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

作　　者：ZHUANG Xiao-Mei CHEN Lin TAN Yan YANG Hai-Ying LU Chuang GAO Yue LI Hua 

机构地区：[1]State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing100850, China [2]Institute of Radiation Medicine, Beijing 100850, China [3]Department of DMPK, Biogen, USA

出　　处：《Chinese Journal of Natural Medicines》2017年第9期695-702,共8页中国天然药物（英文版）

基　　金：supported by Chinese National Science & Technology Major Special Project on Major New Drug Innovation(Nos.2008ZXJ09006001 and 2015ZX09J15104);National Natural Science Foundation of China(No.81130067)

摘　　要：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.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 acid Herb-drug interaction Reaction phenotyping Human liver microsomes 

分 类 号：R965[医药卫生—药理学] R969.1[医药卫生—药学]