期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 50, 期 6, 页码 2074-2083出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2012.03.048
关键词
S-equol; Metabolism; Hepatocytes; Metabolite identification
资金
- Ausio Pharmaceuticals, LLC
S-equol is a selective estrogen receptor beta (ER beta) agonist which is produced in certain individuals after ingestion of its precursor daidzein, an isoflavone present in soy. S-equol is thought to provide certain health benefits, including reduced menopausal symptoms. The metabolic profile of S-equol was determined in vivo in Sprague-Dawley rats and cynomolgus monkeys, and in vitro using hepatocytes from rat, monkey, and human. High resolution MS fragmentation patterns indicated that the major metabolite of S-equol in rat plasma and urine was the 4'-glucuronide conjugate, with lesser amounts of unconjugated S-equol, the 7-sulfate conjugate, and the 4'-glucuronide-7-sulfate diconjugate. Monkeys also showed extensive metabolism, with the major species in plasma being the 4'-glucuronide and the 7-sulfate-4'-glucuronide diconjugate; urine contained primarily the 4'-glucuronide, as seen in the rat. In vitro metabolism by hepatocytes was extensive and similar in all species, with fragmentation patterns also indicating that the 4'-glucuronide was the major metabolite. No oxidative metabolites of [C-14] S-equol were detected in either in vivo or in vitro studies. These findings show that glucuronidation is the primary pathway for the metabolism of S-equol in rat, monkey and man, and that all metabolic routes of S-equol observed in vitro were also observed in vivo. (C) 2012 Elsevier Ltd. All rights reserved.
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