| Abstract: | In the present study, we aimed to ascertain the metabolic detoxification routes of genipin via CYP3A4, SULT2A1, and UGT1A1 in HepaRG cells. It was found that the hepatic CYP3A4, SULT2A1, and UGT1A1 synergistically mediated the metabolic detoxification of genipin, and the CYP3A4 was the limited enzyme. In detail, the pivotal detoxification pathway was CYP3A4-SULT2A1/UGT1A1, indicating that SULT2A1 and UGT1A1 further catalyzed the phase II detoxification metabolism followed by the genipin metabolization by CYP3A4 to the phase I metabolites with alleviated toxicity. Our findings provided valuable cues for future studies on the detoxification of genipin, even the compatibility detoxification of Zhi-zi. Moreover, these data facilitated the development and rational administration of genipin and Zhi-zi. |
