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Identification of human cytochrome P450 and UGT enzymes involved in the metabolism of ferulic acid, a major bioactive component in traditional Chinese medicines

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Chinese Journal of Natural Medicines 2017年第9期15卷 695-702页

作者： ZHUANG Xiao-Mei CHEN Lin TAN Yan YANG Hai-Ying LU Chuang GAO Yue LI Hua State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology Beijing100850 China Institute of Radiation Medicine Beijing 100850 China Department of DMPK Biogen USA

Ferulic acid(FA) is an active component of herbal medicines. One of the best documented activities of FA is its antioxidant property. Moreover, FA exerts antiallergic, anti-inflammatory, and hepatoprotective effects. However, the metabolic pathways of FA in humans remain unclear. To identify whether human CYP or UGT enzymes are involved in the metabolism of FA, reaction phenotyping of FA was conducted using major CYP-selective chemical inhibitors together with individual CYP and UGT Supersomes. The CYPand/or UGT-mediated metabolism kinetics were examined simultaneously or individually. Relative activity factor and total normalized rate approaches were used to assess the relative contributions of each major human CYPs towards the FA metabolism. Incubations of FA with human liver microsomes(HLM) displayed NADPH-and UDPGA-dependent metabolism with multiple CYP and UGT isoforms involved. CYPs and UGTs contributed equally to the metabolism of FA in HLM. Although CYP1 A2 and CYP3 A4 appeared to be the major contributors in the CYP-mediated clearance, their contributions to the overall clearance are still minor(< 25%). As a constitute of many food and herbs, FA poses low drug-drug interaction risk when co-administrated with other herbs or conventional medicines because multiple phase I and phase II enzymes are involved in its metabolism.

关键词： Ferulic 酸植物药相互作用反应 phenotyping 人的肝微体

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