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Brucea antidysenterica J.F.Mill.

Protologue
Icon. anim. plant. 5: t. 25 (1779).
Family
Simaroubaceae
Origin and geographic distribution
Brucea antidysenterica occurs widely in tropical Africa, from Guinea and Nigeria east to Ethiopia and south to Angola, Malawi and Zambia.
Uses
As its name suggests, Brucea antidysenterica is of value in traditional medicine for the treatment of dysentery. The bark, fruit and roots are widely used against dysentery, as an anthelmintic and to treat fever. The bark, fruit, seeds, leaves and roots (sometimes boiled) are used as a remedy for diarrhoea, indigestion and stomach-ache. The leaves and roots are cooked with meat, or infused with milk (for children) to relieve asthma.
Wounds and skin complaints, such as those caused by leprosy and scrofula, are treated with ointments made from the leaves and twigs mixed with ghee or butter, or from the ripe fruits mixed with honey. Preparations of the roots are used on sores caused by sexually transmitted diseases, while the leaves and seeds are used to treat cancerous skin tumours. The fruits, leaves and twigs are also used in ethnoveterinary medicine on skin galls and sores, and the powdered leaves to relieve bloating and colic in cattle. The roots are used to treat rabies.
In Eritrea the wood is used as firewood and for roof construction.
Properties
The potent anticancer properties shown by extracts of Brucea antidysenterica have attracted much research attention in recent decades. Its bioactivity is attributed to the presence of quassinoid and canthin alkaloids.
Quassinoid compounds known as bruceolides, notably bruceantin and bruceanic acids, have been isolated from the leaves and stem bark. Bruceantin has shown anticancer activity against B16 melanoma, colon 38, and L1210 and P388 leukaemia in mice. However, in subsequent clinical trials no objective tumour regressions were observed and clinical development was terminated. Recently, the activity of bruceantin was studied with a number of leukaemia, lymphoma and myeloma cell lines. Treatment of HL-60 and RPMI 8226 cell lines induced apoptosis involving the caspase and mitochondrial pathways. An in-vivo study using RPMI 8226 human-SCID xenografts demonstrated bruceantin-induced regression in early as well as advanced tumours; these responses were facilitated in the absence of overt toxicity. In addition to their antineoplastic activity, many bruceolides present in Brucea antidysenterica are highly effective against Entamoeba histolytica (IC50 of bruceantin = 0.018 μg/ml), and the malaria parasite Plasmodium falciparum (IC50 of bruceantin = 0.0008 μg/ml). Root extracts are reportedly active against Plasmodium gallinaceum in birds. Quassinoids from Brucea antidysenterica have exhibited weak anti-tuberculosis activity in vitro, whilst their anti-HIV potential is marred by high cytotoxicity.
Quassinoids are characteristic of the Simaroubaceae; they give the bark of Brucea antidysenterica a distinctive bitter taste.
Canthin alkaloids, present in the root bark of Brucea antidysenterica, have anticancer and antimicrobial properties. Some of them have been produced by cell suspension cultures of Brucea antidysenterica.
The fruit is bitter and reportedly toxic to livestock, especially sheep. It contains about 22% oil. A yellow dye in the fruit endocarp is non-soluble in water. Crystals of calcium oxalate are present in the bark, leaves and roots.
Description
