeds, New Forests, 34:269-279. 9. Akendengue B, Louis AM (1994). Medicinal Plants used by the Masango People in Gabon. J. Ethnopharmacol., 41:193-200. 10. Akerele JO, Obasuyi O, Ebomoyi MI, Oboh IE, Osamuyi H (2008). Antimicrobial activity of the ethanol extract and fractions of the seeds of Garcinia kola Heckel (Guttiferae), Afr. J. Biotech., 7:169-172. 11. Akintonwa A, Essie AR (1990). Protective Effects of Garcinia kola Seed extract against Paracetamol-induced Hepatotoxicity in Rats. J. Ethnopharmacol., 29:207-211. 98 References 12. Ambasta SP (1986). The Useful Plants of India, CSIR, New Delhi, p 231 13. Ampofo SA, Waterman PG (1986). Xanthones from three Garcinia species. Phytochem., 25:2351-2355. 14. Arnold HJ, Gulumian M (1984). Pharmacopoeia of Traditional Medicine in Venda. J. Ethnopharmacol., 12:35-74. 15. Bakana P, Claeys M, Totte J, Pietters LAC, Van Hoof L, Tamba V, Van den Berghe DA, Vlietinck AJ (1987). Structure and Chemotherapeutical Activity of a Polyisoprenylated Benzophenone from the stem bark of Garcinia huillensis. J. Ethnopharmacol., 21:75-84. 16. Balemba, OB, Bhattarai, Y, Stenkamp-Strahm, Lesakit, MSB, Mawe GM (2010). The traditional antidiarrheal remedy, Garcinia buchananii stem bark extract, inhibits propulsive motility and fast synaptic potentials in the guinea pig distal colon. Neurogastroenterology & Motility, 22:1332–1339. 17. Bamps P, Robson N, Verdcourt B (1978). Flora of Tropical East Africa: Guttiferae, Crown Agents for Oversea Governments and Administrations, pp. 14. 18. BBC News bulletin, 1999. 19. Beerhues L, Liu B (2009). Biosynthesis of Biphenyls and Benzophenones-Evolution of Benzoic acid-specific type III Polyketide Synthases in Plants. Phytochem., 70:1719-27. 20. Braide VB (1991). Antihepatotoxic biochemical effects of Kolaviron, a biflavonoid of Garcinia kola seeds. Phytother. Res., 5:35-37. 21. Braide VB (1989). Antispasmodic Extracts from seeds of Garcinia kola. Fitoterapia, 60:123-129. 22. Braide VB (1991). Inhibition of Drug Metabolism by Flavonoid Extract (kolaviron) of Garcinia kola seeds in the rat. Phytother. Res., 5:38-40. 23. Braide VB (1990). Pharmacological effects of Chronic Ingestion of Garcinia kola seeds in the rat. Phytother. Res., 4:39-41. 24. Burgess N, Doggart N, Lovett JC (2002). The Uluguru Mountains of Eastern Tanzania: The Effect of Forest loss on Biodiversity. Oryx, 36, 140-152. 25. Bruce-Chwatt LJ, Black RH, Canfield CJ, Clyde DF, Peters W, Wernsdorfeeer WH (1981). World Health Organization (WHO), Chemotherapy of Malaria, 2nd Edn. 26. Boakye PA, Stenkamp-Strahm C, Bhattarai Y, Heckman MD, Brierley SM, Pasilis SP, Balemba OB (2012). 5-HT(3) and 5-HT(4) receptors contribute to the References 99 anti-motility effects of Garcinia buchananii bark extract in the guinea-pig distal colon. Neurogastroenterol Motil. 24:27-40. 27. Boakye PA, Brierley SM, Pasilis SP, Balemba OB (2012). Garcinia buchananii bark extract is an effective anti-diarrheal remedy for lactose-induced diarrhea, J Ethnopharmacol. 142:539-547. 28. Bouquet A, (1969). Fet́icheurs et me´decines Traditionnelles du Congo (Brazzaville). O.R.S.T.O.M., Paris, p. 133. 29. Cepleanu F, Hamburger MO, Sordat B, Msonthi JD, Gupta MP, Saadou, M, Hostettmann K (1994). Screening of Tropical Medicinal Plants for Molluscicidal, Larvicidal, Fungicidal and Cytotoxic activities and Brine Shrimp toxicity. Intern. J. Pharmacog., 32:294-307. 