基于网络药理学和分子对接研究牡丹皮-丹参药对治疗银屑病的作用机制

Mechanism of Cortex Moutan-Salviae Miltiorrhizae in the Treatment of Psoriasis Based on Network Pharmacology and Molecular Docking Technology

目的:本文借助计算机网络药理学和分子对接技术预测牡丹皮、丹参治疗银屑病的潜在分子作用机制。方法:首先将中药系统药理学数据库与分析平台(TCMSP)、GeneCards、在线人类孟德尔遗传数据库(OMIM)平台筛选到的疾病和药对成分靶点取交集,获得交集靶点后进行基因本体(GO)、京都基因和基因组百科全书(KEGG)富集分析,利用Cytoscape 3.8.2构建蛋白质-蛋白质相互作用(PPI)网络和“成分-靶点-通路”图,最后使用Schrodinger Maestro 11.8进行分子对接试验。结果:共得到牡丹皮、丹参治疗银屑病的活性成分58个和靶点95个,主要参与脂多糖应答、炎症反应、营养水平、氧化应激等方面的生物过程,调控白细胞介素-17(IL-17)、肿瘤坏死因子(TNF)、辅助性T17(Th17)细胞分化、缺氧诱导因子-1(HIF-1)等信号通路。分子对接结果证实主要活性成分和核心靶点亲和力高。结论:牡丹皮-丹参配伍可从多成分、多靶点、多通路治疗银屑病。

Objective:This study used computer network pharmacology and molecular docking technology to predict the potential molecular mechanism of Cortex Moutan and Salviae Miltiorrhizae in the treatment of psoriasis.Methods:Firstly,the targets of diseases and ingredients screened by TCMSP,GeneCards and OMIM platforms were intersected.After obtaining the intersection targets,GO and KEGG enrichment analyses were performed.Cytoscape 3.8.2 was applied to construct the PPI network and“ingredient-target-pathway”network diagram.Finally,the molecular docking test was performed using Schrodinger Maestro 11.8.Results:A total of 58 active ingredients and 95 targets of Cortex Moutan and Salviae Miltiorrhizae in the treatment of psoriasis were obtained.They mainly involved in such biological processes as lipopolysaccharide response,inflammation reaction,nutrient levels,and oxidative stress,and regulated such signaling pathways as IL-17,TNF,Th17 cell differentiation,and HIF-1.The results of molecular docking technology confirmed a high affinity between main active ingredients and core targets.Conclusion:Cortex Moutan-Salviae Miltiorrhizae may be used to treat psoriasis through multiple components,multiple targets,and multiple pathways.