基于网络药理学与分子对接的蒺藜皂苷D抗肺纤维化的作用机制研究*

目的: 采用网络药理学和分子对接技术探讨蒺藜皂苷D治疗肺纤维化可能的分子机制。方法: 采用SwissTargetPrediction数据库收集蒺藜皂苷D靶点,通过UniProt数据库将相应靶点蛋白名称进行标准化;通过DrugBank数据库、GeneCards数据库和OMIM数据库检索“pulmonary fibrosis”,获取肺纤维化疾病靶点;通过韦恩图获取蒺藜皂苷D和肺纤维化的共同靶点,并进行蛋白-蛋白相互作用(PPI)网络分析、基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路分析。利用分子对接技术验证蒺藜皂苷D与核心靶点的结合能力。结果: 获取蒺藜皂苷D 43个潜在靶点,肺纤维化疾病1 492个相关靶点,蒺藜皂苷D与肺纤维化共同靶点17个,PPI网络中自由度排名前8个靶点分别为MAPK3、PPARG、IL6、TNF、VEGFA、TGFβ1、FGF2和STAT3;GO功能富集注释得到生物学过程(BP)条目418条,细胞组成(CC)条目22条,分子功能(MF)条目29条;KEGG通路分析得到69条信号通路;分子对接提示MAPK3、FGF2、STAT3、IL6、PPARG与蒺藜皂苷D的结合能均≤-5.0 kcal/mol。结论: 蒺藜皂苷D通过多靶点、多途径的效应发挥治疗肺纤维化的生物活性,其可能通过MAPK3、FGF2、STAT3、IL6和PPARG等靶点调控MAPK信号通路和PI3K-Akt信号通路治疗肺纤维化。

Mechanism of tribulus terrestrosin D in treatment of pulmonary fibrosis based on network pharmacology and molecular docking

Objective: To explore the possible molecular mechanism of terrestrosin D in the treatment of pulmonary fibrosis by network pharmacology and molecular docking technology. Methods: SwissTargetPrediction database was used to collect the terrestrosin D targets, and the corresponding targets protein names were standardized by UniProt database. Disease targets were obtained by searching "Pulmonary fibrosis" in DrugBank database, GeneCards database and OMIM database, and common targets of terrestrosin D and pulmonary fibrosis were obtained by Venn diagram. PPI network analysis, GO functional enrichment analysis and KEGG pathway analysis were performed. The binding ability of terrestrosin D to the core target was verified by molecular docking technique. Results: 43 potential targets of terrestrosin D, 1492 related targets of pulmonary fibrosis, 17 common targets of terrestrosin D and pulmonary fibrosis were obtained. The top 8 targets in PPI network were MAPK3, PPARG, IL6, TNF, VEGFA, TGFβ1, FGF2 and STAT3. GO functional enrichment annotation obtained 418 items of biological process (BP), 22 items of cell composition (CC) and 29 items of molecular function (MF). KEGG pathway analysis revealed 69 signaling pathways. Molecular docking showed that the binding energies of MAPK3, FGF2, STAT3, IL6, PPARG and terrestrosin D were all ≤-5.0 kcal/mol. Conclusion: Terrestrosin D exerts its biological activity in the treatment of pulmonary fibrosis through multi-target and multi-pathway effects, and it may regulate MAPK signaling pathway and PI3K-Akt signaling pathway through MAPK3, FGF2, STAT3, IL6 and PPARG.