Journal of Ethnopharmacology 124 (2009) 339–349 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm Review The genus Bridelia: A phytochemical and ethnopharmacological review T.A. Ngueyem a,c , G. Brusotti a,c , G. Caccialanza a,c , P. Vita Finzi b,c,∗ a Department of Pharmaceutical Chemistry, University of Pavia, Pavia, Italy Department of Organic Chemistry, University of Pavia, Pavia, Italy c Center for Studies and Researches in Ethnobiopharmacy, (C.I.St.R.E.), University of Pavia, Pavia, Italy b a r t i c l e i n f o Article history: Received 23 July 2008 Received in revised form 17 May 2009 Accepted 18 May 2009 Available online 27 May 2009 Keywords: Bridelia Drug discovery screening Indigenous medicine Pain treatment a b s t r a c t Approximately 60 species of Bridelia, (Phyllanthaceae) are found throughout tropical and subtropical regions of the world, mainly in Africa and Asia. Several Bridelia species are used in popular medicines as antiamebic, antianemic, antibacterial, anticonvulsant, anti-diabetic, antidiarrhoeal, antihelmintic, anti-inflammatory, antimalarial, antinociceptive, antiviral, hypoglycemic and for abdominal pain, cardiovascular, gynecological and sexual diseases. The present paper reviews the traditional usage, the biological activities and the correlated chemical compounds of Bridelia species with emphasis on the validation of the ethnopharmacological uses. The findings in some Bridelia species of, for example, gallocatechin(4′ -O-7)-epigallocatechin (1), quercetin (2), myricetin glycosides (5–6), bridelone (11), bridelonine (12), isoflavone may justify the uses of these species against pains in African and Asian traditional medicines. © 2009 Elsevier Ireland Ltd. All rights reserved. Contents 1. 2. 3. 4. 5. 6. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Botany . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Metabolites occurring in Bridelia species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Medicinal uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Bridelia ferruginea Benth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Bridelia atroviridis Muell. Arg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Bridelia balansae Tucht. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4. Bridelia cathartica Bertol. f. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5. Bridelia crenulata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6. Bridelia glauca Bl. f. balansae Tucht. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.7. Bridelia grandis (Pierre ex Hutch) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.8. Bridelia micrantha (Hochst) Baill. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.9. Bridelia moonii Thw. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.10. Bridelia monoica (L.) Merr. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.11. Bridelia ndellensis Beille.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.12. Bridelia ovata Decne. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.13. Bridelia retusa (L.) Sprengel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.14. Bridelia scleroneura Mull-Arg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.15. Bridelia scleroneuroides Pax. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.16. Bridelia siamensis Craib. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.17. Bridelia stipularis Blume. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.18. Bridelia tomentosa Bl. (syn. Bridelia monoica Merr.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Critical assessment of ethnomedicinal properties, pharmacological activities and chemical compounds found in Bridelia spp. . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ∗ Corresponding author at: Department of Organic Chemistry, University of Pavia, Pavia, Italy. Tel.: +39 0382 987322; fax: +39 0382 987323. E-mail address: vitafinz@unipv.it (P.V. Finzi). 0378-8741/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2009.05.019 340 340 340 342 342 345 345 346 346 346 346 346 347 347 347 347 347 347 347 347 348 348 348 348 348 340 T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 1. Introduction Table 1 Bridelia spp. synonyms and botanical references to authorities. During our research on medicinal plants used in African forests by pigmies Baka, we focused our interest in the genus Bridelia. An ethnobotanical survey was conducted between February 2006 and July 2007 in South Cameroon forest (district of Djoum) to collect information about the use of plants for medicinal purposes. Studying Bridelia grandis stem bark (Ngueyem et al., 2008), which is used as a remedy for oral cavity affection, such as dental caries (Brisson, 1999), we noticed that several Bridelia species are traditionally used, throughout Africa and Asia, to reduce pain. Although these plants have been reported in the ethnobotanical literature or have been investigated phytochemically there are only a few detailed reports on their biological activities, toxicity and phytochemical contents which support the indigenous knowledge. This review will cover the last 35 years literature data on the pharmacological activities and the chemical compounds isolated from genus Bridelia together with an overview on traditional and local uses. Databases used to search for the literature were: Scifinder scholar, PubMed, Tropicos (for plant taxonomy) and Aluka. With the exception of the most studied species, Bridelia ferruginea, Bridelia species are reported in alphabetical order. Botanical data, pharmacological and ethnomedicinal properties and identified secondary metabolites are depicted in Tables 1 and 2, respectively. Bold Arabic numeral in the text refers to chemical structures reported in Fig. 1. Bridelia species Synonyms Bridelia abyssinica Pax. Bridelia micrantha Hochst. Baill. Bridelia mildbraedii Gehrm. Bridelia zanzibariensis Vatke & Pax. Candelabria micrantha Hochst. Baill. Bridelia neogoetzea Gehrm. Neogoetza brideliifolia Pax. Bridelia niedenzui var. Pilosa Gehrm. 