Monoecious shrub or small tree up to (7–)10(–15) m tall, sometimes branching from the base; bark grey to grey-brown with heart-shaped leaf-scars; young stems terete, with red-brown hairs. Leaves alternate, usually crowded at the end of younger twigs, 10–65 cm long, imparipinnately compound with 2–6 pairs of leaflets; stipules absent; petiole up to 15 cm long, with red-brown hairs; petiolules 1–9 mm long, up to 35 mm on terminal leaflet; leaflets narrowly oblong to narrowly ovate, 3–18 cm × 1.5–8 cm, base asymmetric and rounded, apex pointed, glossy dark to pale green, with red-brown hairs. Inflorescence an axillary, erect, red-brown hairy panicle 5–35 cm long, male and female flowers in separate inflorescences in compact clusters. Flowers unisexual, regular, (3–)4(–5)-merous; pedicel 1–8 mm long; sepals almost free, oblong to ovate, 2–3 mm × c. 1.5 mm, acute, pale green, red-brown hairy; petals oblong to ovate, 1.5–3 mm × 1–1.5 mm, pale green, red-brown hairy outside; male flowers with white to pale yellow stamens; female flowers with 4–5 carpels free or joined at base, c. 1–2.5 mm × 1–3 mm, sometimes hairy, stigmas c. 1 mm long, free, bent outwards in a cruciform arrangement. Fruit composed of 1–4 drupe-like ellipsoid mericarps, 9–14 mm × 6–8 mm, apex pointed, shiny pale green, ripening yellow-orange to dark red, each mericarp 1-seeded. Seeds ovoid, 8–9 mm × 5–6 mm, apex pointed, pale brown, with a large red to dark-brown spot.
Other botanical information
Brucea comprises 6 species in the Old World tropics, of which 5 occur naturally in tropical Africa. Brucea javanica (L.) Merr. has been introduced in DR Congo for its medicinal properties, which are similar to those of Brucea antidysenterica. It is found near villages and has become naturalized. The West African lowland species Brucea guineensis G.Don is reported to be threatened as a result of medicinal use. No details on its use are documented, but bruceantin and several other quassinoids have been isolated from the stem bark.
Growth and development
Vegetative growth, flowering and fruiting of Brucea antidysenterica continue throughout the year, even in the dry season.
Ecology
Brucea antidysenterica occurs in montane forests, in forest margins and commonly in secondary vegetation. It is found at altitudes of 1000–3700 m, but most frequently at 1750–2500 m altitude.
Propagation and planting
Brucea antidysenterica can be readily propagated from seed and is sown on site. An alternative method of propagation is transplanting wildlings. Seed can be stored at room temperature for over a year.
Diseases and pests
Brucea antidysenterica has been recorded as a host plant of the Mediterranean fruit fly, a major pest of the fruit industry.
Genetic resources
Brucea antidysenterica is widely distributed and no threats to its genetic variability are envisaged. If demand for the bark increases, it will be worthwhile closely monitoring its status and taking protective measures against non-sustainable use, including domestication.
Prospects
Bruceantin and related compounds have shown very promising anti-cancer effects. Their potency warrants further investigation as promising candidates for drug development. Bruceantin has yet to be produced synthetically. Protocols have been established for the in-vitro production of bioactive alkaloids and quassinoids from cell suspension cultures of Brucea javanica and there is potential for similar protocols using Brucea antidysenterica.
Major references
• Burkill, H.M., 2000. The useful plants of West Tropical Africa. 2nd Edition. Volume 5, Families S–Z, Addenda. Royal Botanic Gardens, Kew, Richmond, United Kingdom. 686 pp.
• Dale, I.R. & Greenway, P.J., 1961. Kenya trees and shrubs. Buchanan’s Kenya Estates Limited, Nairobi, Kenya. 654 pp.
• Gillin, F.D., Reiner, D.S. & Suffness, M., 1982. Bruceantin, a potent amoebicide from a plant, Brucea antidysenterica. Antimicrobial Agents and Chemotherapy 22: 342–345.