30. Chapuis JC, Sordat B, Hostettmann K (1988). Screening for Cytotoxic Activity of Plants used in Traditional Medicine. J. Ethnopharmacol., 23:273-284. 31. Chantarasriwong O, Batova A, Chavasiri W, Theodorakis EA. (2010). Chemistry and Biology of the caged Garcinia xanthones. Chemistry.16(33):9944-62. 32. Cheek M (2008). IUCN Red List of Threatened Species, 2004. 33. Chiang YM, Kuo YH, Oota S, Fukuyama Y., (2003). J. Nat. Prod., 66:1070-1073. 34. Coates PM (2002). Keith Coates Palgrave Trees of southern Africa, Edn 3. Struik, Cape Town. 35. Cushnie TPT, Lamb AJ (2005). Antimicrobial activity of Flavonoids. Intern. J. Antimicr. Agents, 26:343–356. 36. Dalziel JM (1937). The Useful Plants of West Tropical Africa. Crown Agents for the Colonies, London. 37. Dufresne CJ, Farnsworth ER (2001). A review of the latest findings on Health Promoting properties in Tea. J. Nutr. Biochem., 12:404-421. 38. Ebana RUB, Madunagu BE, Ekpe ED, Otung IN (1991). Microbiological Exploitation of Caridac glycosides and Alkaloids from Garcinia kola, Borreria ocymoides, Kola nitida and Citrus aurantifolia. J. Appl. Bacteriol., 71:398-401. 39. Ee GCL, Lim Rahmat CKA (2005). Nat. Prod. Sci., 11:220-224. 40. Elujoba AA (1995). Female Infertility in the hands of Traditional Birth Attendants in South-western Nigeria. Fitoterapia, 66:239-248. 41. Fadulu SO (1975). The Antibacterial Properties of the Buffer Extracts of Chewing Sticks used in Nigeria. Planta Med., 27:122. 100 References 42. Farombi EO, Akanni OO, Emerole O (2002). Antioxidant and Scavenging Activities of Flavonoid Extract (kolaviron) of Garcinia kola seeds. Pharmaceutical Biol., 40:107-116. 43. Farombi EO, Mller P, Dragsted LO (2004). Ex-vivo and in vitro protective effects of kolaviron against oxygen-derived radical. Cell Biol & Toxicol., 20:71-82. 44. Farombi EO, Shrotriya S., Surh YJ (2009). Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-κB and AP-1. Life Sciences, 84:149-155. 45. Fita DD, Suresh A, Shigetoshi K, Yasuhiro T. (2012). Damnacanthal from the Congolese Medicinal Plant Garcinia huillensis has a Potent Preferential Cytotoxicity against Human Pancreatic Cancer PANC‐1 Cells, Phytother. Res., 26: 1920-1926. 46. Fotie J, Bohle DS, Olivier M, Gomez MA, Nzimiro S (2007). Trypanocidal and Antileishmanial Dihydrochelerythrine Derivatives from Garcinia lucida. J. Nat. Prod. 70:1650-1653. 47. Freiburghaus F, Ogwal EN, Nkunya MHH, Kaminsky R, Brun R (1996). In vitro Antitrypanosomal activity of African Plants used in Traditonal Medicine in Uganda to treat Sleeping Sickness. Trop. Med. & Intern. Health, 1:765-771. 48. Gartlan JS, Mckey DB, Waterman PG, Mbi CN, Struhsaker TT (1980). A comparative Study of the Phytochemistry of two African rain forests. Biochemical Systematic and Ecol., 8:401-422. 49. Gill LS, Akinwumi C (1986). Nigerian Folk Medicine: Practices and Beliefs of the Ondo people. J. Ethnopharmacol., 18:259-266 50. Glen HF (2004). SAPPI What's in a name? Jacana, Johannesburg. 51. Gustafson KR, Blunt JW, Munro MHG, Fuller RW, McKee TC, Cardellina II JH, McMahon JB, Cragg GM, Boyd MR (1992). The Guttiferones, HIV Inhibitory Benzophenones from Symphonia globulifera, Garcinia livingstonei, Garcinia ovalifolia and Clusia rosea. Tetrahedron, 48:10093-10102. 52. Han QB, Lee SF, Qiao CF, He ZD, Song JZ, Sun HD, Xu HX (2005). Complete NMR Assignments of the Antibacterial Biflavonoid GB-1 from Garcinia kola. Chem. Pharm. Bull., 53:1034-1036. 