Intestine vs. Liver Uncovering the Hidden major Metabolic organs of Silybin in Rats.

IF 4.4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Drug Metabolism and Disposition Pub Date : 2024-10-17 DOI:10.1124/dmd.124.001817
Yuanbo Sun, Like Xie, Jing Zhang, Runing Liu, Hanbing Li, Yanquan Yang, Yapeng Wu, Ying Peng, Guangji Wang, Natalie Medlicott, Jianguo Sun
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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.

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水飞蓟宾在大鼠体内隐藏的主要代谢器官。
从奶蓟草中提取的水飞蓟宾是一种具有保肝作用的黄酮木脂素化合物。现在,水飞蓟宾已被广泛应用于膳食补充剂、功能性食品和营养保健品中。然而,迄今为止,水飞蓟宾在生物体内的代谢尚未得到系统研究。因此,我们建立了一种新型的 HPLC-Q-TOF/MS 方法来分析和鉴定水飞蓟宾在大鼠体内的原型和代谢物。结果发现,在 32 种新的代谢途径和 59 种未报道的代谢产物中,我们发现了 29 种(共 32 种)。此外,我们还发现肝脏对水飞蓟宾的首过效应高达 63.30%{正负}13.01,且只检测到一种代谢产物。而在胃肠道中发现的代谢物占全部代谢物的 88%(59 种中的 52 种)。同时,水飞蓟宾在肝脏中的高浓度也表明,大量水飞蓟宾可能积聚在肝脏中而没有被代谢掉。这些结果表明,水飞蓟宾在大鼠体内的主要代谢器官是肠道而不是肝脏,这也为探索更多有前景的水飞蓟宾保健品提供了坚实的化学基础。意义 本研究证实水飞蓟宾在大鼠体内的主要代谢器官是胃肠道而不是肝脏,而且肠道微生物与水飞蓟宾的代谢密切相关。研究首次发现了水飞蓟宾在大鼠体内的 32 条代谢途径中的 29 条,以及 59 种代谢物中的 56 种。为了进一步研究水飞蓟宾在肝脏的处置,还首次测定了水飞蓟宾在肝脏的首过效应。
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来源期刊
CiteScore
6.50
自引率
12.80%
发文量
128
审稿时长
3 months
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.
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