title: Identification of urine tauro-β-muricholic acid as a promising biomarker in Polygoni Multiflori Radix-induced hepatotoxicity by targeted metabolomics of bile acids.
abstract: Polygoni Multiflori Radix (PMR) has been widely used as a tonic for centuries. However, hepatotoxicity cases linked to PMR have been frequently reported and appropriate biomarkers for clinical diagnosis are currently lacking. Here, an approach using UPLC-QqQ/MS-based targeted metabolomics of bile acids (BAs) complemented with biochemistry and histopathology was applied to characterize the development and recovery processes of PMR-induced hepatotoxicity in rats and to identify biomarkers. The expression of bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) were evaluated to investigate the underlying mechanism. Steatosis and inflammatory cell infiltration were observed in PMR-treated rats, which were accompanied by the elevation of serum biochemistry. The metabolic profiles of BAs were analyzed by Principal Component Analysis, hyodeoxycholic acid (HDCA) in serum and tauro-β-muricholic acid (TβMCA) in urine were identified as potential biomarkers for PMR-induced hepatotoxicity. The elevated expression of Bsep and decreased expression of Ntcp in the liver of PMRtreated rats indicated that hepatotoxicity was related to the disorders of BAs metabolism. Our study demonstrated that BAs may be used for clinical diagnosis of PMR-induced hepatotoxicity. Urine TβMCA was identified as a promising biomarker to facilitate the clinical monitoring of PMR-induced hepatotoxicity and may serve as potential therapeutic target.
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Li-Long
authors.initials: LL
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Ya-Xi
authors.initials: YX
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Lei-Chi
authors.initials: LC
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China. Electronic address: liping2004@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing, 210009, China. Electronic address: cpuli@163.com.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Li
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D015415:Biomarkers; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D000068676:Fallopia multiflora / Q000737:chemistry*; D008297:Male; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; C037351:tauromuricholic acid; D013656:Taurocholic Acid
keywords: Bile acids; Biomarkers; Hepatotoxicity; Polygoni multiflori radix; Targeted metabolomics