53. Herbin GA, Jackson B, Locksley HD, Scheinmann F, Wolstenholme WA (1970). The Biflavonoids of Garcinia volkenszi (Guttiferae). Phytochem., 9:221-226. References 101 54. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C (1998). Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: A randomized controlled trial, JAMA, 11; 280(18):1596-600. 55. Hussain RA, Waterman PG (1982). Lactones, flavonoids and benzophenones from Garcinia conrauana and Garcinia mannii. Phytochem., 21:1393-1396. 56. Hussain RA, Owegby AG, Parimoo P, Waterman PG (1982). Kolanone, a Novel Polyisoprenylated Benzophenone with Antimicrobal Properties from the fruit of Garcina kola. Planta Med., 44:78-81. 57. Ilyas M, Kamil M, Parveen M, Khan MS (1994). Isoflavones from Garcinia nervosa. Phytochem., 36:807-809. 58. Iriti M, Varoni EM, (2013). Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies, Nutrients, 5(7):2564-2576. 59. Ito C, Itoigawa M, Mishina Y, Tomiyasu H, Litaudon M, Cosson JP, Mukainaka T, Tokuda H, Nishino H, Furukawa H (2001). Cancer chemopreventive agents. New depsidones from Garcinia plants. J. Nat. Prod., 64:147-150. 60. Iwu MM, Anyanwu BN (1982). Phytotherapeutic Profile of Nigerian Herbs. 1. Anti-inflammatory and Anti-arthritic agents. J. Ethnopharmacol., 6:263-274. 61. Iwu MM, Igboko OA, Tempesta MS (1990). Biflavonoid Constituents of Garcinia kola roots. Fitoterapia, 61:178-181. 62. Iwu MM (1985). Antihepatoxic Constituents of G. kola seeds. Experientia, 41:699-700. 63. Iwu M, Igboko OA (1982). Flavonoids of Garcinia kola seeds. J. Nat. Prod., 45:650-651. 64. Iwu M, Igboko OA, Onwuchekwa UA, Okunji CO (1987). Evaluation of the Antihepatotoxic activity of the Biflavonoids of Garcinia kola seeds. J. Ethnopharmacol., 21:127-138. 65. Iwu MM, Igboko OA, Elekwa OK, Tempesta MS (1990). Prevention of Thioacetamide-induced Hepatotoxicity by Biflavanones of Garcinia kola. Phytother. Res., 4:157-159. 66. Iwu MM, Igboko OA, Onwuchekwa U, Okunji CO (1987). Evaluation of the anti-hepatotoxicity of the biflavonoids of Garcinia kola seeds. J. Ethnopharmacol., 21:127-142. 67. Iwu, M. 1993. Handbook of African Medicinal Plants. CRC Press, Boca Raton, FL. 102 References 68. Jackson B, Locksley HD, Scheinmann F, Wolstenholme WA (1971). Extractives from Guttiferae. Part XXII. The Isolation and Structure of Four Novel Biflavanones from the Heartwoods of Garcinia buchananii Baker and G. eugeniifolia Wall. J. Chem. Soc C 1971:3791-3804. 69. Johns T, Mhoro EB, Sanaya P (1996). Food Plants and Masticants of the Batemi of Ngorongoro district, Tanzania. Econ. Botany, 50:115-121. 70. Kabangu K, Galeffi C, Aonzo E, Nicoletti M, Messana I (1987). A new Biflavanone from the Bark of Garcinia kola-1. Planta Med., 53:275-277. 71. Kaikabo AA., Samuel, B.B., Eloff, JN (2009). Isolation and activity of two antibacterial biflavonoids from leaf extracts of Garcinia livingstonei (Clusiaceae). Nat. Prod. Communic’, 4: 1363-1366. 72. Kaikabo AA, Eloff, JN (2011). Antibacterial activity of two biflavonoids from Garcinia livingstonei leaves against Mycobacterium smegmatis. J Ethnopharmacol. 138:253-255. 73. Kambu K, Tona L, Kaba S, Cimanga K, Mukala N (1990). Antispasmodic activity of Extracts Proceeding of Plant Antidiarrheic Traditional Preparations used in Kinshasa, Zaire. Ann. Pharm. Fr., 48:200-208. 