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Possible role of metabolism by the intestinal bacteria in geniposide-induced cytotoxicity was investigated in human hepatoma HepG2 cells. Initially, toxic effects of geniposide and its metabolite genipin were compared. Genipin, a deglycosylated form of geniposide, was cytotoxic at the concentrations that geniposide was not. As metabolic activation systems for geniposide, human intestinal bacterial cultures, fecal preparation (fecalase) and intestinal microbial enzyme mix were employed in the present study. When geniposide was incubated with human intestinal bacteria, either Bifidobacterium longum HY8001 or Bacteroides fragilis, for 24 h, the cultured media caused cytotoxicity in HepG2 cells. Fecalase and intestinal enzyme mix were also effective to metabolically activate geniposide to its cytotoxic metabolite. The present results indicated that genipin, a metabolite of geniposide, might be more toxic than geniposide, and that intestinal bacteria might have a role in biotransformation of geniposide to its toxic metabolite. In addition, among three activation systems tested, intestinal microbial enzyme mix would be convenient to use in detecting toxicants requiring metabolic activation by intestinal bacteria.


Mi Jeong Kang, Tilak Khanal, Hyung Gyun Kim, Dae Hun Lee, Hee Kyung Yeo, Yong Sup Lee, Young Tae Ahn, Dong Hyun Kim, Hye Gwang Jeong, Tae Cheon Jeong. Role of metabolism by human intestinal microflora in geniposide-induced toxicity in HepG2 cells. Archives of pharmacal research. 2012 Mar;35(4):733-8

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PMID: 22553067

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