2. Botany The genus Bridelia Willd. (Tribe Bridelieae, Phyllanthaceae, Order Malpighiales) (Kathriarachchi et al., 2005) includes approximately 60–70 species, from Africa to Asia. The genus is also known as: Candelabria Hochst, Gentilia A.Chev. & Beille, Pentameria Klotzsch ex Baill, Tzellemtinia Chiov. About 50 species are distributed in Tropical Africa, Madagascar, Yemen and in Asia ranging from India and South China throughout Indochina, Malaysia to North Australia and the Solomons and Vanuatu Islands. The species in Southeast Asia are usually a part of the primary and secondary forest vegetation either as large trees or as shrubs/smaller trees in the understorey. Some species are scrambling and one is reported to be a climber. Some different species seem to be restricted to a certain type of habitat, e.g. Bridelia cinnamomea peat swamp forests, Bridelia parvifolia sand dunes, Bridelia oligantha dry savannahs. The species occur from the sea level up to 1800 m, but in sect. Scleroneurae there are several species growing only at lower altitude. Currently 119 subspecies, varieties, forms, and cultivars are recognised within the genus Bridelia (Table 1). Bridelia brideliifolia Pax. Bridelia cathartica Berthol. f. f. fischeri (Pax.) Bridelia cathartica Berthol. f. var. melanthesoides (Baill.) Bridelia cathartica Berthol. f. f. niedenzui (Gehrm) Bridelia duvigneaudii J. Leonard Bridelia ferruginea Benth. Bridelia fischeri Pax. Bridelia katangensis J. Leonard Bridelia melanthoides (Baill.) J. Leonard Bridelia micrantha Hochst. Baill. Bridelia mildbraedii Gehrm. Bridelia mollis Hutch. Bridelia neogoelzea Gehrm. Bridelia niedenzui pilosa Gehrm. Bridelia pervilleana Baill. Bridelia scleroneuroides Pax. Bridelia zanzibariensis Vatke & Pax. 3. Metabolites occurring in Bridelia species Here we review the most important metabolites found in different parts of Bridelia species (Fig. 1). Some triterpenes occur in different parts of Bridelia species: friedelin (15) and friedelan3-␤-ol (18) have been found in Bridelia monoica leaves and in Bridelia ovata branches (Hui and Fung, 1968; Boonyaratavej et al., 1992). 24-Methyl-lanosta-9(11)-25-dien-3-one (19) and 24,24dimethyllanosta-9(11)-25-dien-3-one (20) are present in Bridelia tomentosa roots and in Bridelia ovata branches (Boonyaratavej, 1990; Boonyaratavej et al., 1992). It is interesting to note the presence of lignans in the genus Bridelia: 5′ -demethoxy-␤-peltatin-5-O-␤-d-glucopyranoside (7) and ␤-peltatin-5-O-␤-d-glucopyranoside (8) isolated from Bridelia ferruginea roots, exhibited antitumor activity (Rhashid et al., 2000), while the new lignan glycoside bridelioside, the known neolignan Bridelia scleroneura Müll. Arg. Bridelia fischeri Pax. Pentameria melanthesoides (Baill.) Bridelia niedenzui Gehrm. Bridelia mollis Hutch. Bridelia ferruginea Benth. Bridelia katangensis J. Leonard Bridelia katangensis J. Leonard Bridelia mollis Hutch. Bridelia cathartica Berthol.f Bridelia fischeri var. lingelsheimii (Gehrm.) Hutch. Bridelia lingelsheimii Gehrm Bridelia ferruginea Benth. Bridelia melanthoides (Baill.) Klotzsch Pentameria melanthoides (Baill.) Bridelia micrantha var ferruginea (Benth.) Mull. Arg. Bridelia abyssinica Pax. Bridelia mildbraedii Gehrm. Bridelia zanzibariensis Vatke & Pax. Candelabria micrantha Hochst. Baill. Bridelia duvigneaudii Wilki. Bridelia scadens Wilki. Bridelia stipularis Blume. Bridelia ferruginea Benth. Bridelia katangensis J. Leonard Bridelia neogoetzea Gehrm. Neogoetzea brideliifolia Pax. Bridelia fischeri Pax. Bridelia niedenzui var. pilosa Gehrm. Bridelia scleroneura Müll. Arg. Bridelia berneriana Baill. Bridelia pervilleana var. humbertii Leandri Bridelia angolensis var. nitida Beille, Bridelia paxii Gehrm., Bridelia scleroneura var. barteri Gehrm, var. togoensis Gehrm., Bridelia scleroneuroides var. elliptica Gehrm., var. typica Gehrm., Tzellemtinia nervosa Chiov. Bridelia abyssinica Pax. Bridelia mildbradii Gehrm. Candelabria micrantha Hochst. Baill. Synonyms and botanical references Bridelia (‘Briedelia’) Willd., Sp. Pl. 4 (1806) 978; corr. Spreng., Anleit. Kenntn. Gew. ed. 2, 2 (1818) 887; Müll. Arg. in DC., Prodr. 15, 2 (1866) 492; Hook. f., Fl. Brit. India 5 (1887) 267; Gehrm., Bot. Jahrb. Syst. 41, Beibl. 95 (1908) 1; Jabl. in Engl., Pflanzenr. IV.147.viii (1915) 54; Ridl., Fl. Malay Penins. 3 (1924) 183; Gage, J. Asiat. Soc. Bengal. 75 (1936) 484; Backer & Bakh. f., Fl. Java 1 (1964) 475; Airy Shaw, Kew Bull. 26 (1972) 227; Whitmore, Tree Fl. Malaya 2 (1973) 74; Airy Shaw, Kew Bull. Add. ser. 4 (1975) 63; Kew Bull. Add. ser. 8 (1980) 43; Kew Bull. 36 (1981) 272; Kew Bull. 37 (1982) 10; Enum. Euphorb. Philipp. Isl. (1983) 11; G.L.Webster, Regnum Veg. 129 (1993) 153; Ann. Missouri Bot. Gard. 81 (1994) 39; S. Dressler, Taxon 45 (1996) 337, nom. cons. prop.; Blumea 41 (1996) 273; Radcl.-Sm., Gen. Euphor. (2001) 19. — Lectotype species (G.L. Webster, 1993): Bridelia scandens (Roxb.) Willd. [Bridelia stipularis (L.) Blume]. Table 2 Ethnomedicinal properties and phytochemicals constituents of Bridelia species. Species Plant part used Traditional use Chemical compounds identified/pharmacological activities References Bridelia atroviridis Bark leaves Bridelia balansae Leaves Aphrodisiac, venereal diseases, purgative, coughs, asthma, caries Bronchitis Saponins, tannins, antimicrobial activity, cardiovascular activity Balansenate I (9), II (10), Bridelone (11), Bridelonine (12) Abbiw (1990), Agyare et al. (2006), Corallo et al. (1997) and Neuwinger (2000) Tsai et al. (2003) Bridelia brideliifolia Twig bark, root, leaves Bridelia cathartica Roots, leaves, stem bark Bridelia crenulata Bark Bridelia ferruginea Fruit leaves stem bark roots Bridelia glauca f. balansae Leaves Bridelia grandis Bark, leaves Oral cavity affection purify breast Bridelia micrantha Bark, leaves, roots Bridelia mollis Bridelia moonii Bridelia monoica Root Bark Leaves, stems roots Gastro-intestinal ailments, painful joints, retained placenta, diabetes mellitus, syphilis prehepatic jaundice, tape worm abdominal pain, conjunctivitis, headache, scabies, bloody diarrhoea, dysentery, emetic, wound infection, coughs, threadworms, tonic for children, sore eyes, epigastric pain, relief of headache, purgative Diarrhoea, worms Bridelia ndellensis Bridelia ovata Stem bark Leaves stem bark Fever, rheumatism, diarrhoea, diabetes, coughs Laxative, expectorant, astringent Bridelia pervilleana Leaf Headache Rheumatism pains, intestine disorders, dysentery, diabetes, thrush, epilepsy, infectious diseases, including sexually transmitted diseases, skin diseases and eruption, skin cancer, cystitis, antimicrobial activity, anthelmintic for roundworm, bladder trouble anti-inflammatory properties, antidote for arrow poison, skin ailments, rashes, coughs, diuretic, fever, edema, anemia, dyspepsia, asthma, amebiasis, gonorrhoea, paralysis, candida mycosis, impotence, liver problems, purgative, chickenpox, stomach pain, toothache Lack of