74. Kapadia GJ, Oguntimein B, Shukla YN (1994). High-speed Counter-current Chromatographic Separation of Biflavonoids from Garcinia kola seeds. J. Chromat., 673:142-146. 75. Kpakote KG, Aakpagana K, de Souza C, Nenonene AY, Djagba TD, Bouchet P (1998). Antimicrobial Activities of some Togolese species of Chewing Sticks. Ann. Pharm. Fr., 56:184-186. 76. Laine C, Baniakina J, Vaquette J, Chaumont JP, Simeray J (1985). Antifungal activity of Barks from Congolese Phanerogames. Plant & Med. Phytother., 19:75-83. 77. Lannang AM, Komguem J, Ngninzeko FN, Tangmouo JG, Lontsi D, Ajaz A, Choudhary MI, Ranjit R, Devkota KP, Sondengam BL (2005). Bangangxanthone A and B, two xanthones from the stem bark of Garcinia polyantha Oliv. Phytochem., 66:351-2355. 78. Lannang AM, Louh GN, Lontsi D, Specht S, Sarite SR, Flörke U, Hussain H, Hoerauf A, Krohn K, (2008). Antimalarial compounds from the root bark of Garcinia polyantha Olv. J. Antibiotics, 61:518-23. 79. Lee KH, Lin YM, Wu TS, Zhang DC, Yamagishi T, Hayashni T, Hall IH, Chang JJ, Wu RY, Yang TH (1988). The cytotoxic principles of Prunella vulgaris, References 103 Psychotria serpens, and Hyptis capitata: Ursolic acid and related derivatives. Planta Med., 54:308-311. 80. Leistner OA, (2000). Seed plants of southern Africa: Families and genera, Strelitzia 10, National botanical institute, Pretoria, p. 610. 81. Louh GN, Lannang AM, Mbazoa CD, Tangmouo JG, Komguem J, Castilho P, Ngninzeko FN, Qamar N, Lontsi D, Choudhary MI, Sondengam BL (2008). Polyanxanthone A, B and C, three xanthones from the wood trunk of Garcinia polyantha Oliv. Phytochem., 69:1013-1017. 82. Lovett, J. & Clarke, G.P. 1998. Garcinia acutifolia. 2006 IUCN Red List of Threatened Species. Downloaded on 20 July 2007. 83. Lovett, J. 1996. Completed data collection forms for restricted range trees of Tanzania. 84. Lutete T, Kambu K, Ntondele D, Cimanga K, Luki N (1994). Antimicrobial Activity of Tannins. Fitoterapia, 65:276-278. 85. Mabberley DJ (2002). The plant-book. Cambridge University Press, Cambridge. 86. Mabberly DJ (1993). The Plant-Book: A Portable Dictionary of the Higher Plants; Cambridge University Press: New York, p 236. 87. Madubunyi II (1995). Antimicrobial Activities of the Constituents of Garcinia kola seeds. Intern. J. Pharmacog., 33:232-237. 88. Magadula JJ, Kapingu MC, Bezabih M, Abegaz BM, (2008). Polyisoprenylated Benzophenones from Garcinia semseii (Clusiaceae). Phytochem. Lett., 1:215-218. 89. Magadula JJ (2010). A Bioactive Isoprenylated Xanthone and other Constituents of Garcinia edulis. Fitoterapia, 81:420-423. 90. Magadula JJ, Tewtrakul S (2010). Anti-HIV-1 Protease Activities of Crude Extracts of some Garcinia species Growing in Tanzania. Afr. J. Biotech., 9:1848-1852. 91. Magadula JJ, Suleiman HO (2010). Cytotoxic and anti-HIV activities of some Tanzanian Garcinia species. Tz. J. Health Res., 12:1-7. 92. Magadula JJ (2012). Bioactive benzophenones from stem bark and fruit hulls of Garcinia semseii Verdc, Int. J. Res. Phytochem & Pharmacol., 2:261-265. 93. Mathias ME (1982). Some Medicinal Plants of the Hehe (Southern Highlands Province, Tanzania).Taxon, 31:488-494. 104 References 94. Mbafor JT, Fomum ZT, Promsattha R, Sanson DR, Tempesta MS (1989). Isolation and Characterization of taxifolin 6-C-glucoside from Garcinia epunctata. J. Nat. Prod., 52:417-419. 