基于网络药理学的延胡索镇痛活性作用研究

Study on Analgesic Activity of Corydalis yanhusuo Based on Network Pharmacology

目的:通过网络药理学方法,筛选延胡索镇痛作用的药效物质和作用靶点,系统分析延胡索镇痛作用的多成分-多靶点-多通路性质。方法:基于TCMSP数据库,结合药动学参数筛选出延胡索的活性成分,通过SymMap数据库获得延胡索活性成分的靶点简称。采用GeneCards和OMIM数据库筛选疼痛相关靶点,做VENN图获得延胡索镇痛作用的直接靶点。利用String数据库获得延胡索镇痛作用靶点的蛋白质相互作用信息,利用DAVID数据库获得基因本体论功能(GO)和通路富集分析结果,最后建立活性成分、作用靶点、GO和通路之间的关联关系,构建延胡索镇痛的“成分-靶点-GO功能-信号通路”,通过网络分析筛选核心成分和靶点。结果:共筛选出22个核心成分和13个核心靶点,核心成分主要为延胡索生物碱类化合物,还包括槲皮素和香豆素;核心靶点包括PTGS2、IL6、TNF、TGFB1、IL1B、VEGFA、IL10、ESR1、AKT1、CXCL8、TP53、IFNG、EGFR;涉及到的GO功能主要包括一氧化氮生物合成的正调控、基因表达的正调控、炎症反应、细胞外间隙、细胞因子活性有关;调节的信号通路主要包括类风湿性关节炎、癌症的途径、炎症性肠病、细胞因子-细胞因子受体相互作用等。结论:采用网络药理学的方法,从整体上揭示了延胡索的镇痛作用药效物质和机制,可为下一步的实验研究提供依据。

Objective:The analgesic substances and targets of Corydalis yanhusuo(YHS) were screened by network pharmacology.The analgesic effect of multicomponents-multitargets-multipathways of YHS was systematically analyzed.Mehtods:The active ingredients of YHS were screened out based on TCMSP database and pharmacokinetic parameters while the target symbols were obtained through SymMap database.The pain-related targets were screened by GeneCards and OMIM database,and the direct targets of the analgesic effect of YHS were obtained by VENN map.The protein interaction information was obtained by the String database while the gene ontology(GO) function and pathway enrich and analyze results were obtained by DAVID database.The“component-target-GO-pathway”of analgesia for YHS was constructed through the established relationship between active ingredients,targets,GO and pathways.Finally,the key components and targets were screened by network analysis.Results:A total of 22 key components and 13 key targets were obtained.The core components were mainly YHS alkaloids,quercetin and(S)-Scoulerine while the core targets include PTGS2,IL6,TNF,TGFB1,IL1 B,VEGFA,IL10,ESR1,AKT1,CXCL8,TP53,IFNG,EGFR.The GO functions involved mainly include positive regulation of nitric oxide biosynthetic and gene expression,inflammatory response,extracellular space and cytokine activity.The regulated signal pathways mainly include rheumatoid arthritis,cancer pathways,inflammatory bowel disease and cytokine-cytokine receptor interaction.Conclusion:The network pharmacology method was used to reveal the analgesic substances and mechanisms of YHS.It could provide a basis for further experimental research.