appetite Neuwinger (2000) Anthocyanins, flavonoids, tannins, Anti-anemia for its high amount of Iron Watt and Breyer-Brandwijk (1962), Hedberg et al. (1983), Chhabra et al. (1990), Ouma et al. (1997) and Neuwinger (2000) Luteoforol (3′ ,4′ ,4,5,7-pentahydroxydroxyflavon) (13) Tannins, gallocatechin-(4′ -O-7) epigallocatechin (1), flavonoids and biflavonoids, caffeoylesters, anticomplement, antioxidant, antiviral, diabetes, anti-inflammatory, antimicrobial activity, effects on rat bladder smooth muscle, quercetin (2), quercetin-3-neohesperidoside (3), rutin (4), myricetin-3-glucoside (5), myricetin-3rhamnoside (6), 5′ -demethoxy-␤-peltatin-5-O-␤d-glucopyranoside (7), ␤-peltatin-5-O-␤-d-glucopyranoside (8) Ramesh et al. (2001a,b) Bridelionoside, bridelioside, (7R,8S)-5-methoxydihydrodehydrodiconiferyl alcohol 4-O-␤-glucopyranoside glochidioboside Antimicrobial activity against oral streptococci, antitrypanosomal and antiplasmodial activity Taraxerol (14), gallic and ellagic acid, friedelin (15), delphinidin (16), methyl salicylate, anti-diarrhoeal activity, antiplasmodial activity, weak cytotoxic activity Sueyoshi et al. (2006) and Sueyoshi et al. (2007) Glochidone (17) Stigmasterol, sitosterol, friedelan-3-␤-ol (18), Glutin-5-en-3-␤-ol, Friedelin (15) Hypoglycemic effect 24-Methyl-lanosta-9(11),25-dien-3-one (19), 24,24-dimethyl-lanosta-9(11)-25-dien-3-one (20), campesterol, stigmasterol, ␤-sitosterol, friedelin (15), friedelan-3-␤-ol (18), trans-triacontyl 4-hydroxy-3-methoxycinnamate Cimanga et al. (1999, 2001), Tona et al. (1998), Adebayo and Ishola (2009), Abubakar et al. (2007), Pieters and Vlietinck (2005), Talla et al. (2002), Ampofo (1979), Iwu (1980, 1983), Akinpelu et al. (2000), Talla et al. (2002), Olajide et al. (2003), Pedersen et al. (2009), Magassouba et al. (2007), Onoruvwe et al. (2001), Akinpelu et al. (2000), Onoruvwe et al. (2001), Olajide et al. (1999, 2003), Olajide and Makinde Modupe (2000), Rhashid et al. (2000), Neuwinger (2000) and Oliver-Bever (1986) Ngueyem et al. (2008), Atindehou et al. (2004) and Neuwinger (2000) Watt and Breyer-Brandwijk (1962), Lin et al. (2002), Steenkamp (2003), Ajaiyeoba et al. (2006), Gradé et al. (2009), Gbolade (2009), Abo et al. (2008), Ssegawa and Kasenene (2007), Clarkson et al. (2004), Hamill et al. (2003) and Neuwinger (2000) T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 Stimulate digestion, emetic, vaginal prolapsed, purgative, elephantiasis, oxytocic, insanity, gastointesintal problems, migraine Anemia, asthma, constipation, anorexia, fever, cardiac pains, amoebic dysentery, hemorrhoids, female and male infertility, coughs, aphrodisiac, epigastric pain, malaria, rectal prolapsed, headache, epilepsy, kidney pain, purgative Infertility Neuwinger (2000) Carpenter et al. (1980) Hui and Fung (1968) and Roosita et al. (2008) Sokeng et al. (2005) and Neuwinger (2000) Boonyaratavej et al. (1992) Neuwinger (2000) 341 Root Leaves Leaves roots Bark, leaves, Roots Bridelia scleuroneuroides Bridelia siamensis Bridelia stipularis Bridelia tomentosa glycoside (7R,8S)-5-methoxydihydrodehydrodiconiferyl alcohol 4O-␤-d-glucopyranoside and glochidioboside have been isolated from Bridelia glauca leaves (Sueyoshi et al., 2007). Bark and leaves are particularly rich in phenolic compounds: gallic acid, ellagic acid, anthocyanidin and delphinidin (16) have been found in Bridelia micrantha bark (Pegel and Rogers, 1968), luteoforol (3′ ,4′ ,4,5,7-pentahydroxyflavone) (13) has been isolated from Bridelia crenulata bark (Ramesh et al., 2001a,b), gallocatechin(4′ -O-7)-epigallocatechin (1) has been found in Bridelia ferruginea bark (De Bruyne et al., 1997), while rutin (4) and quercetin (2), are present in Bridelia ferruginea leaves (Addah-Mensah and Achenbach, 1985; Addah-Mensah and Munenge, 1989) and myricetin glycosides (5) and (6) and isoflavone in Bridelia retusa leaves (Madhavi Adhav et al., 2002). Compounds such as glochidone (17) (Carpenter et al., 1980), balansenate I (9) and balansenate II (10) (Tsai et al., 2003) have been found in the genus Bridelia for the first time during this research. 4. Medicinal uses Bark, roots and leaves of at least ten Bridelia species are used in African and Asian traditional and local medicines for treating several ailments including sexual diseases (Bridelia atroviridis), bronchitis (Bridelia balansae), anemia (Bridelia cathartica), intestine disorders and painful joints (Bridelia michranta), dental caries (Bridelia grandis), fever, diabetes and diarrhoea (Bridelia ndellensis), rheumatism (Bridelia retusa), rheumatism, abdominal pain and arthritis (Bridelia sclereoneura), fever (Bridelia tomentosa). The best studied species—Bridelia ferruginea—is used for bladder troubles, diabetes, dysentery, rheumatism pain and for its antimicrobial activity. Despite the very wide range of biological activities exhibited, indicating that some of these plants can be exploited for the development of novel phytopharmaceuticals, literature data concerning controlled clinical studies are limited. 4.1. Bridelia ferruginea Benth. Colic, febrifuge (−)-Ovatolide (27) Bridelyl alcohol, phlobatannin, taraxenone 24-Methyl-lanosta-9(11),25-dien-3-one 19, 24,24-dimethyl-lanosta-9(11)-25-dien-3-one 20 Bark, leaves, roots, twig bark, Bridelia scleuroneura Watt and Breyer-Brandwijk (1962) Delgado and Clardy (1993) Sengupta and Ghosh (1963) and Desai et al. (1976) Boonyaratavej (1990) Stomach pain, purgative, diarrhoea, intestinal disorders, liver problems, female sterility, whooping cough, cardiac problems Rheumatism, arthritis, abdominal pain, hernia, retained placenta, headache, wounds, mouthwash, epilepsy, mental disorders, toothache, syphilis, stomach pain, diarrhoea, peritonitis, anemia, hemorrhoids, purgative, nervousness in newborn Abdominal pains, indigestion Leaves, bark, plant powder Bridelia ripicola Dimo et al. (2006), Tabuti et al. (2003) and Gradé et al. (2009) Jayasinghe et al. (2003) Isoflavone, 4-[(E)-6-methyl-4-oxohept-2-en-2-yl)] benzoic acid (21), 4-[(E)-6-methyl-4-oxohept-2,5-dien-2-yl)] benzoic acid, 4-[(R)-6-methyl-4-oxohept-5-en-2-yl)] benzoic acid (22), 4-[(R)-6-methyl-4-oxoheptan-2-yl)] benzoic acid (23), (−)-isochaminic acid (24), 5-allyll1,2,3-trimetoxy-benzene (elemicin) (25), (+)-sesamin (26), 4-isopropylbenzoic acid, cyanogenic glycosides, triterpenes, ketone and tannins Rheumatism antifungal contraceptive wounds dysentery Roots bark leaves Bridelia retusa Antinociceptive and anti-inflammatory activity References Chemical