95. Mbwambo ZH, Kapingu MC, Moshi MJ, Machumi F, Apers S, Cos P, Ferreira D, Marais JPJ, Berghe DV, Maes L, Vlietinck A, Pieters L, (2006). Antiparasitic Activity of Some Xanthones and Biflavonoids from the Root Bark of Garcinia livingstonei. J. Nat. Prod., 69:369-372. 96. Mbwambo ZH, Magadula JJ, Gatto J., Richomme P. (2011). Phytochemical and Pharmacology effects of Phenolic compounds from Garcinia volkensii Engl., Spatula DD, 2:1-7. 97. Minami H, Kinoshita M, Fukuyama Y, Kodama M, Yoshizawa T, Sugiura M, Nakagawa K, Tago H (1994). Antioxidant xanthones from Garcinia subelliptica. Phytochem., 36:501-506. 98. Momo IJ, Kuete V, Dufat H, Michel S, Wandji J (2011). Antimicrobial Activity of the Methanolic Extract and Compounds from the Stem bark of Garcinia lucida Vesque (Clusiaceae), Inter. J. Pharm. Pharmaceutical Sc., 3:215-217. 99. Ngoupayo J, Tabopda TK, Ali MS, Tsamo E (2008). α-Glucosidase Inhibitors from Garcinia brevipedicellata (Clusiaceae). Chem. Pharm. Bull., 56:1466-1469. 100. Niwa M, Terashima K, Ito J, Aqil M (1994a). Two Novel Arylbenzofurans, Garcifuran-A and Garcifuran-B from Garcinia kola. Heterocycles, 38:1071-1076. 101. Niwa M, Terashima K, Ito J, Aqil M (1994b). Garcipyran, a Novel 6-aryl-1,2-benzopyran Derivative from Garcinia kola. Heterocycles, 38:1927-1932. 102. Nyemba AM, Mpondo TN, Connolly JD, Rycroft DS (1990). Cycloartane derivatives from Garcinia lucida. Phytochem., 29:994-997. 103. Novy JW (1997). Medicinal Plants of the Eastern Region of Madagascar. J. Ethnopharmacol., 55:119-126. 104. Obolskiy D, Pischel I, Siriwatanametanon N, Heinrich M (2009). Garcinia mangostana L.: A Phytochemical and Pharmacological Review. Phytother. Res., 23:1047-1065. 105. Okoko T, (2009). In vitro antioxidant and free radical scavenging activities of Garcinia kola seeds. Food & Chem. Toxicol., 47:2620-2623 106. Okunji CO, Iwu MM (1988). Control of Schistosomiasis using Nigerian Medicinal Plants as Molluscicides. Intern. J. Crude Drug Res., 26:246-252. References 105 107. Okunji CO, Iwu MM (1991). Molluscicidal Activity of Garcinia kola Biflavanones. Fitoterapia, 62:74-76. 108. Orie NN, Ekon EU, (1993). The Bronchodilatory effect of Garcinia kola. E. Afr. Med. J., 70:143–145. 109. Oruambo IF (1989). Alteration of glucose-6-phosphatase activity and regenerative, and total DNA concentrations in regenerating and normal rat liver of aqueous extracts of two Nigerian plants. J. Environ. Pathol. Toxicol. Oncol., 9:191-199. 110. Oze G, Okoro I, Obi A, Nwoha P, (2010). Hepatoprotective role of Garcinia kolanut (Heckel) extract on methamphetamine: Induced neurotoxicity in mice. Afr. J. Biochem. Res., 4:81-87. 111. Padhye S, Ahmad A, Oswal N, Sarkar FH (2009). Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs, J. Hematology & Oncol., 2:38. 112. Palgrave CM (2002). Keith Coates Palgrave Trees of southern Africa, edn 3. Struik, Cape Town. 113. Parveen M, Ilyas M, Mushfiq M, Busudan OA, Muhaisen HMH (2004). A New Biflavonoid from Leaves of Garcinia nervosa. Nat. Prod. Res., 18:269-275. 114. Perry LM, Metzger J. (Eds.), (1980). Medicinal Plants of East and South-East Asia. MIT Press, London, p. 175. 115. Peres V, Nagem TJ (1997). Trioxygenated Naturally occurring Xanthones. Phytochem., 44:191-214. 116. Pinto MM, Sousa ME, Nascimento MS (2005). Xanthone derivatives: New Insights in Biological activities. Curr. Med. Chem., 12:2517-2538 117. Philipson JD, Wright CW (1990). Antiprotozoal Agents from Plant sources. Planta Med., 57:53-59. 