Role of metabolism by human intestinal microflora in geniposide-induced toxicity in HepG2 cells

Archives of Pharmacal Research
Mi Jeong KangTae Cheon Jeong

Abstract

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.

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Citations

Mar 20, 2015·Drug Delivery and Translational Research·Rajkumar MalayandiDeepika Aggarwal
Jun 14, 2015·AAPS PharmSciTech·Seth AmidonVivek S Dave
Nov 21, 2012·Molecular Nutrition & Food Research·Hye Gwang JeongTae Cheon Jeong
Mar 16, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Keumhan NohTae Cheon Jeong
Apr 11, 2019·Metabolites·Mahesh Raj NepalTae Cheon Jeong
Nov 2, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chunnan LiJiaming Sun
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wuwen FengCheng Peng
Dec 15, 2020·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Zhong-Shang XiaJia-Gang Deng
Apr 16, 2021·Medicinal Research Reviews·Yusha Luo, Tingting Zhou
Jun 26, 2021·World Journal of Gastroenterology : WJG·Yang WenYan-Qing Ma
Sep 27, 2014·Journal of Agricultural and Food Chemistry·Ming Ji JinHye Hyun Yoo
Aug 17, 2021·Frontiers in Physiology·Nyasha Charity MukonowenzouKennedy Honey Erlwanger

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