compounds identified/pharmacological activities Traditional use Plant part used Jain et al. (2004), Ayyanar and Ignacimuthu (2005) and Kshirsagar and Singh (2001) Neuwinger (2000) T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 Species Table 2 (Continued ) 342 Bridelia ferruginea it is well known in many African countries and appears to be the most studied species both with respect to its traditional and local uses and for its pharmacological properties. It is a shrub commonly growing up to a height of 45 feet in the Savannah or in open spaces of coastal districts. Bark, roots, fruits and leaves are used mainly as decoctions. They are ingredients of the Yoruba agbo infusion and are used in the preparation of popular mouthwashes and as a remedy for thrush in children. The roots are used in Togo externally for the treatment of skin diseases and eruptions (Oliver-Bever, 1986). In Nigeria Bridelia ferruginea is used against arthritis, contusion, distortions, bites, burns, as antidote to arrow poison and against diabetes. Preliminary clinical evaluation of leaf extracts on diabetes mellitus was conducted on local albino rats. The blood glucose level was determined by the glucose oxidase method 1 h after injection or oral administration of the leaf extracts. The methanol and aqueous extracts significantly lowered the fasting blood sugar (from 250 mg% to a normal level <120 mg%) but failed to protect the animals against alloxan induced diabetes (Iwu, 1980). Along the west coast of Africa aqueous infusions of the leaves are used for the treatment of chronic diabetes particularly in cases where ketosis has set in. Clinical evaluation was conducted on 12 volunteers subjects pre-screened and certified as diabetic by the resident physician. They consulted herbalists when they failed to obtain satisfactory relief from allopathic medication and needed frequent insulin injection. Each patient received an average of one T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 wine glass-full of extract (about 30 ml) daily. The treatment scheduled was maintained for at least 8 weeks and no intake of ethanol or drugs was permitted. In the same study, the glucose tolerance test was performed on rats of either sex (200–250 g) fasted overnight before the administration of pre-treatment and treatment agents. Methanol extract was given at a dose of 50 mg/kg as a suspension with methylcellulose in saline. Alloxan was administered at a dosage of 60 mg/kg. Blood glucose was analyzed by the glucose oxidase method. The results of the clinical evaluation of patients 343 receiving treatment from a local healer showed that extracts of Bridelia ferruginea in daily doses effectively decreased hyperglycaemia of diabetes. In 8 of the 10 patients monitored the blood sugar was lowered from average of 250–120 mg%. Patients 11 and 12 were excluded because they were selected for the single-blind cross-over studies as controls. The anti-diabetic activity of Bridelia ferruginea could be attributed to a possible role in the release or activation of endogenous insulin, since the drug is more active in rats with intact ␤-cells than in rats with ␤-cell damaged caused by Fig. 1. Some characteristic chemical structure of compounds isolated from the reported Bridelia species. 344 T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 Fig. 1. (Continued ) . alloxan. Tannins, flavonoids and biflavonoids based on apigenin and kaempherol moieties were isolated together with their glycosides from the methanolic extract but it is not clear which of these compounds is responsible for the anti-diabetic properties of this plant (Iwu, 1983). The anti-inflammatory profile of the stem bark aqueous extract was investigated in vivo and in vitro. The extract exhibited strong topical anti-inflammatory effect shown as inhibition of croton oilinduced ear edema in mice, and reduced hind-paw swelling and growth retardation in the adjuvant-induced arthritis model in rats, following oral administration at 10, 20, 40 or 80 mg/kg. The extract (10–80 mg/kg, p.o.) caused an inhibition of increase in vascular permeability in both cyclophosphamide-induced hemorrhagic cystitis and acetic acid-induced vascular permeability in rats and mice, respectively. Bridelia ferruginea produced stabilization of erythrocytes exposed to heat and stress-induced lysis. In addition to its anti-inflammatory property, Bridelia ferruginea exhibited some antipyretic effect, by lowering the rectal temperatures of mice made hyperthermic by yeast, from 37.8 ◦ C to 37.2 ◦ C, 36.5 ◦ C and 36.4 ◦ C (after 60, 90 and 120 min, respectively) at 40 mg/kg, and from 38 ◦ C to 36.7 ◦ C, 36.4 ◦ C, and 36.1 ◦ C (after 60, 90 and 120 min, respectively) at 80 mg/kg. The extract is shown to produce remarkable activity in the acetic acid-induced writhing in mice, which indicates analgesic activity (Olajide and Makinde Modupe, 2000). The anti-inflammatory activity of the aqueous extract of Bridelia ferruginea stem bark was further evaluated in models which are mediated by tumor necrosis factor-alpha (TNF␣). The effect of the extract (10–80 mg/kg) was evaluated in both lipopolysaccharide (LPS-induced septic shock and LPS-induced microvascular permeability) after subcutaneous injection of LPS (1 ␮g/kg). Results showed in this study provided an evidence for a possible role for T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 TNF␣ in the anti-inflammatory effects of the stem bark extract of Bridelia ferruginea (Olajide et al., 2003). The obtained results may support the uses of this plant in the Nigerian traditional medicine. In Congo Kinshasa, the decoction of Bridelia ferruginea stem bark is used in the traditional and local medicine for diarrhoea, dysentery, intestinal disorders, female sterility, rheumatic pains, as anthelmintic for roundworm and in the treatment of cystitis (Oliver-Bever, 1986). It has been studied in vitro for the inhibition of the complement system which is well known to play an important role in the host defence system, inflammation and allergic reactions. The inhibition of the xanthine oxidase activity was evaluated by measuring the UV absorbance at 290 nm while the superoxide anion scavenging activity was detected spectrophotometrically by the nitrile method. The crude extract exhibited a dose-dependent inhibitory effect on the classical pathway of the complement system. These findings provide some evidence for the traditional use of Bridelia ferruginea for the rheumatic pain