• Jansen, P.C.M., 1981. Spices, condiments and medicinal plants in Ethiopia, their taxonomy and agricultural significance. Agricultural Research Reports 906. Centre for Agricultural Publishing and Documentation, Wageningen, Netherlands. 327 pp.
• Kokwaro, J.O., 1993. Medicinal plants of East Africa. 2nd Edition. Kenya Literature Bureau, Nairobi, Kenya. 401 pp.
• Kupchan, S.M., Britton, R.W., Lacadie, J.A., Ziegler, M.F. & Sigel, C.W., 1975. The isolation and structural elucidation of bruceantin and bruceatinol, new potent antileukemic quassinoids from Brucea antidysenterica. Journal of Organic Chemistry 40(5): 648–654.
• Rahman, S., Fukamiya, N., Okano, M., Tagahara, K. & Lee, K.-H., 1997. Anti-tuberculosis activity of quassinoids. Chemistry and Pharmaceutical Bulletin 45: 1527–1529.
• Roberts, M.F., 1994. Brucea spp.: in vitro culture and the production of canthinone alkaloids and other secondary metabolites. In: Bajaj, Y.P.S. (Editor). Biotechnology in agriculture and forestry. Volume 26. Medicinal and aromatic plants VI. Springer-Verlag, Berlin, Germany. pp. 21–45.
• Stannard, B.L., 2000. Simaroubaceae. In: Beentje, H.J. (Editor). Flora of Tropical East Africa. A.A. Balkema, Rotterdam, Netherlands. 15 pp.
• Watt, J.M. & Breyer-Brandwijk, M.G., 1962. The medicinal and poisonous plants of southern and eastern Africa. 2nd Edition. E. and S. Livingstone, London, United Kingdom. 1457 pp.
Other references
• Abebe, D. & Hagos, E., 1991. Plants as a primary source of drugs in the traditional health practices of Ethiopia. In: Engels, J.M.M., Hawkes, J.G. & Worede, M. (Editors). Plant genetic resources of Ethiopia. Cambridge University Press, Cambridge, United Kingdom. pp. 101–113.
• Arbayah H. Siregar, 1999. Brucea javanica (L.) Merr. In: de Padua, L.S., Bunyapraphatsara, N. & Lemmens, R.H.M.J. (Editors). Plant Resources of South-East Asia No 12(1). Medicinal and poisonous plants 1. Backhuys Publishers, Leiden, Netherlands. pp. 160–163.
• Arisawa, M., Kinghorn, A.D., Cordell, G.A. & Farnsworth, N.R., 1983. Plant anticancer agents. XXIV. Alkaloid constituents of Simaba multiflora. Journal of Natural Products 46: 374–378.
• Aubréville, A., 1959. La flore forestière de la Côte d’Ivoire. Deuxième édition révisée. Tome deuxième. Publication No 15. Centre Technique Forestier Tropical, Nogent-sur-Marne, France. 341 pp.
• Chiu, C.K.-F., Govindan, S.V., Fuchs, P.L., 1994. Synthesis of 15-deoxy-16B-ethoxybruceantin and synthetic efforts towards bruceantin. Journal of Organic Chemistry 59: 311–323.
• Cuendet, M. & Pezzuto, J.M., 2004. Antitumor activity of bruceantin: an old drug with new promise. Journal of Natural Products 67(2): 269–272.
• Fernando, E.S., Gadek, P.A. & Quinn, C.J., 1995. Simaroubaceae, an artificial construct: evidence from rbcL sequence variation. American Journal of Botany 82: 92–103.
• Fong, K.-L.L., Ho, D.H.W., Carter, C.K.J., Brown, N.S., Benjamin, R.S., Freireich, E.J. & Bodey, G.P., 1980. Radioimmunoassay for the detection and quantitation of bruceantin. Analytical Biochemistry 105: 281–286.
• Fukamiya, N., Koano, M., Aratani, T., Negoro, K., Lin, Y.-M. & Lee, K.-H., 1987. Antitumor agents: LXXXVII. Cytotoxic antileukemic canthin-6-one alkaloids from Brucea antidysenterica and the structure activity relationships of their related derivatives. Planta Medica 53: 140–143.
• Guru, P.Y., Warhurst, D.C., Harris, A. & Phillipson, J.D., 1983. Antimalarial activity of bruceantin in vitro. Annals of Tropical Medicine and Parasitology 77: 433–435.
• Harris, A., Anderson, L.A., Phillipson, J.D. & Brown, R.T., 1985. Canthin-6-one alkaloids from Brucea antidysenterica root bark. Planta Medica 51: 151–153.
