Fructus Bruceae consists of the dried ripe fruits of Brucea javanica (L.) Merr. (Simaroubaceae) (1, 2).
Brucea amarissima Desv. ex Gomes, B. sumatrana Roxb., Gonus amarissimus Lour., Lussa amarissima O. Ktze (2, 3).
Selected vernacular names
Biji makassar, bulah makassar, Java brucea, k'u-shen-tzu, kho sam, ko-sam, kusheng- tzu, nha dàm tùr, raat cha dat, raat dat, ratchadat, sàu dau rùng, xoan rùng, ya tan tzu, ya-dan-zi, yadãnzi (1–7).
A shrub or small tree, 1–3 m high; younger parts softly pubescent. Leaves compound-paripinnate; leaflets 5–11, oval-lanceolate, 5–10cm long by 2–4cm wide; apex acuminate, base broadly cuneate and often somewhat oblique; margin serrate; both surfaces densely pubescent, especially the underside. Flowers minute, purple, in numerous small cymes or clusters collected into axillary panicles. Sepals 4, connate at the base. Petals 4, villous, glandular at the tips. Male flowers, stamens 4, pistil reduced to a stigma; female flowers, stamens 4, much reduced. Ovary with 4 free carpels. Fruit and drupe ovoid, black when ripe. Seeds, compressed, rugose, blackish brown (3–5).
Plant material of interest: dried ripe fruit or seed
Fruit also refers to the kernel or seed with the pulp removed (3, 4).
The fruit is ovoid, 6–10mm long by 4–7mm in diameter. Externally black or brown, with raised reticulate wrinkles, the lumen irregularly polygonal, obviously ribbed at both sides. Apex acuminate, base having a dented fruit stalk scar, shell hard and brittle. Seeds ovoid, 5–6mm long by 3–5mm in diameter, externally yellowish white, reticulate; testa thin, cotyledons milky white and oily (1, 3, 4).
Odour slight; taste, very bitter (1, 4).
The pulverized pericarp is brown. Epidermal cells polygonal, with brown cellular contents; parenchymatous cells polygonal, containing clusters of calcium oxalate prisms, up to 30 mm in diameter. Stone cells subrounded or polygonal, 14–38mm in diameter (1).
Powdered plant material
Powdered seeds yellowish white. Testa cells polygonal and slightly elongated. Endosperm and cotyledon cells contain aleurone grains (1).
Indigenous to China, India, Indonesia, and Viet Nam (3, 4).
General identity tests
Macroscopic and microscopic examinations (1, 3, 4).
The test for Salmonella spp. in Fructus Bruceae products should be negative. The maximum acceptable limits of other microorganisms are as follows (8–10). For preparation of decoction: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g. Preparations (capsules) for internal use: aerobic bacteria-not more than 105/g; fungi-not more than 104/g; enterobacteria and certain Gram-negative bacteria-not more than 103/g; Escherichia coli-0/g.
Foreign organic matter
Not more than 2% (2).
Not more than 6% (2).
Not more than 0.6% (2).
Not less than 18% (2).
Dilute ethanol-soluble extractive
Not less than 26% (2).
To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin in Fructus Bruceae is not more than 0.05 mg/kg (10). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (8) and guidelines on predicting dietary intake of pesticide residues (11).
Recommended lead and cadmium levels are no more than 10.0 and 0.3mg/kg, respectively, in the final dosage form of the plant material (8).
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (8).
Other purity tests
Chemical and moisture tests to be established in accordance with national requirements.
Contains bruceosides and related quassinoids. Quantitative content requirement to be established. Quantitative determination of quassinoid triterpenes by a high-performance liquid chromatographic method developed for the determination of bruceoside A (12).
Major chemical constituents
Quassinoid triterpenes, including bruceantin, bruceantinol, bruceantinoside A, bruceins A–G and Q, brucein E 2-O-β-D-glucoside, bruceolide, bruceosides A– C, brusatol, dehydrobruceantinol, dehydrobruceins A and B, dehydrobrusatol, dihydrobrucein A, yadanzigan, yadanziolides A–D, and yadanziosides A–P predominate as the secondary metabolite constituents (13, 14). Representative quassinoid structures are presented in the figure.
Seeds for decoction, or capsules (1, 3, 4). Store in airtight container, protected from light and moisture (1).