treatment in Congo Kinshasa (Cimanga et al., 1999, 2001). Moreover, the phytochemical investigation of Bridelia ferruginea stem bark led to the discovery of a biflavonoid: gallocatechin(4′ -O-7)-epigallocatechin (1). The structure was elucidated using two-dimensional NMR techniques (COSY, HMQ, HMBC); this product seems to be responsible for the stem bark anti-inflammatory activity (De Bruyne et al., 1997). In Nigeria and Ivory Coast the decoction of Bridelia ferruginea stem bark is used as a mouthwash for Candida oral thrush; in Ivory Coast only, the roots decoction is used for the treatment of gonorrhoea (Ozerov et al., 1994). The water and ethanolic stem bark extracts showed in vitro antimicrobial activities (Irobi et al., 1994) in assays against hospital strains of Staphylococcus aureus, Candida albicans, Staphylococcus epidermidis, Escherichia coli, Streptococcus lactis, Proteus vulgaris, Proteus mirabilis, Streptococcus pyogenes and Klebsiella sp. The zones of inhibition produced by the extracts in agar diffusion assays against the test microorganisms ranged from 4 to 20 mm, while the chloramphenicol antibiotic control produced zones that measured 15–36 mm. Activity showed against Staphylococcus aureus and Candida albicans may justify the use of the bark as mouthwash in Nigerian and Ivorian traditional medicine. In Cameroon, Bridelia ferruginea leaves are used for treating dysentery (Talla et al., 2002), while fruits are employed for mycotic stomatitis (Ampofo, 1979). Methanolic, ethyl acetate and hexane leaves extracts exhibited significant activity against Pseudomonas frutescens, Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Streptococcus faecalis. The activity was measured by the agar disc diffusion method and determination of minimum inhibitory concentrations (MIC), using streptomycin (10 ␮g), erythromycin (5 ␮g), tetracycline (10 ␮g), penicillin (1i.u.), chloramphenicol (10 ␮g) as references antibiotics. On the basis of the determined MICs, the effect of ethyl acetate extract against Streptococcus faecalis (5 ± 0.9 mg/ml) and Staphylococcus aureus (8 ± 1.2 mg/ml), of methanol extract against Streptococcus faecalis (9 ± 0.7 mg/ml), and of hexane extract against Bacillus subtilis and Streptococcus faecalis (8 ± 0.5 mg/ml, 4 ± 1 mg/ml), were the most interesting. The methanolic fruit extract exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria: Bacillus subtilis, Corynebacterium pyogenes, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Shigella dysenteriae, Staphylococcus aureus (Akinpelu et al., 2000). The effects of ethanol extracts of Bridelia ferruginea leaves and stem bark on purinergic neurotransmission in the rat bladder were investigated. Effects were evaluated on electrical stimulation using parallel platinum wire electrodes, concentrations of plant extracts ranging between 3 × 10−5 and 3 × 10−3 g/ml and atropine, propra- 345 nolol and prazosin (1 × 10−6 each) as antagonist cocktail. Same concentrations of plant extracts were evaluated against chemical stimulation induced by adenosine 5-triphosphate (ATP) from 1 × 10−8 and 3 × 10−4 g/ml and potassium chloride (10−3 to 10−1 M). The stem bark extract potentiated the contraction of the bladder evoked by exogenous ATP but depressed KCl-induced contractions in a dose-related pattern. The leaf extract depressed purinergic nerve-mediated contraction of the rat bladder in a dose-related fashion. This action could be attributed to blockade of purinergic neurotransmission since the leaf extract did not affect KCl-induced contractions (Onoruvwe et al., 2001). The flavonoids quercetin (2), quercetin-3-neohesperidoside (3), rutin (4), myricetin-3-glucoside (5), myricetin-3-rhamnoside (6), (Addah-Mensah and Achenbach, 1985; Addah-Mensah and Munenge, 1989) were found in the leaves extracts but there are no data on the biological activities of the isolated compounds. Methanolic leaves extracts significantly increased the uterine epithelial height by 28.08% compared with uteri of ovari-ectomized controls after 7 days of treatment but the extract was not further evaluated because of its toxicity on Ishikawa cells (Njamen et al., 2008). A bioassay-guided fractionation of a Bridelia ferruginea roots extract provided four cytotoxic lignans structurally related to podophyllotoxin; two of these, 5′ -demethoxy-␤-peltatin-5-O-␤-dglucopyranoside (7) and ␤-peltatin-5-O-␤-d-glucopyranoside (8) exhibited antitumor activity (Rhashid et al., 2000). 4.2. Bridelia atroviridis Muell. Arg. Bridelia atroviridis is a small straggly tree growing in Ghana up to 20 feet or more; the local ‘Twi’ name is ‘Opamkotorodu’. The stem is flexuous; prickly, its leaves are 6 by 2 inches, oblongelliptic, acuminate, becoming glabrous on both surfaces; the midrib is prominent on lower surface, its lateral nerves are 16–20 pairs; flowers are small, yellowish, male and female separate; auxiliary; fruits are about one-third long, black, oblong, episodic and one seeded (Irvine, 1961). The wood is dark brown, very hard and durable and it is used for building traditional houses and for fuel. Bark decoction is used as purgative, diuretic and aphrodisiac remedy and also to manage gonorrhoea and other venereal diseases. Leaves infusion is used as purgative (Abbiw, 1990). Saponins and tannins were the phytochemical constituents found in petroleum ether and methanolic leaves and stem bark extracts which showed also antifungal (Candida albicans) and antimicrobic (Escherichia coli, Bacillus subtilis, and Staphylococcus aureus) activities determined by the agar diffusion method. Using a sterile cork borer number 6, four cups were bored in the set agar and cups were labeled appropriately. Each cup was filled with 10 mg/ml of the plant extracts and 1.0 mg/ml chloramphenicol used as reference drug for the bacteria The methanolic leaves extract only showed activity against Pseudomonas aeruginosa. These results may support the traditional uses of Bridelia atroviridis in Ghana. Lyophilized decoction of the leaves was studied in the rat cardiovascular system. In vivo, the extract (15 and 30 mg/kg) caused a decrease of arterial pressure and a decrease of heart rate in anesthetized rat (ethylcarbamate 1.2 g/kg). In vitro, the extract induced dose-dependent negative inotropic and chronotropic effects in isolated rat heart. Bridelia atroviridis seemed to have a direct effect on rat heart and the extract might act through potential dependent calcium channels (Corallo et al., 1997). 