• Kupchan, S.M., Britton, R.W., Ziegler, M.F. & Sigel, C.W., 1973. Bruceantin, a new potent antileukemic simaroubolide from Brucea antidysenterica. Journal of Organic Chemistry 38: 178–179.
• Lemordant, D., 1971. Contribution à l’ethnobotanique éthiopienne 2. Journal d'Agriculture Tropicale et de Botanique Appliquée 18(4–6): 142–179.
• Misawa, M., Hayashi, M. & Takayama, S., 1985. Accumulation of antineoplastic agents by plant tissue cultures. In: Neumann, K.H., Barz, W. & Reinhard, E. (Editors). Primary and secondary metabolism of plant cell cultures. Springer, Berlin. pp. 235–245.
• Murakami, C., Fukamiya, N., Tamura, S., Okano, M., Bastow, K.F., Tokuda, H., Mukainaka, T., Nishino, H. & Lee, K.-H., 2004. Multidrug-resistant cancer cell susceptibility to cytotoxic quassinoids, and cancer chemopreventive effects of quassinoids and canthin alkaloids. Bioorganic & Medicinal Chemistry 12(18): 4963–4968.
• Odojo, A., Piart, J., Polonsky, J. & Roth, M., 1981. Etude d’effet insecticide de deux quassinoides sur des larves de Locusta migratoria Ret.f. (Lorthoptera, Acrididae). Comptes Rendus Académie des Sciences (Paris) Serie C 293: 241–244.
• Okano, M., Fukamiya, N., Tagahara, K., Cosentino, M., Lee, T.T.-Y., Morris-Natschke, S. & Lee, K.-H., 1996. Anti-HIV activity of quassinoids. Bioorganic and Medicinal Chemistry Letters 6: 701–706.
• O’Neill, M.J., Bray, D.H., Boardman, P., Phillipson, J.D., Warhurst, D.C., Peters, W. & Suffness, M., 1986. Plants as sources of antimalarial drugs: in vitro antimalarial activities of some quassinoids. Antimicrobial Agents and Chemotherapy 30: 101–104.
• Simão, S.M., Barreiros, E.L., Da Silva, M.F.G.F. & Gottleib, O.R., 1991. Chemogeographical evolution of quassinoids in Simaroubaceae. Phytochemistry 30: 853–865.
• Thomas, M.C., Heppner, J.B., Woodruff, R.E., Weems, H.V., Steck, G.J. & Fasulo, T.R., 2005. Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Insecta: Diptera: Tephritidae). [Internet] Institute of Food and Agricultural Sciences, University of Florida, Florida. http://creatures.ifas.ufl.edu. Accessed May 2007.
Sources of illustration
• Wild, H. & Phipps, J.B., 1963. Simaroubaceae. In: Exell, A.W., Fernandes, A. & Wild, H. (Editors). Flora Zambesiaca. Volume 2, part 1. Crown Agents for Oversea Governments and Administrations, London, United Kingdom. pp. 210–220.
Author(s)
O.M. Grace
PROTA Country Office United Kingdom, Royal Botanic Gardens, Kew, Richmond, Surrey TW9 3AB, United Kingdom
D.G. Fowler
Flat 4 Abbotsrood, 1 Milnethorpe Road, Eastbourne BN20 7NR, Sussex, United Kingdom


Editors
G.H. Schmelzer
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
A. Gurib-Fakim
Faculty of Science, University of Mauritius, Réduit, Mauritius
Associate editors
C.H. Bosch
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
M.S.J. Simmonds
Royal Botanic Gardens, Kew, Richmond, Surrey TW9 3AB, United Kingdom
R. Arroo
Leicester School of Pharmacy, Natural Products Research, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom
A. de Ruijter
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
General editors
R.H.M.J. Lemmens
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
L.P.A. Oyen
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
Photo editor
A. de Ruijter
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands

Correct citation of this article:
Grace, O.M. & Fowler, D.G., 2008. Brucea antidysenterica J.F.Mill. In: Schmelzer, G.H. & Gurib-Fakim, A. (Editors). Prota 11(1): Medicinal plants/Plantes médicinales 1. [CD-Rom]. PROTA, Wageningen, Netherlands.
Distribution Map wild


flowering branch.
Redrawn and adapted by Iskak Syamsudin



flowering branch


flowering branch


part of male inflorescence


male flower