118. Polhill RM (1968). Tanzania vegetation. In Inga and Olov Herdberg (eds.). Conservation of vegetation in Africa South of Sahara. Almqvist & Wiksells Boktykeri AB, Uppsala, Sweden, pp. 1666-70. 119. Rajaonarivelo M, Rakotonandrasana O, Raharinjato F, Martin MT, Dumontet V, Rasoanaivo P, Gueritte F (2009). New Cytotoxic Compounds from Madagascar Plants. Proceedings of Biomedical symposium, Antanarivo, Madagascar, p. 65. 120. Rates SMK (2001). Plants as source of drugs, Toxicon, 39, pp. 603–613. 121. Rogers ZS, Sweeney PW (2007). Two Distinctive New Species of Malagasy Garcinia (Clusiaceae). Systematic Botany, 32:772-779. 106 References 122. Samuelsson G, Farah MH, Claeson P, Hagos M, Thulin M, Hedberg O, Warfa AM, Hassan AO, Elmi AH, Abdurahman AD, Elmi AS, Abdi YA, Alin MH (1992). Inventory of Plants used in Traditional Medicine in Somalia. II. Plants of the Families Combretaceae to Labiatae. J. Ethnopharmacol., 37:47-70. 123. Sandberg F, Cronlund A (1977). What can we still learn from Traditional Folklore Medicine? Examples from the results of a Biological Screening of Medicinal Plants from Equatorial Africa. Proceedings of the Third Asian Symposium Medicinal Plants & Spices, Colombo, Sri Lanka, February 6-12, 3:178-197. 124. Stark TD, Matsutomo T, Losch S, Boakye PA, Balemba OB, Pasilis SP, Hofmann T (2012). Isolation and Structure Elucidation of Highly Antioxidative 3,8″-Linked Biflavanones and Flavanone-C-glycosides from Garcinia buchananii Bark, J. Agric. Food Chem., 60:2053-2062. 125. Sordat-Diserens I, Rogers C, Sordat B, Hostettmann K (1992). Prenylated Xanthones from Garcinia livingstonei. Phytochem., 31:313-316. 126. Sordat-Diserens I, Marston A, Hamburger M, Rogers C, Hostettmann K (1989). Novel Prenylated Xanthones from Garcinia gerrardii HARVEY. Helv. Chim. Acta, 72:1001-1007. 127. Stark TD, Matsutomo T, Lösch S, Boakye PA, Balemba OB, Pasilis SP, Hofmann T. (2012). Isolation and structure elucidation of highly antioxidative 3,8″-linked biflavanones and flavanone-C-glycosides from Garcinia buchananii Bark. J Agric Food Chem., 60:2053-2062. 128. Stuart SN, Adams RJ, Jenkins MD (1990). Biodiversity in sub-Saharan Africa and its Islands. Conservation, Management and Sustainable Use. A contribution to the Biodiversity Conservation Strategy Programme. Occasional papers of the IUCN Species Survival Commission No. 6. IUCN, Gland, Switzerland. 129. Temu RPC, Andrew, SM (2008). Endemism of plants in the Uluguru Mountains, Morogoro, Tanzania. Forest Ecology and Management, 255:2858–2869. 130. Terashima K, Kondo Y, Aqil M, Wazin M, Niwa, M (1999a). A study of Biflavanones from the Stems of Garcinia kola (Guttiferae). Heterocycles, 50:283-290. 131. Terashima K, Shimamura T, Tanabayashi M, Aqil M, Akinniyi JA, Niwa M (1997). Constituents of the Seeds of Garcinia kola: two new Antioxidants, Garcinoic acid and Garcinal. Heterocycles, 45:559-1566. 132. Terashima K, Kondo Y, Aqil M, Niwa M (1999b). A new Xanthone from the stems of Garcinia kola. Nat. Prod. Lett., 14:91-97. References 107 133. Terashima K, Kondo Y, Aqil M, Niwa M (1995). Garccinianin, a novel Biflavonoid from the Roots of Garcinia kola. Heterocycles, 41:2245-2250. 134. Terashima K, Takaya Y, Niwa M (2002). Powerful Antioxidative Agents based on Garcinoic Acid from Garcinia Kola. Bioorganic and Medicinal Chemistry, 10:1619-1625. 