4.3. Bridelia balansae Tucht. Bridelia balansae is a small tree distributed in Indo-China, South of China, Ryukyus and Taiwan. Leaves are used as anti- 346 T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 tussive for treating bronchitis. Two long-chain esters balansenate I (6,8,11-trimethyldodecanoic acid (2E)-3-methylhexadec-2-enyl ester) (9) and balansenate II (10,12,15-trimethylhexadedecanoic acid (2E)-3-methylhexadec-2-enyl ester) (10) were found in the leaves extract (Tsai et al., 2003); the structures were identified by means of EI-MS and HR-EI-MS spectroscopy, respectively. Furthermore, bridelone (11) and bridelonine (12) were identified by MS, IR and 1 H and 13 C NMR (DEPT, COSY, HETCOR, H MBC and NOESY) techniques. The same extract afforded also known adenine derivatives: 9-(3-methylbut-2-enyl)adenine, 1(3-methylbut-2-enyl)adenine, N6 -(3-methylbut-2-enyl) adenine, 3-(3-methylbut-2-enyl)adenine and adenine. As a part of these studies these known compounds were isolated for the first time from a plant. 4.4. Bridelia cathartica Bertol. f. In Northern Rhodesia Bridelia cathartica is used medicinally as a purgative (Watt and Breyer-Brandwijk, 1962). Leaves, stem bark and roots are used traditionally to treat anemia in children and pregnant women in Eastern Africa. The iron content in the different plant parts was determined using atomic absorption spectroscopy. The prominent iron content was found in the root bark (Ouma et al., 1997). These findings support the use of this plant for traditional anemia treatments. 4.5. Bridelia crenulata Roxb. Bridelia crenulata stem bark is used in India as antifertility agent and for stopping menorrhagia. The aqueous bark extract exhibited antibacterial activity against Aeromonas hydrophila, Chromobacterium violaceum, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Vibrio cholerae, Vibrio parahaemoliticus, Bacillus subtilis, Staphylococcus aureus. The agar well-diffusion method of Perez et al. (1990) was followed. About 0.3 ml each of 100% and 50% aqueous extracts and different concentrations of solvent extracts were added into the wells using sterilized dropping pipettes and allowed for diffusion at room temperature for 2 h. Ceftriaxone (30 ␮g/disc), chloramphenicol (30 ␮g/disc), erythromycin (15 ␮g/disc), novobiocin (30 ␮g/disc), trimethoprim (5 ␮g/disc) were used as standard. The aqueous extract expressed more activity to Aeromonas hydrophila (37 mm diameter of zone of inhibition), Escherichia coli (32 mm) and Staphylococcus aureus (32 mm) and moderate activity to Bacillus subtilis (21 mm). Activity against Vibrio cholerae (22 mm) was found in the methanol extract only while aqueous extract did not show any activity. The phytochemical study on methanol extract reported the presence of luteoforol (3′ ,4′ ,4,5,7pentahydroxyflavone) (13) which exhibited the same antibacterial activity as the crude alcoholic extract against the tested bacteria (Ramesh et al., 2001a,b). 4.6. Bridelia glauca Bl. f. balansae Tucht. Bridelia glauca Bl. f. balansae (Tucht.) (Phyllanthaceae), is an evergreen tree which grows up to a height of about 10 m, and it is distributed in Okinawa, Japan, Taiwan, Southern China, Indochina and the Philippines. There are no reports of the use of this species in traditional medicine, but chemical investigation performed on leaves by Sueyoshi et al. (2006) led to the isolation of six new megastigmane glucosides to which bridelionosides A–F were assigned as trivial names, respectively, along with seven known megastigmane glucosides. Their structures were determined by a combination of spectroscopic analyses and application of the modified Mosher’s method (Sueyoshi et al., 2006). Moreover, a new lignan glycoside named bridelioside and the known neolignan glycoside (7R,8S)-5-methoxydihydrodehydrodiconiferyl alcohol 4O-␤-glucopyranoside and glochidioboside were isolated also from the leaves; the structures were determined by NMR and HR-FAB-MS spectra (Sueyoshi et al., 2007). 4.7. Bridelia grandis (Pierre ex Hutch) Bridelia grandis (Pierre ex Hutch) (Phyllanthaceae), is used in Cameroon by pygmies Baka, an indigenous group well known for their widespread use of traditional medicine. The bark decoction is used for oral cavity affection. Stem bark water, methanol and mixtures methanol–water extracts were investigated for their in vitro antimicrobial properties as well as for their phytochemical constituents. The antimicrobial activity of the extracts against oral streptococci was evaluated on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) by the macrodilution method; the bacterial surface hydrophobicity was also evaluated. Water, methanol and mixtures methanol–water extracts, exhibited antibacterial activity with MIC between 0.5 and 2 mg/ml justifying the traditional use of Bridelia grandis stem bark for oral cavity affection. Preliminary phytochemical analyses were performed on the most active extract (methanolic) using appropriate tests and well established analytical screening methods, such as TLC and RP-HPLC/DAD. Data obtained indicate that tannins are the chemical family responsible for the biological activity (Ngueyem et al., 2008). Atindehou et al. (2004) investigated the antitrypanosomal and antiplasmodial activity of several plants from Côte d’Ivoire. Bridelia grandis stem bark and root showed a weak activity (IC50 20 ␮g/ml for stem bark extract and 8.2 ␮g/ml for root extract) against Trypanosoma brucei rhodesiense and IC50 >5 ␮g/ml for both extracts against Plasmodium falciparum. 4.8. Bridelia micrantha (Hochst) Baill. The use of medicinal plants for curing AIDS-related conditions is common in Africa. Nine medicinal plants have been screened, in order to assess possible antiviral effects. Crude methanol extracts of Bridelia michranta were fractionated and the fractions were tested at a concentration of 1, 10 and 100 ␮g/ml on reverse transcriptase (RT) function. The n-butanol fraction was the most active with an IC50 of 7.3 ␮g/ml against the RNA-dependent DNA polymerization (RDDP) function of HIV-1 RT (Bessong et al., 2006). The leaf sap of Bridelia micrantha is used by the Haya as an application to sore eyes; the Shambala use the roots as a remedy for severe epigastric pain while the Zigula rub a preparation of the powdered root, made with oil or butter, into the scalp for the relief of headache. In both East and West Africa the root is used as purgative (Watt and Breyer-Brandwijk, 1962). In South Africa, Bridelia micrantha stem bark is used