基于网络药理学及分子对接方法探讨金铃子散治疗神经病理性疼痛的作用机制

Study on the Potential Mechanism of Jinlingzisan in the Treatment of Neuropathic Pain based on Network Phar-macology and Molecular Docking Method

目的运用网络药理学和分子对接的方法研究及探讨中药方剂金铃子散治疗神经病理性疼痛的作用机制。方法通过检索中药系统药理学分析平台数据库(TCMSP),筛选出川楝子和延胡索的有效活性成分及作用靶点;同时,从GeneCards、OMIM、PharmGkb、TTD及DrugBank数据库收集整理神经病理性疼痛的相关靶点,取两者的交集得到药物-疾病蛋白靶点,筛选出共有靶点导入String分析平台进行PPI网络构建,通过Cycoscape软件将结果进行网络化展示;通过R语言筛选出核心靶点蛋白,再用薛定谔Maestro软件进行分子对接验证;借助R语言,利用基因本体(GO)和京都基因和基因组百科全书(KEGG)数据库对交集靶点分别进行GO功能富集分析及KEGG通路富集分析,同时结合相关文献,分析金铃子散治疗神经病理性疼痛的可能机制。结果根据口服生物利用度(OB)与类药性(DL)筛选出金铃子散58个有效活性成分和1919个作用靶点;通过疾病数据库检索到与神经病理性疼痛相关的已知疾病靶点1420个;筛选出55个核心活性成份和30个核心靶点蛋白,分子对接显示槲皮素(Quercetin)、金黄紫堇碱((S)-Scoulerine)和延胡索乙素(Tetrahydropalmatine)可能为关键活性成份;金铃子散主要作用于神经活性配体-受体相互作用、钙信号通路及晚期糖基化终末产物(AGE)及其受体(RAGE)协同等信号通路。结论金铃子散通过其多成份、多靶点、多通路治疗神经病理性疼痛。

Objective To explore the mechanism of Jinlingzisan in the treatment of neuropathic pain based on network pharmacology and molecular docking.Methods The effective active ingredients and potential targets of Jinlingzisan are collected by the traditional Chinese medicine systems pharmacology analysis platfom database(TCMSP);The targets of neuropathic pain were collected from the GeneCards,OMIM,PharmGkb,TTD and the DrugBank database,The common targets of disease-drug were selected based on String analysis platform for protein-protein interaction(PPI)network construction,And the results were displayed by Cycoscape software;The core target proteins were screened by R language,and then to verify its molecular dockingSchrodinger Maestro software was used;With the Bioconductor collection toolkit of R software,using gene ontology(GO)and Kyoto Encyclopedia of Gene and Genome(KEGG)database,the GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersection target were carried out,and combined with the related literature,the possible mechanism of neuropathic pain treated by Jinlingzisan was analyzed.Results Fifty-eight active ingredients and 1919 targets of Jinlingzisan were selected from oral bioavailability(OB)and drug-like property(DL);A total of 1420 known disease targets related to neuropathic pain are retrieved by the disease database;Fifty-five core active ingredients and 30 core target proteins were selected out,Molecular docking showed that Quercetin,(S)-Scoulerine and Tetrahydropalmatine might be the key active ingredients;Jinlingzisan mainly affected the signal pathways such as neuroactive ligand-receptor interaction,Calcium signaling pathway and AGE-RAGE signaling pathway.Conclusion Jinlingzisan treats neuropathic pain through its multi-component,multi-target and multi-pathway.