Uses supported by clinical data
Uses described in pharmacopoeias and in traditional systems of medicine
Treatment of amoebic dysentery and malaria (1, 3, 14, 15).
Uses described in folk medicine, not supported by experimental or clinical data
As a poultice on boils, to treat ringworm, whipworm, roundworm and tapeworm, scurf, centipede bites, haemorrhoids, and enlarged spleen (3–6). The seed and seed oil have been used in the treatment of warts and corns (1, 4). Fructus Bruceae has been used in the treatment of trichomoniasis, corns and verrucae (6).
Amoebicidal and antibacterial activity
A number of in vitro studies have indicated that extracts of Brucea javanica kernels are effective amoebicides. In one such study, a crude butanol extract of B. javanica was highly active against Entamoeba histolytica (16). This amoebicidal activity was associated with two polar compounds isolated from the extract, bruceantin and brucein C, which are quassinoid constituents (16). (Brucea quassinoids were active against E. histolytica and other protozoa in vitro (17, 18).) The quassinoids were potent inhibitors of protein synthesis both in mammalian cells and in malaria parasites, and it has been suggested that this effect accounts for their amoebicidal activity (17). In one other investigation, brusatol, another quassinoid isolated from the seeds of B. javanica, was also reported to be effective in the treatment of dysentery (19). Extracts from the kernels of B. javanica have also been reported to possess antibacterial activity against Shigella shiga, S. flexneri, S. boydii, Salmonella lexington, Salmonella derby, Salmonella typhi type II, Vibrio cholerae inaba and Vibrio cholerae ogawa (20).
Numerous in vitro and in vivo studies have demonstrated the antiplasmodial activity of Fructus Bruceae extracts. In vitro studies have determined that bruceantin, a quassinoid constituent of the drug, exhibited significant antiplasmodial activity against Plasmodium falciparum (21, 22). Extracts of the drug were also active in vitro against chloroquine-resistant P. falciparum (23, 24) and in vivo against P. berghei (mice) (23, 25). Nine quassinoid constituents of the drug had in vitro IC50 values of 0.046–0.0008 mg/ml against chloroquine-resistant P. falciparum strain K-1 (23). Four of these compounds were also active in vivo against P. berghei infections in mice after oral dosing (23), and three of the compounds, bruceins A–C, had in vitro activity comparable to that of the antimalarial drug mefloquine (24). Bruceolide, another quassinoid constituent of B. javanica, was also effective in vivo (mice) against P. berghei, and was reported to be more effective than chloroquine (25). A recent in vitro screening of quassinoids against various protozoa showed that brucein D and brusatol have very selective inhibitory activity against P. falciparum (17).
Quassinoids isolated from B. javanica are reported to have cytotoxic activity in vitro (17, 26, 27). Bruceantin was tested in phase I clinical cancer trials, but no tumour regression was observed (28, 29).
Brucea javanica fruit extracts have been used clinically in the treatment of amoebic dysentery (14, 15). These investigations indicated that the antidysenteric activity of the Brucea extract was less effective than that of emetine (14, 15).
Fructus Bruceae should not be administered to children or pregnant women (6).
No information available.
Pregnancy: teratogenic and non-teratogenic effects
No data available. Preparations containing Fructus Bruceae must not be administered to pregnant women (6).
Excretion of Fructus Bruceae into breast milk and its effects on infants have not been established; therefore this drug should not be administered to nursing women.
Fructus Bruceae should not be administered to young children (6).
No information available about general precautions or precautions concerning carcinogenesis, mutagenesis, or impairment of fertility; drug interactions; or drug and laboratory test interactions.
Some cases of anaphylaxis have been reported after external applications of the fruits of B. javanica (30).
Daily dose to treat amoebiasis, 4–16g as a decoction or powder in three divided doses for 3–7 days (3); to treat malaria, 3–6g in three divided doses after meals for 4 or 5 days (3).
1. Pharmacopoeia of the People's Republic of China (English ed.). Guangzhou, Guangdong Science and Technology Press, 1992.
2. Materia medika Indonesia, Jilid I. Jakarta, Departemen Kesehatan, Republik Indonesia, 1977.
3. Medicinal plants in Viet Nam. Manila. World Health Organization Regional Office for the Western Pacific, 1990 (WHO Regional Publications, Western Pacific Series, No. 3).