in traditional medicine for gastrointestinal ailments, paralysis and painful joints also (Lin et al., 2002). Steenkamp (2003) reported the use of the bark as abortifacient with a potentially toxic effect probably due to the presence of delphinidin and methyl salicylate. In five districts of Lagos state of Nigeria Bridelia micrantha stem bark is used in traditional medicine for treating diabetes (Gbolade, 2009); in South Western Nigeria a leaf decoction is used traditionally as part of recipe for the management of diabetes mellitus (Abo et al., 2008). In the Sango bay ecosystem in Rakai district, central Uganda, a decoction of bark and leaves is indicated for treating syphilis and the bark for pre-hepatic jaundice also (Ssegawa and Kasenene, 2007). Clarkson et al. (2004) reports on the in vitro antiplasmodial activity of 134 plant taxa native to or naturalised in South Africa. Bridelia micrantha twigs showed an IC50 of 59.3 ␮g/ml against Plasmodium falciparum D10. T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 Ajaiyeoba et al. (2006) reported the cytotoxicity effects of 20 plants used in Nigerian as antimalarials. The 50% lethal concentration (LC50 value) at 95% confidence interval was calculated with the brine shrimp lethality assay for each plant methanol extract, using a non-linear regression curve, using the Graph pad prism statistical software. Bridelia micrantha resulted the least toxic plant extract with LC50 value >9.0 × 106 ␮g/ml). Taraxerol (14) and friedelin (15) were identified as the major constituents of Bridelia micrantha stem bark hexane extract while gallic and ellagic acid were found as the major components of ether and acetone extracts, respectively. The anthocyanidin delphinidin (16) was identified in the fresh leaves hot acid extract and the presence of caffeic acid was also reported (Pegel and Rogers, 1968). The occurrence of these polyphenolic compounds in Bridelia micrantha may support its ethnomedical use for pain treatment. 4.9. Bridelia moonii Thw. There is no report of the use of Bridelia moonii in traditional medicine, but this plant is interesting for the presence of glochidone (17) a compound found in the Bridelia mooni bark benzene extract and for the first time outside the Glochidion genus. The structure was determined by 1 H NMR (Carpenter et al., 1980). 4.10. Bridelia monoica (L.) Merr. The only report concerning the use of Bridelia monoica in traditional medicine is in a rural Sundanese community, Sukajadi village, where roots are used for the lack of ‘appetite’ (Roosita et al., 2008). The occurrence of triterpenoids and steroids was observed in different parts of Bridelia monoica but so far no traditional use has been described. Friedelin (15), friedelan-3-␤-ol (18), glutin-5-en3-␤-ol and a mixture of stigmasterol and sitosterol were found in the leaves. Fridelan-3-␤-ol (18) and stimagsterol are present also in the stems (Hui and Fung, 1968). 4.11. Bridelia ndellensis Beille. Bridelia ndellensis is commonly used in Cameroon against fever, rheumatism, diarrhoea and diabetes. Stem bark ethanol extract did not show hypoglycemic effect in type 1 diabetic rats, while ethyl acetate/dichloromethane fractions lowered the glucose levels in type 2 diabetic rats significantly (Sokeng et al., 2005). These findings may support the use of Bridelia ndellensis in traditional medicine. 4.12. Bridelia ovata Decne. Bridelia ovata is a small tree called “Ma-ga” in the Thai traditional medicine, the decoction of dried leaves is utilized as expectorant and laxative, while the stem bark decoction for its astringent properties (Boonyaratavej et al., 1992). There is no report of a chemical investigation about Bridelia ovata leaves. The following compounds were isolated from the dried branches’ chloroform extract: 24-methyllanosta-9(11)-25-dien-3-one (19), 24,24-dimethyIlanosta-9(11),25-dien-3-one (20), friedelin (15), friedelan-3-␤-ol (18), ␤-sitosterol, stigmasterol, campesterol and trans-triacontyl 4-hydroxy-3-methoxycinnamate. 347 and Ignacimuthu, 2005). In Karnataka state, districts of Mysore and Coorg, a bark infusion is used for treating dysentery (Kshirsagar and Singh, 2001). Many active products were isolated from the stem bark: new bisabolane sesquiterpenes, 4-[(E)-6-methyl-4-oxohept-2-en-2-yl)] benzoic acid (21), 4-([R)-6-methyl-4-oxohept-5-en-2-yl)] benzoic acid (22), 4-[(R)-6-methyl-4-oxoheptan-2-yl)] benzoic acid (23) and (−)-isochaminic acid (24), together with the known 4-[(R)6-methyl-4-oxoheptan-2-yl)] benzoic acid (ar-todomatuic acid), 5-allyl-1,2,3-trimethoxy-benzene (elemicin) (25), (+)-sesamin (26), and 4-isopropylbenzoic acid (cumic acid). All the above mentioned compounds showed interesting fungicidal activity against Cladosporium cladiosporensis (a plant-pathogenic fungus), except for elemicin (Jayasinghe et al., 2003). Bridelia retusa was screened for the presence of phenolics, condensed tannins, gallotannins, ellagitannins, fiber, alkaloids, saponins and cyanogenic glycosides. Saponins are present in all plant parts (Mali and Borges, 2003), cyanogenic glycosides could be found in young leaves only while all the other compounds were not found. Leaves are used in Ayurvedic Medicine for the treatment of urinary tract infections while bark is given orally to women to develop sterility and as contraceptive (Jain et al., 2004). Simple isoflavone was isolated from leaves and its structure elucidated by IR and NMR spectroscopy. Isoflavone shows strong antimicrobial activity against both Gram-positive and Gramnegative bacteria (Madhavi Adhav et al., 2002) and these results may explain and support the use of Bridelia retusa leaves in traditional medicine as antibacterial. 