Development of new drugs based on the metabolic activation by intestinal bacteria.

1. 芍药代谢物衍生物的合成及其抗惊厥活性通过芍药根中芍药苷与人肠道短乳杆菌在巯基化合物存在下的孵育，制备了17种不同的芍药代谢物衍生物，并对其抗惊厥活性进行了研究；8-（正己基硫）-、8-环戊基硫-、8-（对己基硫）-和8-苯甲酰硫代代谢素表现出较强的活性。最后一个化合物经柱层析分离后，7s -衍生物的抗惊厥活性最强，而7r -衍生物的肌肉松弛作用最强。肠道细菌代谢产物人参皂苷对肿瘤细胞转移和凋亡的影响代谢产物(20S)-原人参二醇20- o -糖苷人参皂苷Rb1在小鼠中显示出有效的抗转移作用。关于其抗转移作用的机制，证实该代谢物通过调节细胞周期蛋白D、p27 kip、c-myc等凋亡相关蛋白诱导肿瘤细胞凋亡3。肠道细菌介导的新反应研究进展。大黄素转化为大黄素蒽醌。Demethylationc。在上述项目的调查中，我们从人类粪便中分离出拟杆菌、胃链球菌和真杆菌三株，催化了新的反应a-c。

1. Synthesis of paeonimetabolin derivatives and their anti-convulsant activityBy incubation of paeoniflorin from peony roots with a human intestinal bacterium Lactobacillus brevis in the presence of mercapto compounds, 17 different kinds of paeonimetabolin derivatives were prepared and examined their anti-convulsant activity ; 8-(n-hexylthio)-, 8-cyclopentylthio-, 8-(p-tolylthio)-, and 8-benzoylthiopaeonimetabolin showed potent activity. After separation of the last compound by column chromatography, 7S-derivative showed the most potent anti-convulsant activity, but 7R-derivative showed the muscle relaxation effect.2. Effects of a metabolite of ginsenoside by intestinal bacteria on metastasis and apoptosis of tumor cellsA metabolite (20S)-protopanaxadiol 20-O-glucoside of ginsenoside Rb1 showed potent anti-metastatic action in mice. As to the mechanism of the anti-metastatic action, it was demonstrated that this metabolite induced apoptosis of the tumor cells by modulating apoptosis related proteins such as cyclin D, p27 kip and c-myc etc.3. Development of new reactions mediated by intestinal bacteria.a. Conversion of rhein to rhein anthroneb. Demethylationc. DehydroxylationDuring the investigation under the above project, we islated three bacterial strains Bacteroides sp., Peptostreptococcus sp., and Eubacterium sp., from human feces, which catalyzed the new reactions a-c.