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藜芦胺和12β-羟基藜芦酰棋盘花碱在小鼠体外肝代谢研究 被引量:1

Study on Metabolism of Veratramine and 12β-Hydroxylveratroylzygadenine in Rat Liver Microsomes
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摘要 采用LC-MS/MS方法对小鼠肝微粒体中藜芦胺(veratramine,VAM)和12β-羟基藜芦酰棋盘花碱(12β-hydroxylveratroylzyga-denine,VOG)的代谢产物进行分析,结合体内VAM和VOG及其代谢物的分析结果,推测VAM和VOG在小鼠体外肝代谢规律.结果显示,VAM在小鼠肝微粒体孵化体系中检测到7个代谢产物,其代谢途径为羟基化、磺酸化、甲基化,其中甲基化是VAM I相代谢的主要代谢途径.VOG在小鼠肝微粒体孵化体系中检测到7个代谢产物,其代谢途径为酯键水解、脱氢、酯键水解加脱氢、羟基化、酯键水解加乙酰化,其中酯键水解是其I相代谢的主要代谢途径.以上结果表明,VAM和VOG在小鼠肝微粒体孵化体系中主要进行I相代谢反应,VAM和VOG的主要代谢产物分别为甲基化代谢产物和酯键水解产物. To establish the metabolic profile of veratramine(VAM)and 12β-hydroxylveratroylzygadenine(VOG)in mouse liver microsome, LC-MS/MS was used to analyze VAM and VOG and its metabolites in mouse liver microsome, and to speculate its metabolic regulation. The results show that there are 7 metabolites of VAM tentatively identified in incubation system ofmouse liver microsome. The metabolic pathways of VAM in mouse liver microsome are proposed as hydrolysis, hydroxylation, sulfonation, and methylation. Methylation is the major metabolic pathways of VAM phase 1. 7 metabolites of VOG were tentatively identified in incubation system of mouse liver microsome. The metabolic pathways of VOG in mouse liver microsome are proposed as hydrolysis of ester bond, dehydrogenation, and hydrolysis of ester bond plus dehydrogenation, hydroxylation, and hydrolysis of ester bond plus acetylation. Hydrolysis of ester bond is the major metabolic pathways of VOG phase I. It is concluded that metabolites of VAM and VOG mainly belong to phase I metabolic reactions in incubation system of mouse liver microsome. The main metabolites of VAM and VOG were methylation and hydrolysis of ester bond, respectively.
作者 刘习平 武彦彤 唐蕾 范玉洁 丛悦 LIU Xiping;WU Yantong;TANG Lei;FAN Yujie;CONG Yue(Institute of Pharmacy, Henan University, Henan Kaifeng 475004, Chin)
出处 《河南大学学报(自然科学版)》 CAS 2018年第2期179-187,共9页 Journal of Henan University:Natural Science
基金 河南大学科研项目(xxjc20140018)
关键词 藜芦胺 12β-羟基藜芦酰棋盘花碱 小鼠肝微粒体 体外代谢 veratramine 12β-hydroxylveratroylzygadenine mouse liver microsome in vitro metabolism
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