基于网络药理学探讨复方积雪草抗肾纤维化的分子机制

Centella compound anti-renal Fibrosis and the Underlying Molecular Events:A Network Pharmacological Analysis

目的通过网络药理学方法研究复方积雪草主要活性成分治疗肾纤维化的作用机制。方法在TCMSP数据库中筛选与复方积雪草主要组分相关的活性成分和靶点,利用GeneCards数据库检索与肾纤维化相关靶点并与活性成分靶点取交集。采用Cytoscape软件构建蛋白与蛋白相互作用(PPI)网络、化合物-靶点网络图、中药-化合物-靶点网络图,筛选核心靶点,分子对接验证化合物与靶点的结合能力;将获得的核心靶点利用STRING进行基因通路的富集分析,进而分析网络和作用机制。结果得到复方积雪草活性成分靶点203个,获得肾纤维化靶点5219个,共同靶点177个。筛选出核心靶点36个。分子对接验证结果化合物与靶点具有较好的结合能力。GO富集分析分别获得可靠性排名TOP10的主要分子功能(MF)、主要细胞组分(CC)和主要生物学过程(BP)。得到核心靶点之间的PPI网络图、化合物-核心靶点网络图和草药-化合物-核心靶点网络图。肿瘤相关通路显著性最高。结论初步系统分析了复方积雪草治疗肾纤维化的科学性及分子机制。

Objective This network-pharmacology study explored the mechanisms of the main active ingredients of Centellaasiatica Compound action on the inhibition of renal fibrosis.Methods The active ingredients of Centellaasiatica Compound and their target genes were analyzed using the TCMSP database.The genes that are related to renal fibrosis were retrieved from the GeneCards database and intersected with the target genes of the active ingredients of Centellaasiatica Compound.The protein-protein interaction(PPI)network,the compound-target interaction network,and the herb-compound-target network were constructed by Cytoscape software to identify the core targets.The combining ability of the compound and targets was evaluated using the molecular docking analysis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses of core targets were performed based on the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)platform.Results This study obtained 203 target genes from TCMSP database analysis and retrieved 5219 target genes related to renal fibrosis,leading to the identification of 177 common targets and 36 core targets.The molecular docking analysis showed that this compound had a good binding ability to each of the targets.The top 10 GO terms of the major molecular functions(MF),major cellular components(CC),and major biological processes(BP)were identified and the core targets interaction network,a compound-core target network,and a herb-compound-core target network were also plotted.The enrichment analysis revealed tumor pathway as one of the highly significant pathways in renal fibrosis.Conclusion This study revealed the scientific nature and molecular mechanism of Centellaasiatica Compound in the treatment of renal fibrosis,which could provide a molecular basis for further study of its molecular mechanism.