{"title":"<b>Intestine vs. Liver</b> <b>?</b> <b>Uncovering the Hidden major Metabolic organs of Silybin in Rats</b>.","authors":"Yuanbo Sun, Like Xie, Jing Zhang, Runing Liu, Hanbing Li, Yanquan Yang, Yapeng Wu, Ying Peng, Guangji Wang, Natalie Medlicott, Jianguo Sun","doi":"10.1124/dmd.124.001817","DOIUrl":null,"url":null,"abstract":"<p><p>Silybin, extracted milk thistle, was a flavonolignan compound with hepatoprotective effect. Now it is commonly used in dietary supplements, functional foods, and nutraceuticals. However, the metabolism of silybin has not been systematically characterized in organisms to date. Therefore, we established a novel HPLC-Q-TOF/MS method to analyze and identify the prototype and metabolites of silybin in rats. Totally, 29 (out of 32) new metabolic pathways and 56 (out of 59) unreported metabolite products were detected. Moreover, we found that the liver had a high first-pass effect of 63.30%{plus minus}13.01 for silybin and only one metabolite was detected. And the metabolites identified in gastrointestinal tract possessed 88% of all (52 out of 59). At the same time, the high concentration of silybin in the livers also indicated large amounts of silybin may be accumulated in liver instead of being metabolized. These results indicated the primary metabolizing organ of silybin in rats was intestine rather than liver, which would also offer solid chemical foundation for exploring more promising health care products of silybin. <b>Significance Statement</b> This study confirmed the main metabolism place of silybin in rats were gastrointestinal tracts instead of livers and the intestinal microbes were closely involved. Then 29 (out of 32) metabolism pathways and 56 (out of 59) metabolites were identified for the first time in rats. And to further study the liver disposition of silybin, its hepatic first-pass effect was determined for the first time.</p>","PeriodicalId":11309,"journal":{"name":"Drug Metabolism and Disposition","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Metabolism and Disposition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1124/dmd.124.001817","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Silybin, extracted milk thistle, was a flavonolignan compound with hepatoprotective effect. Now it is commonly used in dietary supplements, functional foods, and nutraceuticals. However, the metabolism of silybin has not been systematically characterized in organisms to date. Therefore, we established a novel HPLC-Q-TOF/MS method to analyze and identify the prototype and metabolites of silybin in rats. Totally, 29 (out of 32) new metabolic pathways and 56 (out of 59) unreported metabolite products were detected. Moreover, we found that the liver had a high first-pass effect of 63.30%{plus minus}13.01 for silybin and only one metabolite was detected. And the metabolites identified in gastrointestinal tract possessed 88% of all (52 out of 59). At the same time, the high concentration of silybin in the livers also indicated large amounts of silybin may be accumulated in liver instead of being metabolized. These results indicated the primary metabolizing organ of silybin in rats was intestine rather than liver, which would also offer solid chemical foundation for exploring more promising health care products of silybin. Significance Statement This study confirmed the main metabolism place of silybin in rats were gastrointestinal tracts instead of livers and the intestinal microbes were closely involved. Then 29 (out of 32) metabolism pathways and 56 (out of 59) metabolites were identified for the first time in rats. And to further study the liver disposition of silybin, its hepatic first-pass effect was determined for the first time.
期刊介绍:
An important reference for all pharmacology and toxicology departments, DMD is also a valuable resource for medicinal chemists involved in drug design and biochemists with an interest in drug metabolism, expression of drug metabolizing enzymes, and regulation of drug metabolizing enzyme gene expression. Articles provide experimental results from in vitro and in vivo systems that bring you significant and original information on metabolism and disposition of endogenous and exogenous compounds, including pharmacologic agents and environmental chemicals.