中国药物警戒 ›› 2024, Vol. 21 ›› Issue (12): 1377-1381.
DOI: 10.19803/j.1672-8629.20240427

• 何首乌质量及安全性评价专栏（三） • 上一篇    下一篇

基于物质基础结合HepaRG细胞实验探究何首乌肝损伤成分

李妍怡1, 文海若2△, 杨颜榕3, 马双成4,5#, 汪祺6,*   

  1. 1北京中医药大学中药学院,北京 102400;
    2中国食品药品检定研究院,国家药物安全评价监测中心,北京 100176;
    3沈阳药科大学功能食品与葡萄酒学院,辽宁 沈阳 110016;
    4国家药典委员会,北京 100061;
    5药品监管科学全国重点实验室,北京100061;
    6中国食品药品检定研究院中药民族药检定所,北京 100050
  • 收稿日期:2024-06-26 出版日期:2024-12-15 发布日期:2024-12-16
  • 通讯作者: *汪祺,女,博士,研究员,中药质量与安全性评价。E-mail: sansan8251@sohu.com,#为共同通信作者。
  • 作者简介:李妍怡,女,在读博士,中药质量与安全评价。△为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目（82374033）

Identification of Hepatotoxic Components of Polygoni Multiflori Radix Based on Material Basis Combined with Heparg Cell Experiments

LI Yanyi1, WEN Hairuo2△, YANG Yanrong3, MA Shuangcheng4,5#, WANG Qi6,*   

  1. 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102400, China;
    2National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100176, China;
    3Shenyang Pharmaceutical University, School of Functional Food and Wine, Shenyang Liaoning 110016, China;
    4Chinese Pharmacopoeia Commission, Beijing 100061, China;
    5State Key Laboratorg of Drug Regulactorg Science, Beijing 100061, China;
    6Institute of Chinese Traditional Medicine and Ethnic Medicine, National Institutes for Food and Drug Control, Beijing 100050, China
  • Received:2024-06-26 Online:2024-12-15 Published:2024-12-16

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摘要： 目的 通过不同批次何首乌样品细胞毒性的差异,探究其潜在肝损伤成分。方法 采用超高效液相色谱-三重四极杆质谱法（UPLC-QQQ-MS/MS）对何首乌成分进行定量检测,运用聚类分析法（Hierarchical Cluster Analysis, HCA）对22批何首乌样品进行聚类;以HepaRG细胞半数抑制浓度（Half Inhibitory Concentration, IC50）为指标,对不同类别何首乌样品进行毒性评价,获取不同组别毒性差异。随后,通过正交偏最小二乘-判别分析（Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA）揭示肝细胞毒性作用与何首乌物质基础的相关性,筛选毒性差异成分。结果 22批样品可依据共有化合物分为A、B、C 3组。HepaRG细胞结果表明,3组间毒性作用B组<A组<C组。不同毒性A、B、C组间OPLS-DA模型判别率良好,得到3个变量重要性投影（Variable Importance in Projection,VIP）>1的潜在毒性成分。结论 不同组别何首乌样品,存在毒性差异,其中2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷、大黄素-8-O-β-D-葡萄糖苷、儿茶素可能为潜在毒性成分。

关键词: 何首乌, 肝损伤, HepaRG细胞, 聚类分析, 正交偏最小二乘-判别分析, 2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷, 大黄素-8-O-β-D-葡萄糖苷, 儿茶素

Abstract: Objective To explore potential hepatotoxic components based on the differences in cytotoxicity between different batches of Polygoni Multiflori Radix(PM). Methods Ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS) was used for quantitative detection of PM while hierarchical cluster analysis was used to classify samples. The half inhibitory concentration (IC50) of HepaRG cells was used as the index to evaluate the toxicity of categorized samples and to reveal the differences between different groups. Orthogonal partial least squares discriminant analysis was used to identify the differences in toxicity between different groups and screen for differential components. Results Twenty-two batches of samples were divided into categories A, B, and C based on common compounds. The IC50 of HepaRG cells indicated that the three groups of samples were significantly different in terms of toxicity, which was the highest in group B, followed by group A and group C. The results of OPLS-DA suggested that the discrimination rate of the models between groups A, B, and C was good, and three potential toxic components with VIP>1 were obtained. Conclusion Different categories of PM samples exhibit differences in toxicity. trans-2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), emodin-8-O-β-D-glucoside (EG) and catechin are potential toxic components of PM.

Key words: Polygoni Multiflori Radix, Liver Injury, HepaRG Cells, HCA, OPLS-DA, THSG, EG, Catechin

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