4.14. Bridelia scleroneura Mull-Arg. Bridelia scleroneura bark is used in the traditional medicine in Cameroon to relieve abdominal pains, contusions, arthrosis and inflammations. The antinociceptive and anti-inflammatory effects of ethyl acetate stem bark extract were tested. The putative analgesic effect of the plant extract was examined in abdominal constriction, hot plate, formalin and on pain using tail immersion mouse models and in carrageenan-induced paw edema in rats. The extract (150–600 mg/kg) exhibited a dose-dependent analgesic effect (46.27–78.97%) in acetic acid-induced abdominal constriction in mice; increased the pain latency of nociceptive response to thermal stimuli at the higher dose of 600 mg/kg; induced significant dose-dependent reduction of the nociception in both early and late phases of the formalin test. The extract at the dose of 300 mg/kg, increased significantly, by 63.70% and 52.01% the tail-immersion latency time, 1 and 2 h post-dosing. In the carrageenan test, Bridelia scleroneura (150–600 mg/kg, p.o.) had dose-dependent and significant effects at different time intervals. Indometacin (10 mg/kg) was used as a standard drug. These results showed that Bridelia scleroneura ethyl acetate extract possesses peripheral and central analgesic properties as well as anti-inflammatory activity on acute inflammatory processes which are profitable, since most inflammatory conditions are usually associated with pains of varying intensity (Dimo et al., 2006). However until now no chemical investigation has been reported. In Bulamogi county in Uganda a tea made with Bridelia scleroneura bark is used for treating hernia (Tabuti et al., 2003). 4.15. Bridelia scleroneuroides Pax. 4.13. Bridelia retusa (L.) Sprengel. Bridelia retusa is a moderate size tree growing in Sri Lanka. Stem bark and roots are used by natives to treat rheumatism and as astringent agents (Jayasinghe et al., 2003). The Kani of the Kouthalai region in Southern India use a paste prepared from leaves along with the leaves of Curculigo orchioides and the oils of castor, coconut and gingelly applied externally to cure wounds (Ayyanar This species is taken by the Ha and Bondei for the relief of abdominal pains and indigestion (Watt and Breyer-Brandwijk, 1962). 4.16. Bridelia siamensis Craib. Bridelia siamensis is a Thai medicinal plant used as laxative, febrifuge and astringent. Phytochemical studies led to the isolation 348 T.A. Ngueyem et al. / Journal of Ethnopharmacology 124 (2009) 339–349 of a tetracyclic indole derivative (−)-ovatolide (27). The structure is unusual and Delgado achieved its total synthesis in order to obtain significant material for biological studies (Delgado and Clardy, 1993). 4.17. Bridelia stipularis Blume. Bridelia stipularis is distributed in the warm regions of India. Bark decoction is used in the traditional medicine for the treatment of asthma, intestinal worms and cough, while leaves are used against colics. Tannins were isolated from the bark and they may be the active compounds or contribute to the activity. Moreover, investigations on the leaves led to isolate a fatty alcohol, C22 H46 O, named bridelyl alcohol besides fatty acids and a phlobatannin (Sengupta and Ghosh, 1963). Furthermore, taraxenone was isolated from roots hexane extract (Desai et al., 1976). 4.18. Bridelia tomentosa Bl. (syn. Bridelia monoica Merr.) Bridelia tomentosa is very similar to Bridelia ovata but it is called “Khon non” in Thai traditional medicine. Leaves and stem bark decoction are used against colitis. Roots appear to be a rich source of terpenoids. The triterpenoids 24-methyl-lanosta-9(11), 25-dien3-one (19) and 24,24-dimethyl-lanosta-9(11)-25-dien-3-one (20) were isolated and their structures determined by IR and 1 H NMR spectroscopy (Boonyaratavej, 1990). It is interesting to note that this species, reported as synonymous of Bridelia monoica, shows a different metabolites composition. be hypothesized with their traditional uses. Concerning toxicological information, no significant data are reported. A weak cytotoxic activity is described only for Bridelia micrantha. A critical assessment of the results presented in this review may provide useful clues to promote further investigations for the development of new phytopharmaceuticals from the genus Bridelia. 6. Conclusion Literature actually reports chemical investigations and pharmacological activities of 16 species of Bridelia only, out of the 60 known. It is important to remember that so far, there are no published data concerning either the toxicity of the whole remedies and the isolated compounds from Bridelia plants. Traditional medicine practice must be validated not only by tests in vitro and in vivo, as reported, but also by clinical trials; moreover, stability and toxicity of isolated chemical compounds and traditional remedies should be determined. Data collected in this review illustrate that despite the diversity of the genus and the numerous phytochemical metabolites found, Bridelia species have not been fully explored concerning either safety and toxicity aspects. Possible applications in clinical research are here described but further investigations on phytochemical discovery and subsequent screening are needed for opening new opportunities to develop pharmaceuticals based on Bridelia constituents. References 5. Critical assessment of ethnomedicinal properties, pharmacological activities and chemical compounds found in Bridelia spp. Of the approximately 60–70 species of Bridelia only a few species have been studied so far under different aspects. The ethnomedical uses of only 13 species have been reported and the pharmacological activities of only 10 species have been studied so far. The phytochemical studies led to the identification of a large number of polyphenols, triterpenes, glycosides and lignans. Table 2 reports ethnomedicinal properties, phytochemical constituents and pharmacological activities of all the Bridelia species considered in this review, correlated with the part of the plant under study. Almost all the Bridelia spp. are used traditionally for their antiinflammatory and antimicrobial properties (e.g. Bridelia ferruginea, Bridelia grandis, Bridelia ndellensis, Bridelia retusa), some of them for intestinal disorders (e.g. Bridelia ferruginea, Bridelia michranta, Bridelia scleuroneura, Bridelia tomentosa) and few of them for different ailments (e.g. Bridelia balansae for bronchitis, Bridelia crenulata for infertility). Often these results give a validation of the uses known in popular medicine as reported for each species. For Bridelia cathartica, Bridelia grandis and Bridelia michranta the traditional uses are confirmed by pharmacological tests. It is interesting to note that polyphenols, some of the chemical components identified in Bridelia michranta, are considered relevant to the main biological activity. Since these compounds well known for example for their antimicrobial, anti-inflammatory and antioxidativeproperties, were found almost in all the Bridelia barks, they can be considered the active metabolites responsible for the activities reported in the traditional use (e.g. Bridelia atroviridis, Bridelia ferruginea, Bridelia retusa, Bridelia stipularis). 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