目的 基于網絡毒理學和分子對接技術探究補骨脂酚致肝毒性的潛在機制。方法 通過TCM-BATMAN挖掘補骨脂酚靶點，DisGeNET挖掘肝毒性基因；Cytoscape 3.7.0分別構建補骨脂酚靶點和肝毒性基因蛋白互作關系（PPI）網絡，并Merge取交集，運用軟件中插件分析獲得關鍵靶點，構建生物學總調控網絡，并對其進行基因本體論（gene ontology，GO）和京都基因與基因組百科全書（Kyoto encyclopedia of genes and genomes，KEGG）富集分析；分子對接評價補骨脂酚與潛在關鍵靶點結合的親和力。結果 共獲得補骨脂酚靶點3 952個，肝毒性基因6 025個和交集基因2 221個。經分析，補骨脂酚主要作用于TP53、HSP90AA1、EP300等關鍵靶點，參與氧化應激反應與細胞增殖、分化、凋亡過程的調控，涉及多種酶調控等生物過程，主要通過PI3K-Akt、MAPK、細胞周期等信號通路引起肝毒性。補骨脂酚與EP300、HSP90AA1靶點的親和力最強，能夠與二者的結合口袋形成較強的疏水作用，total score值為8.858 2、7.217 8。結論 補骨脂酚致肝毒性具有多靶點、多途徑的作用規(guī)律，主要通過PI3K-Akt、MAPK、細胞周期等信號通路引起肝毒性。

Objective To explore the potential mechanism of bakuchiol induced hepatotoxicity based on network toxicology and molecular docking. Methods TCM-BATMAN was used to mine drug targets, and DisGeNET was used to mine disease genes. Cytoscape3.7.0 was used to construct bakuchiol targets and hepatotoxic genes PPI network respectively, and Merge was used to obtain the intersection. The key targets were obtained by plug-in analysis of the software, and the overall regulatory network of biology was constructed. GO and KEGG were performed on key targets. The binding affinity of bakuchiol to potential target genes was evaluated by molecular docking. Results There were 3 952 component targets, 6 025 hepatotoxic genes and 2 221 intersection genes. Through in-depth analysis, bakuchiol mainly acted on TP53, HSP90AA1, EP300 and other key targets. It was mainly involved in the regulation of oxidative stress response and cell proliferation, differentiation and apoptosis, involving a variety of enzyme regulation and other biological processes, regulating PI3K-Akt, MAPK and cell cycle signaling pathways, causing hepatotoxicity. Bakuchiol had the strongest affinity with EP300 and HSP90AA1 target genes, and could form strong hydrophobic interaction with their binding pocket. The total score was 8.858 2 and 7.217 8. Conclusion Psoralen induced hepatotoxicity has the law of multi-target and multi-channel action, mainly through PI3K-Akt, MAPK, cell cycle and other signal pathways.

R285.5

山東省大學生創(chuàng)新創(chuàng)業(yè)訓練計劃項目（S202110441014）；國家自然科學基金資助項目（81903780）；山東省中醫(yī)藥科技發(fā)展計劃項目（2019-0030）；山東中醫(yī)藥大學中藥資源保護與質量評價青創(chuàng)團隊支持項目