Ergosterol peroxide (EPO, 1) is a major antitumor sterol produced by edible or medicinal mushrooms. Following oral administration of 1 to rats or anaerobic in vitro incubation of 1 with rat fecal bacteria, three metabolites were detected and their structures were identified to be 5a a,6a a-epoxyergosta-8(14),22-diene-3b b,7a a-diol (M1, 2), 5a a,6a a-epoxyergosta-8,22-diene-3b b,7a a-diol (M2, 3), and 5a a,6a a-epoxy-3b b-hydroxyergosta-22-ene-7-one (M3, 4) by spectroscopic analysis. Of these, M2 and M3 showed more potent inhibitory activity than the original compound 1 against proliferation of CACO-2, WiDr, DLD-1 and Colo320 human colorectal adenocarcinoma cells. These findings suggest that bacterial metabolites of EPO play a significant role in its cytotoxic activity against human colorectal cancer cells.Key words ergosterol peroxide; rat intestinal bacteria; cytotoxic activity Biol. Pharm. Bull. 31(5) 949-954 (2008)
A neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to induce parkinsonism in rodents and human via dopaminergic cell death by a common oxidative mechanism. To find whether a neurotoxin-induced neurotoxicity is prevented by the treatment with an antioxidant, we investigated the effects of ginsenoside Rb 1 , a major saponin from Panax ginseng, on lipid peroxidaton and neurotoxicity induced by MPTP in mice using chemiluminescense-HPLC. Levels of lipid hydroperoxides in plasma and liver were increased by MPTP treatment, but the increased levels of this were not observed in mice pretreated with ginsenoside Rb 1 . Activities of protein kinase C and NADPH-cytochrome c reductase in the pretreated group with ginsenoside Rb 1 were lower than in MPTP groups. Treatment with ginsenoside Rb 1 was, however, less effective in suppressing the influence of MPTP on the levels of dopamine and its metabolite, homovanillic acid in the striatum of mice brain. These results indicate that ginsenoside Rb 1 has an antioxidant effect and may not have the ability enough to suppress the neurotoxicity induced by MPTP.
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