Metabolic map of osthole and its effect on lipids
| Autor: | Hong-Ning Liu, Fei Li, Qi Zhao, Xin-Mei Li, Frank J. Gonzalez |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Spectrometry Mass Electrospray Ionization Health Toxicology and Mutagenesis Administration Oral Peroxisome proliferator-activated receptor Hydroxylation Toxicology Methylation Biochemistry Article Mice 03 medical and health sciences Metabolomics Coumarins In vivo Animals Pharmacology chemistry.chemical_classification Molecular Structure CYP3A4 Lysophosphatidylcholines Biological activity General Medicine Metabolism Lipids Metabolic pathway 030104 developmental biology Enzyme chemistry Inactivation Metabolic Peritoneal Absorption Microsomes Liver Hydrogenation Lysophospholipids Chromatography Liquid |
| Zdroj: | Xenobiotica. 48:285-299 |
| ISSN: | 1366-5928 0049-8254 |
| DOI: | 10.1080/00498254.2017.1306660 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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