4. Medicinal plants in China. Manila, World Health Organization, 1989 (WHO Regional Publications, Western Pacific Series, No. 2).
5. Keys JD. Chinese herbs, their botany, chemistry and pharmacodynamics. Rutland, VT, CE Tuttle, 1976.
6. Hsu HY. Oriental materia medica, a concise guide. Long Beach, CA, Oriental Healing Arts Institute, 1986.
7. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, August 8, 1995 production (an on-line database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network (STN) of Chemical Abstracts Services).
8. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.
9. Deutsches Arzneibuch 1996. Vol. 2. Methoden der Biologie. Stuttgart, Deutscher Apotheker Verlag, 1996.
10. European Pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1997.
11. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (unpublished document WHO/FSF/FOS/97.7; available from Food Safety, WHO, 1211 Geneva 27, Switzerland).
12. Chi H, Wang YP, Zhou TH. Determination of the anticancer drug bruceoside A in the Chinese drug, Yadanzi (Brucea javanica Merr.). Journal of chromatography, 1991, 543:250–256.
13. Polonsky J. Quassinoid bitter principles, II. In: Herz W et al., eds. Progress in the chemistry of organic natural products, Vol. 47. Berlin, Springer-Verlag, 1972.
14. Tang W, Eisenbrand G. Chinese drugs of plant origin, chemistry, pharmacology and use in traditional and modern medicine. Berlin, Springer-Verlag, 1992:207–222.
15. Steak EA. The chemotherapy of protozoan diseases, Vol. 1. Washington, DC, US Government Printing Office, 1972.
16. Keene AT et al. In vitro amoebicidal testing of natural products, Part I. Methodology. Planta medica, 1986, 52:278–285.
17. Wright CW et al. Quassinoids exhibit greater selectivity against Plasmodium falciparum than against Entamoeba histolytica, Giardia intestinalis or Toxoplasma gondii in vitro. Journal of eukaryotic microbiology, 1993, 40:244–246.
18. Wright CW et al. Use of microdilution to assess in vitro antiamoebic activities of Brucea javanica fruit, Simarouba amara stem, and a number of quassinoids. Antimicrobial agents and chemotherapy, 1988, 32:1725–1729.
19. Sato Y, Hasegawa M, Suto N. Identity of brusatol and yatansin, an antidysenteric agent. Agricultural and biological chemistry, 1980, 44:951–952.
20. Wasuwat S et al. Study on antidysentery and antidiarrheal properties of extracts of Brucea amarissima. Bangkok, Applied Science Research Center of Thailand, 1971:14 (Research Project Report 17/10, 2).
21. O'Neill MJ et al. Plants as sources of antimalarial drugs: in vitro antimalarial activities of some quassinoids. Antimicrobial agents and chemotherapy, 1986, 30:101– 104.
22. Ayudhaya T et al. Study on the in vitro antimalarial activity of some medicinal plants against Plasmodium falciparum. Bulletin of the Department of Medical Sciences (India), 1987, 9:33–38.
23. O'Neill MJ. Plants as sources of antimalarial drugs, Part 4. Activity of Brucea javanica fruits against chloroquine-resistant Plasmodium falciparum in vitro and against Plasmodium berghei in vivo. Journal of natural products, 1987, 50:41–48.
24. Pavanand K et al. In vitro antimalarial activity of Brucea javanica against multi-drug resistant Plasmodium falciparum. Planta medica, 1986, 2:108–111.
25. Ngo VT et al. Effectiveness of Brucea sumatrana plant against malaria. Duoc hoc, 1979, 4:15–17.
26. Darwish FA, Evan FJ, Phillipson JD. Cytotoxic bruceolides from Brucea javanica. Journal of pharmacy and pharmacology, 1979, 31:10.
27. Ohnishi S et al. Bruceosides D, E and F, three new cytotoxic quassinoid glycosides from Brucea javanica. Journal of natural products, 1995, 58:1032–1038.
28. Liesmann J et al. Phase I study on Bruceantin administered on a weekly schedule. Cancer treatment report, 1981, 65:883–885.
29. Bedikian AY et al. Initial clinical studies with bruceantin. Cancer treatment report, 1979, 63:1843–1847.
30. Zheng GQ et al. A report on three cases of anaphylaxis caused by external application of the fruit of Brucea javanica. Bulletin of the Chinese materia medica, 1986:11–12.