目的 通過網(wǎng)絡藥理學及分子對接技術(shù)探究川楝子肝毒性機制。方法 通過TCMSP、PubChem、SwissADME數(shù)據(jù)庫及文獻檢索篩選川楝子的潛在毒性成分，利用SwissTargetPrediction數(shù)據(jù)庫預測潛在毒性成分的作用靶點，再通過GeneCards數(shù)據(jù)庫搜索與肝臟損傷相關(guān)的靶點，將毒性成分預測靶點與肝臟損傷靶點取交集靶點，獲得毒性成分肝臟潛在作用靶點，再利用軟件Cytoscape 3.8.2版進行毒性成分–預測靶點、毒性成分–潛在作用靶點、蛋白相互作用（PPI）網(wǎng)絡、毒性成分–潛在作用靶點–核心通路網(wǎng)絡的構(gòu)建，采用AutoDock 1.5.6版進行分子對接，并應用PyMOL軟件對對接結(jié)果進行可視化示例。結(jié)果 篩選得到6個川楝子潛在毒性化合物，分別是toosandanin、meliasenin B、trichilinin D、1-O-tigloy-1-O-debenzoylohchinal、butenolide、5-hydxoymethylfurfural，與肝臟損傷共同作用靶點103個。GO和KEGG結(jié)果顯示，川楝子通過蛋白質(zhì)磷酸化、凋亡過程的負調(diào)控、對異種生物刺激的反應、酶激活的正向調(diào)控等過程引起肝臟毒性。分子對接結(jié)果顯示，川楝子中toosandanin、trichilinin D、1-O-tigloy-1-O-debenzoylohchinal與關(guān)鍵靶點具有較好的結(jié)合能力。結(jié)論 應用網(wǎng)絡藥理學及分子對接技術(shù)對川楝子致肝毒成分、機制、靶點、通路進行了初步探索，為進一步對川楝子的臨床應用研究和效應機制提供數(shù)據(jù)支持。

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.

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遵義醫(yī)科大學未來“醫(yī)技名匠”人才培養(yǎng)計劃（遵醫(yī)未來醫(yī)技名匠[2022]03）