135. Tona L, Ngimbi NP, Tsakala M, Mesia K, Cimanga K, Aspers S, de Bruyne T, Pieters L, Totte J, Vlietinck AJ (1999). Antimalarial Activity of 20 Crude Extracts from nine African Medicinal Plants used in Kinshasa, Congo. J. Ethnopharmacol., 68:193-203. 136. Tor-Anyiin TA, Shaato R, Oluma HOA (2005). Ethnobotanical Survey of Antimalarial Medicinal Plants amongst the Tiv people of Nigeria. J. Herbs, Spices Med. Plants, 10:61-74. 137. UICN, OMS, WWF, 1993. Directrices Sobre Conservacion de Plantas Medicinales Organizasion Mundial de la Salud (OMS). Union Internacional para la Conservacion de la Naturaleza (UICN) and World Wildlife Fund (WWF). Gland, Switzerland. 138. Vasileva B (1969) Plantes Medicinales de Guinee. Conakry, Republique de Guinee. 139. Ververidis FF, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (2007). Biotechnology of Flavonoids and other Phenylpropanoid-derived Natural Products. Part I: Chemical Diversity, Impacts on Plant Biology and Human Health. Biotech. J., 2:1214. 140. Waffo AFK, Mulholland D, Wansi JD, Mbaze LM, Powo R, Mpondo TN, Fomum ZT, König W, Nkengfack AE (2006). Afzeliixanthones A and B, Two New Prenylated Xanthones from Garcinia afzelii ENGL. (Guttiferae). Chem. Pharm. Bull., 54:448-451. 141. Waterman PG, Crichton EG (1980). Xanthones, Benzophenones and Triterpenes from the stem bark of Garcinia ovalifolia. Planta Med., 40:351-355. 142. Waterman PG, Crichton EG (1980). Xanthones and Biflavonoids from Garcinia densivenia Stem bark. Phytochem., 19:2723-2726. 143. Waterman PG, Hussain RA (1982). Major Xanthones from Garcinia quadrifaria and Garcinia staudtii stem barks. Phytochem., 21:2099-2101. 144. Watt JM, Breyer-brandwijk MG (1962). The Medicinal and Poisonous Plants of Southern and Eastern Africa. 2nd Ed, E. + S. livingstone, Ltd., London. 145. WHO (2007). National Cancer Control Programs: Policies and Management Guidelines, Geneva. 108 References 146. Yamaguchi F, Ariga T; Yoshimura Y; Nakazawa H (2000). Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J. Agric. Food Chem., 48:180-185. 147. Yu GD (1982). Medicinal Plants used for Abortion and Childbirth in Eastern-Africa. Chung Yao T'ung Pao, 7: 6-7. Appendix List of African Garcinia Species-Countrywise S/N Garcinia species Author Country where found 1 G. acutifolia N. Robson 2 G. afzelii Engl. Tanzania, Mozambique Ghana, Guinea, Togo, Cameroon, Nigeria 3 G. ambrensis 4 G. anjouanensis 5 G. aphanophlebia 6 G. arenicola 7 G. asterandra 8 G. bifasculata G. brevipedicellata N. Robson Tanzania (Bak. f.) Hutch. & Dalz Cameroon, Nigeria 10 G. buchananii Bak. 11 G. buchneri 12 G. calcicola 13 G. capuronii Engl. (Jumelle & H. Perrier) P. Sweeney & Z. S. Rogers Z. S. Rogers & P. Sweeney 14 G. cerasifer 15 G. chapelieri 16 G. chromocarpa (H. Perrier) P. F. Stevens (Planchon & Triana) H. Perrier Engl. 17 G. commersonii (Planchon & Triana) Vesque Madagascar 18 G. conrauana Engl. Cameroon 19 G. crassiflora Madagascar 20 G. dalleizettei 21 G. dauphinensis Jumelle & H. Perrier (H. Perrier) P. Sweeney & Z. S. Rogers P. Sweeney & Z. S. Rogers 22 G. decipiens (Baillon) Vesque Madagascar 23 G. disepala Vesque Madagascar 24 G. densivenia Engl. Cameroon 25 G. edulis * Exell Tanzania 26 G. epunctata Stapf Guinea, Ghana, Cameroon 27 G. ferrea * Pierre Tanzania 9 (H. Perrier) P. Sweeney & Z. S. Rogers (H. Perrier) P. Sweeney & Z. S. Rogers Baker (Jumelle & H. Perrier) P. Sweeney & Z. S. Rogers Jumelle & H. Perrier Madagascar Madagascar