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大鼠体内曼陀罗紫花颠茄碱A、曼陀罗米林I、反式阿魏酰酪胺和大麻素F生物活性化合物的代谢产物鉴定

Metabolites Identification of Bioactive Compounds Daturataturin A, Daturametelin I, -Trans-Feruloyltyramine, and Cannabisin F From the Seeds of in Rats.

作者信息

Xu Silun, Liu Yan, Xiang Ling, Zhou Fan, Li Hongyu, Su Yongjian, Xu Xinyi, Wang Qi

机构信息

Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, China.

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Harbin, China.

出版信息

Front Pharmacol. 2018 Jul 9;9:731. doi: 10.3389/fphar.2018.00731. eCollection 2018.

Abstract

L. is a widely used traditional herbal medicine, and withanolides and amides are the two groups of main bioactive constituents in seeds. This study aimed to elucidate the metabolism of four representative bioactive compositions containing daturataturin A (), daturametelin I (), -trans-feruloyltyramine (), and cannabisin F () in rats. After separately oral administration of 20 mg/kg withanolides () and amides () to rats, a total of 12, 24, and 21 metabolites were detected in the plasma, urine, and fecal samples, respectively. Among them, three hydroxylated metabolites, , and , were detected in plasma and rat liver microsome incubation system in high abundance. Two metabolites of and were unambiguously identified by comparing with reference standards. Particularly, the methylated metabolite 27α-methoxy-(22R)-22,26-epoxy-27-[(β-D-glucopyranosyl)oxy]ergosta-2,4,6,24-tetraene-1,26-dione (daturametelin L) is a new compound. The withanolides could readily get hydroxylation or methylation metabolism. Meanwhile, the phase II metabolism (glucuronidation or sulfation) was the major reaction for the amides. This is the first study on metabolism of these active compounds in seeds of .

摘要

L.是一种广泛使用的传统草药,而睡茄内酯和酰胺是其种子中的两类主要生物活性成分。本研究旨在阐明四种代表性生物活性成分,即含颠茄他图林A()、颠茄美替林I()、反式阿魏酰酪胺()和大麻素F()在大鼠体内的代谢情况。分别以20mg/kg的剂量给大鼠口服睡茄内酯()和酰胺()后,在血浆、尿液和粪便样本中分别检测到了总共12种、24种和21种代谢产物。其中,三种羟基化代谢产物,即 、 和 ,在血浆和大鼠肝微粒体孵育体系中被高丰度检测到。通过与参考标准品比较,明确鉴定出了 和 的两种代谢产物。特别地,甲基化代谢产物27α-甲氧基-(22R)-22,26-环氧-27-[(β-D-吡喃葡萄糖基)氧基]麦角甾-2,4,6,24-四烯-1,26-二酮(颠茄美替林L)是一种新化合物。睡茄内酯很容易发生羟基化或甲基化代谢。同时,II相代谢(葡萄糖醛酸化或硫酸化)是酰胺的主要反应。这是关于这些活性化合物在种子中代谢的首次研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9db7/6052896/3da0df2c709d/fphar-09-00731-g001.jpg

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