何首乌水提物给药后大鼠体内成分研究

doi:10.19803/j.1672-8629.2022.06.08

摘要/Abstract

摘要： 目的考察连续42 d灌胃何首乌水提物（PMW）后大鼠肝、肾、血浆和胆汁中的成分累积特征,为何首乌肝毒性研究提供数据支撑。方法采用UPLC-LTQ-Orbitrap MS技术,通过与对照品比对及通过scitific library模块分析,对大鼠不同组织中何首乌原型成分及代谢产物进行定性鉴别和推测。结果大鼠经过长期灌胃（PMW）诱导后,体内可检测到24个何首乌相关化合物,其中7个为原型成分,5个为Ⅰ相代谢产物,12个为Ⅱ相代谢产物。主要成分为二苯乙烯苷和蒽醌类原型及其代谢物。各类成分具有选择蓄积性,肾脏中蓄积成分最多,肝脏和胆汁中相当,血浆中最少。二苯乙烯苷以硫酸化和葡萄糖醛酸化反应为主,大黄素多发生氧化反应和葡萄糖醛酸化反应。结论原型成分大黄素、芦荟大黄素、大黄素-8-O-葡萄糖苷、二苯乙烯苷、大黄酸、没食子酸很可能与何首乌引发的不良反应相关,应引起关注;大黄素-葡萄糖醛酸化物和二苯乙烯苷-葡萄糖醛酸化物-硫酸化物仅在胆汁中检出,没食子酸及原儿茶酸以及大量大黄素Ⅱ相代谢物仅在肾脏中检出,这类成分的潜在毒性风险应进一步研究。

关键词: 何首乌, 何首乌水提物, 大鼠, 灌胃, 组织分布, 代谢产物, 安全评价

Abstract: Objective To investigate the accumulation characteristics of the components in the liver, kidney, plasma and bile of rats after gavage of the aqueous extract of Polygonum multiflorum for 42 consecutive days, so as to provide data support for the study on the hepatotoxicity of Polygonum multiflorum. Methods UPLC-LTQ-Orbitrap MS technology was applied to qualitatively identify and speculate the prototype components and metabolites of Polygonum multiflorum in different tissues of rats by comparing with the reference substance and analyzing using the scitific library module. Results After a long-term induction with the aqueous extract of Polygonum multiflorum by oral gavage in the rat, tweenty-four related compounds of Polygonum multiflorum could be identified and detected in vivo, of which 7 were prototype components, 5 were phase Ⅰ metabolites, and 12 were phase Ⅱ metabolites. Among which, the main components included stilbene glycosides and anthraquinone prototypes and their metabolites. Various components had a selective accumulation pattern, and the most of them accumulated in the kidney, the contents in the liver and bile were equivalent, and the least was found in the plasma. Stilbene glycosides were mainly subjected to sulfation and glucuronidation reactions, while emodin mostly undergoes oxidation reactions and glucuronidation reactions. Conclusion The prototype components emodin, aloe-emodin, emodin-8-O-glucoside, stilbene glycosides, rhein, and gallic acid are likely to be highly related to the adverse reactions caused by Polygonum multiflorum, which should attract attention. Acid and stilbene glycoside-glucuronide-sulfate are only detected in bile, gallic acid and protocatechuic acid and a large number of emodin phase II metabolites are only detected in kidney, while other potential toxicity risks should be further investigated.

Key words: Polygonum multiflorum, aqueous extract of polygonum multiflorum, rats, gavage, tissue distribution, metabolites, safety evaluation

中图分类号:

R961
R962

汪祺, 文海若, 杨建波, 王莹, 李妍怡, 马双成, 张玉杰. 何首乌水提物给药后大鼠体内成分研究[J]. 中国药物警戒, 2022, 19(6): 620-625.

WANG Qi, WEN Hairuo, YANG Jianbo, WANG Ying, LI Yanyi, MA Shuangcheng, ZHANG Yujie. Study on the components of Polygonum multiflorum aqueous extract in rats after long-term administration[J]. Chinese Journal of Pharmacovigilance, 2022, 19(6): 620-625.

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