Madagascar Madagascar Madagascar Tanzania, Uganda, Kenya, Zimbabwe, Mozambique, Ethiopia Zambia Madagascar Madagascar Madagascar Madagascar Cameroon Madagascar Madagascar 110 Appendix List of African Garcinia Species-Countrywise 28 G. gerradii Harvey 29 G. huillensis Welw. ex Oliv. 30 G. indica* DC. 31 G. kingaensis Engl. 32 G. kola Heckel 33 G. livingstonei T. Anderson 34 G. lucida Vesque South Africa DR Congo, Mozambique, Tanzania, Zambia, Zimbabwe, Cameroon, Malawi, Ethiopia Tanzania (Zanzibar) Tanzania, Zambia, Zimbabwe, Mozambique Nigeria, Ghana, Cameroon, Ivory Coast, Guinea, DR Congo, South Africa, Tanzania, Kenya, Uganda, Somalia, Zambia, Zimbabwe, Mozambique, DR Congo, Madagascar, Ethiopia Cameroon 35 G. lowryi G. madagascariensis Z. S. Rogers & P. Sweeney Madagascar (Planchon & Triana) Pierre Madagascar 36 37 G. mangorensis 38 G. mangostana* (R. Viguier & Humbert) P. Sweeney & Z. S. Rogers L. 39 G. megistophylla P. Sweeney & Z. S. Rogers Madagascar 40 G. melleri Madagascar 41 G. multifida 42 G. mannii Baker (H. Perrier) P. Sweeney & Z. S. Rogers Oliv. 43 G. nervosa Miq., P. Sweeney Nigeria 44 G. orthoclada Baker Madagascar 45 G. ovalifolia Oliv. Cameroon, CAR, Togo 46 G. pachyclada Tanzania, Zambia 47 G. parvula 48 G. pauciflora N. Robison (H. Perrier) P. Sweeney & Z. S. Rogers Baker 49 G. pervillei (Planchon & Triana) Vesque Madagascar 50 G. polyantha Oliv. Cameroon, Togo, 51 G. polyphlebia Baker Madagascar 52 G. punctata Oliv. Gabon, Zambia 53 G. quadrifaria (Oliv.) Baill. ex Pierre Cameroon 54 G. semseii Verdc Tanzania 55 G. smeathmannii (Planch&Triana) Oliv. Cameroon, Tanzania 56 G. staudtii Nigeria, Cameroon, 57 G. thouvenotii Engl. (H. Perrier) P. Sweeney & Z. S. Rogers Madagascar Tanzania, Madagascar Madagascar Cameroon, Madagascar Madagascar Madagascar Appendix List of African Garcinia Species-Countrywise (H. Perrier) P. Sweeney & Z. S. Rogers P. Sweeney & Z. S. Rogers (H. Perrier) P. Sweeney & Z. S. Rogers 58 G. tsaratananensis 59 G. tsimatimia 60 G. urschii 61 G. verrucosa ssp orientalis H. Perrier Madagascar 62 G. volkensii Engl. Kenya, Malawi, Mozambique, Tanzania, Zambia, Zimbabwe 63 G. xanthochymus * Roxb. T. Anders Tanzania *Exotic species. Madagascar Madagascar Madagascar 111 Joseph Jangu Magadula was born in Magu district, Mwanza region, Tanzania. He received his BSc degree in Physics and Chemistry in 1997 at the University of Dar es Salaam, Tanzania. He then enrolled for an MSc degree in Chemistry at the same University, graduating in 2000. In 2003 he joined the University of KwaZulu-Natal, South Africa, receiving his PhD in PhytoChemistry in May 2006. He is now holding a position of Senior Research Fellow and serving as head of department of Natural Products Development and Formulations, Chairperson of NAPRECA (Tanzania) and Editor-in Chief of the ITM News Bulletin. Zakaria Heriel Mbwambo was born in Mamba-Ivuga, Same district, Kilimanjaro region, Tanzania. He received his MSc in Pharmacy at the Kharkov State Pharmaceutical Institute, Ukraine in 1984. He was then enrolled as a PhD candidate in 1991 at the University of Illinois at Chicago in the USA specializing in the Chemistry of Natural Products where he graduated in 1996. He was holding a position of Associate Research Professor until his death from brain tumor in July 2014. ISBN 194192610-X ISBN: 978-1-941926-10-9 Open Science 9 781941 926109 > Price: US $79