以法尼醇X受体为作用靶点的何首乌中肝毒性成分的筛选

doi:10.19803/j.1672-8629.2022.06.10

中国药物警戒 ›› 2022, Vol. 19 ›› Issue (6): 630-634.
DOI: 10.19803/j.1672-8629.2022.06.10

• 何首乌质量及安全性评价专栏（一） • 上一篇下一篇

以法尼醇X受体为作用靶点的何首乌中肝毒性成分的筛选

汪祺, 文海若^#, 马双成^*

中国食品药品检定研究院,北京 100050

收稿日期:2021-07-08 出版日期:2022-06-15 发布日期:2022-06-13
通讯作者: ^* 马双成,男,博士,研究员,中药民族药物质基础与质量安全评价研究。E-mail：masc@nifdc.org.cn;^#为共同通信作者。
作者简介:汪祺,女,博士,研究员,中药毒理。
基金资助:
国家自然科学基金资助项目(81973476)

Screening of hepatotoxic components in Polygonum multiflorum by taking FXR nuclear receptors as targets

WANG Qi, WEN Hairuo^#, MA Shuangcheng^*

National Institutes for Food and Drug Control, Beijing 100050, China

Received:2021-07-08 Online:2022-06-15 Published:2022-06-13

摘要/Abstract

摘要： 目的建立以法尼醇X受体（farnesoid X receptor,FXR）为作用靶点的何首乌中肝毒性成分快速筛选方法。方法首先运用计算机分子对接技术,使用Discovery Studio 2.5软件将目标化合物与FXR进行分子对接,以FXR抑制剂作为参考对象对目标化合物进行虚拟筛选;之后,采用细胞计数试剂盒法（cell counting kit-8,CCK-8）考察目标化合物处理24 h后对人源肝永生化肝细胞HepaRG的毒性强弱,并采用实时聚合酶链反应（PCR）技术测定目标化合物对HepaRG细胞的FXR基因相对表达量的影响。结果分子对接结果显示,何首乌中芦荟大黄素-8-O-β-D-葡萄糖苷及大黄素-8-O-β-D-葡萄糖苷等9个成分为FXR潜在抑制剂;体外细胞毒性试验进一步证实芦荟大黄素-8-O-β-D-葡萄糖苷及大黄素-8-O-β-D-葡萄糖苷均具肝细胞毒性作用,同时可明显抑制FXR基因表达水平。结论以FXR分子对接技术为切入点,有效预测何首乌中潜在肝毒性成分,实现了快速高效的高通量筛选,为中药安全性评价提供新思路。

关键词: 何首乌, 法尼醇X受体, 分子对接, 肝毒性, 安全性评价

Abstract: Objective To establish a rapid method for screening hepatotoxic components in Polygonum multiflorum (P.M.) by taking the farnesoid X receptor (FXR) as the target. Methods First of all, computer molecular docking technology was adopted, Discovery Studio 2.5 software was used to molecularly dock the target compounds with the FXR, and the target compounds were screened virtually with FXR inhibitors as the reference objects. Next, the cell counting kit (CCK-8) method was used to investigate the toxicity of the target compounds on HepaRG after 24 h of treatment, while real-time PCR was used to determine the effects of the target compounds on the relative expression level of FXR genes in HepaRG cells. Results The molecular docking results showed that nine components in Polygonum multiflorum, including aloe-emodin-8-O-β-D-glucoside and emodin-8-O-β-D-glucoside, were potential inhibitors of FXR. In vitro cytotoxicity test further confirmed that both aloe-emodin-8-O-β-D-glucoside and emodin-8-O-β-D-glucoside had hepatotoxicity that could significantly inhibit the expression level of FXR genes. Conclusion This study effectively predicts the potential hepatotoxic components of Polygonum multiflorum, and a rapid and efficient high-throughput hepatoxicity screening method is established, which is expected to provide new ideas for safety evaluation of traditional Chinese medicine.

Key words: Polygonum multiflorum, farnesoid X receptor, molecular docking, hepatotoxicity, safety evaluation

中图分类号:

R961
R969.3

汪祺, 文海若, 马双成. 以法尼醇X受体为作用靶点的何首乌中肝毒性成分的筛选[J]. 中国药物警戒, 2022, 19(6): 630-634.

WANG Qi, WEN Hairuo, MA Shuangcheng. Screening of hepatotoxic components in Polygonum multiflorum by taking FXR nuclear receptors as targets[J]. Chinese Journal of Pharmacovigilance, 2022, 19(6): 630-634.

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以法尼醇X受体为作用靶点的何首乌中肝毒性成分的筛选

Screening of hepatotoxic components in Polygonum multiflorum by taking FXR nuclear receptors as targets

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