Alternative Medicine Research Today is a free monthly online journal that collates and summarizes the latest research about Alternative Medicine, including details on complementary medicine, alternative therapies, homeopathy. | ||||||||
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Evaluation of cytotoxic, genotoxic and CYP450 enzymatic competition effects of Tanzanian plant extracts traditionally used for treatment of fungal infections.van den Bout-van den Beukel CJ, Hamza OJ, Moshi MJ, Matee MI, Mikx F, Burger DM, Koopmans PP, Verweij PE, Schoonen WG, van der Ven AJ Department of General Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. c.vandenbeukel@aig.umcn.nl HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions. Published 16 May 2008 in Basic Clin Pharmacol Toxicol, 102(6): 515-26.
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