title: Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases.
abstract: Licochalcone A (LCA) is a major bioactive compound in Licorice, a widely used herbal medicine. In this study, the inhibitory effects of LCA against human UDP-glucuronosyltransferases (UGTs) and LCA associated herb-drug interactions were systematically investigated. Our results demonstrated that LCA displayed broad-spectrum inhibition against human UGTs. LCA exhibited strong inhibitory effects against UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A9, and 2B7 (both IC50 and Ki values lower than 5 μM), while showing moderate inhibitory effects against UGT1A8, 1A10, 2B4, 2B15, and 2B17. The inhibitory effects of LCA against two major UGTs, including UGT1A1 and 1A9, were further investigated in human liver microsomes (HLMs), where the potential risks of LCA via inhibition of UGT1A1 and 1A9 were predicted by combining the in vitro inhibitory data and physiological data. The results from this study also showed that several LCA-containing products were able to increase the area under the curve (AUC) of the substrates that were predominantly metabolized by UGT1A1 or 1A9. These findings together demonstrate that LCA has a potent and broad-spectrum inhibitory effect against most human UGTs and thus suggest that much caution should be exercised when high-dose LCA is co-administered with UGT substrates.
authors.affiliation: First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Qi
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, USA.
authors.forename: James Y
authors.initials: JY
authors.lastname: Hong
authors.affiliation: First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: 13796059990@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: geguangbo@dicp.ac.cn.
authors.forename: Guang-Bo
authors.initials: GB
authors.lastname: Ge
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
mesh_terms: D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007700:Kinetics
chemical_list: D047188:Chalcones; D014453:Glucuronosyltransferase; C070840:licochalcone A
keywords: Broad-spectrum inhibitor; Herb-drug interactions (HDIs); Licochalcone A (LCA); UDP-Glucuronosyltransferases (UGT)