哈巴苷在大鼠体内代谢产物的鉴定与分析
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篇名: 哈巴苷在大鼠体内代谢产物的鉴定与分析
TITLE:
摘要: 目的:研究玄参活性成分哈巴苷在大鼠体内的代谢产物及其分布、代谢类型和其可能的活性。方法:4只SD大鼠随机分为空白组(超纯水)和给药组(哈巴苷对照品溶液),每组2只,ig给药,160 mg/kg,每日2次,连用3 d。于给药前及首次给药后每12 h收集各组大鼠尿液和粪便,最后1次给药后0.5、1 h穿心取血8 mL并取出心、肝、脾、肺、肾、胃和小肠等组织,分别制备血液、尿液、粪便及各组织样品溶液。采用高效液相色谱-质谱联用法检测和鉴定哈巴苷在大鼠体内的代谢产物并推测其代谢途径,采用Pharm Mapper软件预测代谢产物活性。结果:从大鼠体内鉴定出哈巴苷代谢产物12种,其原型及代谢产物主要分布在心、肝、脾、肺、肾、胃和小肠中,其代谢类型主要包括水解、脱水、还原、甲基化、硫酸酯化、葡萄糖醛酸结合、一级香豆酸结合等。12种化合物可能具有治疗癫痫、肌萎缩侧索硬化、糖尿病、脑中风等活性。结论:哈巴苷可能是以原型和代谢产物的形式发挥药效的。本研究为归属玄参体内代谢产物来源、研究玄参显效形式、阐明玄参药理作用机制和炮制机制提供了依据。
ABSTRACT: OBJECTIVE: To study the metabolites, distribution, metabolic type and the possible activity of harpagide which is the active component from Scrophularia ningpoensis in rats in vivo. METHODS: 4 SD rats were divided into blank group (ultra-pure water) and administration group (harpagide reference solution), 2 in each group, ig, 160 mg/kg, twice a day, for 3 d. Urine and feces were collected every 12 h before administration and the first administration; sample blood 8 mL was taken after 0.5, 1 h of last administration; heart, liver, spleen, lung, kidney, stomach and small intestine were taken. The blood, urine, feces and other tissue solutions were prepared, HPLC-MS was conducted to detect and identify the harpagide metabolites in rats in vivo and presume metabolic pathways, and PharmMapper software was used to predict metabolites activity. RESULTS: 12 harpagide metabolites were identified in rats in vivo, the form of prototypes and metabolites were distributed in heart, liver, spleen, lung, kidney, stomach and small intestine. The metabolic type mainly included hydrolysis, dehydration, reduction, methylation, sulfation, glucuronic acid binding, grade A coumaric acid binding, etc. The 12 compounds may have activities in the treatment of epilepsy, amyotrophic lateral sclerosis, diabetes, stroke, etc. CONCLUSIONS: Harpagide may be effective in the form of prototypes and metabolites. The study has provided basis for attributing the origins of metabolite, studying the effective form of S. ningpoensis clarifying its pharmacological mechanism and processing mechanism.
期刊: 2017年第28卷第10期
作者: 刘震,徐风,王静哲,刘广学,尚明英,蔡少青
AUTHORS: LIU Zhen,XU Feng,WANG Jingzhe,LIU Guangxue,SHANG Mingying,CAI Shaoqing
关键字: 玄参;哈巴苷;液质联用;代谢产物;代谢途径;活性
KEYWORDS: Scrophularia ningpoensis; Harpagide; LC-MS; Metabolite; Metabolic pathway; Activity
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