目的 利用网络药理学和分子对接技术探讨大黄肝毒性的分子作用机制。方法 在TCMSP检索大黄活性成分及文献获取潜在肝毒性成分，利用Swiss Target Prediction数据库获取成分靶点，通过GeneCards和OMIM数据库获取人类肝毒性相关靶点。利用STRING数据库将Venn图获得成分与疾病共同靶标进行（PPI）网络分析，用Cytoscape软件构建“大黄成分–肝毒性作用靶点”网络，并且利用DAVID数据库进行基因本体（GO）功能富集和京都基因与基因组百科全书（KEGG）（KEGG）通路富集。将部分肝毒性核心成分和关键靶点进行分子对接。结果 共获取大黄潜在肝毒性成分21种，对应靶点724个，人类肝毒性相关靶点957个，大黄与肝毒性的共同靶点151个，核心成分可能是大黄酸、大黄酚、β-谷甾醇、大黄素-1-O-β-D-葡萄糖硫苷、大黄素甲醚二葡萄糖苷、芦荟大黄素等，关键靶点可能是白蛋白（ALB）、蛋白激酶B1（Akt1）、肿瘤蛋白p53（TP53）等。KEGG通路显示癌症通路、前列腺癌通路等可能在大黄肝毒性中起关键作用。分子对接结果表明，大黄肝毒性核心成分与关键靶点对接良好。结论 大黄通过多成分、多靶点、多通路机制导致肝毒性作用。

Objective To explore the mechanism of hepatotoxicity of Rhei Radix et Rhizoma by network pharmacology and molecular docking. Methods Potential hepatotoxic components of rhubarb were retrieved from TCMSP and literature. The component target was obtained by Swiss Target Prediction database, and the human hepatotoxic related targets were obtained by GeneCards and OMIM databases. The components obtained from Venn diagram and disease common targets were analyzed using STRING database for PPI network analysis, the “Rhei Radix et Rhizoma - hepatotoxicity targets” network was constructed using Cytoscape software, and the GO and KEGG pathway enrichment were performed using DAVID database. Some of the core components of hepatotoxicity were moleculically docked with key targets. Results A total of 724 targets corresponding to 21 potential hepatotoxic components of Rhei Radix et Rhizoma, 957 targets related to human hepatotoxicity, and 151 common targets of Rhei Radix et Rhizoma and hepatotoxicity were obtained. The core components of rhubarb may be rhein, chrysophanol, β-sitosterol, emodin-1-O-β-D-glucoside, emodin methyl ether diglucoside, aloe emodin, etc. The key targets may be ALB, AKT1, TP53, etc. KEGG pathway showed 139 signaling pathways indicating that cancer pathway and prostate cancer pathway may play a key role in the hepatotoxicity of Rhei Radix et Rhizoma. The results of molecular docking showed that the core components of Rhei Radix et Rhizoma hepatotoxicity interacted well with key targets. Conclusion Rhei Radix et Rhizoma causes hepatotoxicity through a multi-component, multi-target-multi-pathway mechanism.

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