title: Metabolic map of osthole and its effect on lipids.
abstract: 1. Osthole, a coumarin compound from plants, is a promising agent for the treatment of metabolic diseases, including hyperglycemia, fatty liver, and cancers. Studies indicate that the peroxisome proliferator-activated receptors (PPAR) α and γ are involved in the pharmacological effects of osthole. The in vitro and in vivo metabolism of osthole and its biological activity are not completely understood. 2. In this study, ultra-performance chromatography electrospray ionization quadrupole time-of-ﬂight mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics was used to determine the metabolic pathway of osthole and its influence on the levels of endogenous metabolites. Forty-one osthole metabolites, including 23 novel metabolites, were identified and structurally elucidated from its metabolism in vitro and in vivo. Recombinant cytochrome P450s (CYPs) screening showed that CYP3A4 and CYP3A5 were the primary enzymes contributing to osthole metabolism. 3. More importantly, osthole was able to decrease the levels of lysophosphatidylethanolamine (LPE) and lysophosphatidylcholine (LPC) in the plasma, which explains in part its modulatory effects on metabolic diseases. 4. This study gives the insights about the metabolic pathways of osthole in vivo, including hydroxylation, glucuronidation, and sulfation. Furthermore, the levels of the lipids regulated by osthole indicated its potential effects on adipogenesis. These data contribute to the understanding of the disposition and pharmacological activity of osthole in vivo.
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming , China.|b Yunnan Key Laboratory of Natural Medicinal Chemistry , Kunming , China.|c University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming , China.|b Yunnan Key Laboratory of Natural Medicinal Chemistry , Kunming , China.
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Li
authors.affiliation: d Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine , Nanchang , China , and.
authors.forename: Hong-Ning
authors.initials: HN
authors.lastname: Liu
authors.affiliation: e Laboratory of Metabolism , Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming , China.|b Yunnan Key Laboratory of Natural Medicinal Chemistry , Kunming , China.|d Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine , Nanchang , China , and.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D006865:Hydrogenation; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D008055:Lipids / Q000097:blood*; D008244:Lysophosphatidylcholines / Q000097:blood; D008246:Lysophospholipids / Q000097:blood; D008297:Male; D055432:Metabolomics / Q000379:methods; D008745:Methylation; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D065629:Peritoneal Absorption; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D003374:Coumarins; D008055:Lipids; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; C008301:lysophosphatidylethanolamine; C046627:osthol
keywords: Lipid; metabolic disease; metabolomics; osthole; time-of-flight mass spectrometry; ultra-performance liquid chromatography