基于网络药理学及分子对接分析花椒抗结直肠癌的作用机制

Analysis on the function mechanism of anti-colorectal cancer of pericarpium zanthoxyli based on network pharmacology and molecular docking

目的基于网络药理学及分子对接探究花椒治疗结直肠癌(CRC)的作用机制。方法在TCMSP、PubChem、SwissTargetPridiction数据库中获取花椒的有效成分和作用靶点;在GeneCards、OMIM、TTD数据库获取疾病靶点;利用STRING数据库进行蛋白质相互作用(PPI)分析;利用Cytoscape软件进行拓扑分析,筛选出关键靶点;使用DAVID数据库对关键靶点进行基因本体(GO)和基因组京都百科全书(KEGG)富集分析;最后通过AutoDock Vina 1.2.0软件对花椒主要活性成分与关键靶点进行分子对接验证。结果花椒抗CRC有5个核心成分,即香草木宁、茵芋碱、香叶木素、槲皮素、异鼠李素;关键靶点涉及AKT1、PIK3R1、EGFR等;主要通路有癌症、PI3K-Akt等;分子对接结果显示花椒抗CRC的主要核心成分和核心靶点之间有较好的结合活性。结论花椒抗CRC的作用机制可能是其有效成分作用于AKT1、PIK3R1等关键靶点及癌症相关信号通路,从而抑制肿瘤细胞的增殖并促进其凋亡。

Objective To investigate the function mechanism of pericarpium zanthoxyli in the treatment of colorectal cancer(CRC)based on network pharmacology and molecular docking.Methods The effective ingredients and function targets of pericarpium zanthoxyli were obtained from TCMSP,PubChem and SwissTargetPridiction databases.The disease targets were obtained from GeneCards,OMIM and TTD databases;Protein-protein interaction(PPI)analysis was performed by using STRING database.Topology analysis was carried out by Cytoscape software to screen out key targets.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed on key targets using DAVID database.Finally,molecular docking validation was performed on the main active ingredients and key targets of pericarpium zanthoxyli using AutoDock Vina 1.2.0 software.Results Pericarpium zanthoxyli had 5 core ingredients against CRC,namely kokusaginine,skimmianine,diosmetin,quercetin and isorhamnetin;The key targets included AKT1,PIK3R1,EGFR,etc.;The main pathways were cancer,PI3K-Akt,etc..The results of molecular docking showed that pericarpium zanthoxyli had good binding activity between the main core components and the core target.Conclusion The anti-CRC function mechanism of pericarpium zanthoxyli may be that its effective ingredients function on key targets such as AKT1 and PIK3R1 and cancer-related signal pathways,thus inhibiting the proliferation of tumor cells and promoting their apoptosis.