基于网络药理学和分子对接技术探讨独活对软骨细胞影响的分子机制

Molecular Mechanism of Angelicae Pubescentis Radix on Chondrocyte Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接的方法研究独活对软骨细胞的干预机制。方法:使用TCMSP、Swiss Target Prediction等数据库获取独活的活性化合物、作用靶点和软骨细胞相关基因。使用Cytoscape软件建立“药物-活性成分-作用靶点-通路网络”图。使用String数据库对潜在靶点进行分析,得到蛋白互作关系图。使用分子对接验证独活活性化合物与关键靶点之间的结合。结果:得到独活活性化合物9个,与软骨细胞相关靶点142个。最终筛选二氢欧山芹醇乙酯、当归素和欧前胡素为关键活性化合物,GAPDH、VEGFA和EGFR为主要靶标。分子对接结果显示,筛选的化合物与主要靶标均具有良好的结合作用,涉及软骨细胞增殖、凋亡等生物过程。结论:独活具有二氢欧山芹醇乙酯、当归素和欧前胡素等多个活性成分,通过多靶点多通路影响软骨细胞,进而发挥治疗骨关节炎的作用。

Objective:To study the intervention mechanism of Angelicae Pubescentis Radix on chondrocytes based on the methods of network pharmacology and molecular docking.Methods:The databases of TCMSP and Swiss Target Prediction were applied to obtain the active compounds,targets and chondrocyte-related genes of Angelicae Pubescentis Radix.The map of‘drug-active ingredient-target of action-pathway network’was established by using Cytoscape software.String database was used to analyze potential targets and obtain protein interaction diagrams.Molecular docking method was applied to verify the binding between the active compounds and the key targets.Results:9 active compounds and 142 targets related to chondrocytes were obtained.O-Acetylcolumbianetin,Angelicone and Ammidin were finally screened out as the key active compounds,GAPDH,VEGFA and EGFR as the main targets.The molecular docking results showed that the screened compounds had good binding effects with the main targets,involving biological processes of cartilage cell proliferation and apoptosis.Conclusion:Angelicae Pubescentis Radix has multiple active ingredients,such as O-Acetylcolumbianetin,Angelicone and Ammidin,which can affect chondrocytes through multiple targets and multiple pathways,thus to play a role in treating osteoarthritis.