基于网络药理学和分子对接分析消炎利胆片治疗慢性胆囊炎的作用机制

Mechanism of action of Xiaoyan Lidan tablets in treatment of chronic cholecystitis:A study based on network pharmacology and molecular docking

目的:通过网络药理学方法预测消炎利胆片治疗慢性胆囊炎的核心有效成分和靶点,并通过分子对接初步验证结果的稳健性。方法:利用TCMSP、CancerHSP、BATMAN-TCM数据库检索消炎利胆片有效成分及对应靶点,借助UniProt数据库对靶点进行规范化。通过GeneCards、DisGeNET和OMIM数据库检索慢性胆囊炎相关靶点。运用R软件筛选药物与疾病交集靶点;分别通过Bioconductor平台、STRING数据库对交集靶点进行富集分析和蛋白相互作用分析。通过Cytoscape软件筛选出核心有效成分和靶点,将核心有效成分与核心靶点进行分子对接评估结合活性以验证结果稳健性。结果:共获得23种有效成分,对应190个药物作用靶点,从数据库中获取723个疾病相关靶点,药物与疾病之间有48个交集基因;富集结果显示多与细胞对炎症反应相关,筛选得到槲皮素、汉黄芩素、非瑟酮等核心有效成分,白细胞介素-1β(IL-1β)、基质金属蛋白酶9(MMP9)、血管内皮生长因子A(VEGFA)等核心靶点;分子对接结果显示核心有效成分与核心靶点之间均有较好的结合活性。结论:消炎利胆片中的槲皮素、汉黄芩素、非瑟酮等核心有效成分可能通过参与调控炎症相关信号通路作用于IL-1β、MMP9、VEGFA等核心靶点,从而发挥治疗慢性胆囊炎的作用。

Objective:To investigate the core effective constituents and targets of Xiaoyan Lidan tablets in the treatment of chronic cholecystitis based on network pharmacology,as well as the robustness of results based on molecular docking.Methods:TCMSP,CancerHSP,and BATMAN-TCM databases were searched to obtain the effective constituents of Xiaoyan Lidan tablets and their corresponding targets,and UniProt database was used for the standardization of targets.GeneCards,DisGeNET,and OMIM databases were used to search for the targets associated with chronic cholecystitis.R software was used to obtain the intersecting targets of the drug and the disease,and Bioconductor platform and STRING database were used to perform the enrichment analysis and protein-protein interaction analysis of the intersecting targets.Cytoscape software was used to obtain the core effective constituents and targets,and molecular docking was performed for the core effective constituents and targets to evaluate binding activity and validate the robustness of results.Results:A total of 23 effective constituents and 190 corresponding action targets were obtained,and 723 disease-related targets were obtained from databases.There were 48 intersecting targets between the drug and the disease.The enrichment analysis showed that the targets were mainly associated with cell response to inflammation,and core effective constituents were obtained,including quercetin,wogonin,and fisetin,as well as the core targets including interleukin-1β(IL-1β),matrix metalloproteinase-9(MMP9),and vascular endothelial growth factor A(VEGFA).Molecular docking showed good binding activity between the core effective constituents and the core targets.Conclusion:The core effective constituents of Xiaoyan Lidan tablets,including quercetin,wogonin,and fisetin,exert a therapeutic effect on chronic cholecystitis by regulating inflammation-related signaling pathways to act on the core targets such as IL-1β,MMP9,and VEGFA.