title: Isochlorogenic acid A affects P450 and UGT enzymes in vitro and in vivo.
abstract: Isochlorogenic acid A (ICQA), which has anti-inflammatory, hepatoprotective, and antiviral properties, is commonly presented in fruits, vegetables, coffee, plant-based food products, and herbal medicines. These herbal medicines are usually used in combination with other medicines in the clinic. However, little is known about the regulatory effects of ICQA on drug-metabolizing enzymes and the herb-drug interactions. In the present study, we evaluated the inhibitory potentials of ICQA on CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2D6, and CYP2E1 in vitro based on a cocktail approach. The P450 and UGT activities in mice treated with ICQA for a prolonged period were also determined. Our results demonstrated that ICQA exhibited a weak inhibitory effect on CYP2C9 in human liver microsomes with IC50being 57.25 μmol·L-1and Ki being 26.77 μmol·L-1. In addition, ICQA inhibited UGT1A6 activity by 25%, in the mice treated with ICQA (i.p.) at 30 mg·kg-1for 14 d, compared with the control group. Moreover, ICQA showed no mechanism-based inhibition on CYP2C9 or UGT1A6. In conclusion, our results further confirm a safe use of ICQA in clinical practice.
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: hhp_770505@hotmail.com.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Hao
mesh_terms: D000818:Animals; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000737:chemistry / Q000201:enzymology
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; C469310:isochlorogenic acid; D002726:Chlorogenic Acid; D003577:Cytochrome P-450 Enzyme System; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase
keywords: Herb-drug interaction; Isochlorogenic acid A; P450; UGT