基于网络药理学和分子对接技术分析川楝子致肝毒性机制

目的 通过网络药理学及分子对接技术探究川楝子肝毒性机制。方法 通过TCMSP、PubChem、SwissADME数据库及文献检索筛选川楝子的潜在毒性成分，利用SwissTargetPrediction数据库预测潜在毒性成分的作用靶点，再通过GeneCards数据库搜索与肝脏损伤相关的靶点，将毒性成分预测靶点与肝脏损伤靶点取交集靶点，获得毒性成分肝脏潜在作用靶点，再利用软件Cytoscape 3.8.2版进行毒性成分–预测靶点、毒性成分–潜在作用靶点、蛋白相互作用（PPI）网络、毒性成分–潜在作用靶点–核心通路网络的构建，采用AutoDock 1.5.6版进行分子对接，并应用PyMOL软件对对接结果进行可视化示例。结果 筛选得到6个川楝子潜在毒性化合物，分别是toosandanin、meliasenin B、trichilinin D、1-O-tigloy-1-O-debenzoylohchinal、butenolide、5-hydxoymethylfurfural，与肝脏损伤共同作用靶点103个。GO和KEGG结果显示，川楝子通过蛋白质磷酸化、凋亡过程的负调控、对异种生物刺激的反应、酶激活的正向调控等过程引起肝脏毒性。分子对接结果显示，川楝子中toosandanin、trichilinin D、1-O-tigloy-1-O-debenzoylohchinal与关键靶点具有较好的结合能力。结论 应用网络药理学及分子对接技术对川楝子致肝毒成分、机制、靶点、通路进行了初步探索，为进一步对川楝子的临床应用研究和效应机制提供数据支持。

Hepatotoxicity mechanism of Toosendan Fructus based on network pharmacology and molecular docking techniques

Objective To investigate the mechanism of hepatotoxicity of Toosendan Fructus by network pharmacology and molecular docking technique. Methods The potential toxic components of Toosendan Fructus were screened through TCMSP, PubChem, SwissADME databases, and literature search, the targets of potential toxic components were predicted using SwissTargetPrediction database, and then the targets related to liver injury were searched through GeneCards database, and the intersecting targets between the predicted targets of the toxic components and liver injury targets were taken to obtain the potential targets of action of the toxic components in the liver. The intersection target was taken to obtain the liver potential action target of toxic ingredients, and then the software Cytoscape version 3.8.2 was used for the construction of toxic ingredient-predicted target, toxic ingredient-potential action target, PPI network, and toxic ingredient-potential action target-core pathway network, and the molecular docking was carried out by using the version of AutoDock 1.5.6 and the open source software PyMOL was applied to visualize the docking results. The docking results were visualized as examples. Results Six potentially toxic compounds of Toosendan Fructus, namely toosandanin, meliasenin B, trichilinin D, 1-O-tigloy-1-O-debenzoylohchinal, butenolide, and 5-hydxoymethylfurfural were screened for liver damage with common targets of action 103. GO and KEGG results showed that Toosendan Fructus induced hepatotoxicity through processes such as protein phosphorylation, negative regulation of apoptotic processes, response to xenobiotic stimuli, and positive regulation of enzyme activation. Molecular docking results showed that three potentially toxic components of Toosendan Fructus, toosandanin, trichilinin D, and 1-O-tigloy-1-O-debenzoylohchinal, had good binding capacity to the key targets. Conclusion The preliminary exploration of hepatotoxic components, mechanisms, targets, and pathways of Toosendan Fructus was carried out by applying network pharmacology and molecular docking techniques to provide data support for further clinical application studies and effect mechanisms of Toosendan Fructus.