基于网络药理学和分子对接技术研究抗601合剂的抗病毒抗炎作用机制

Antiviral and anti-inflammatory mechanism of Anti-601 Mixture based on network pharmacology and molecular docking

通过网络药理学和分子对接技术研究中药复方制剂抗601合剂抗病毒抗炎的潜在作用机制。借助中药系统药理学数据库和分析平台(TCMSP)检索抗601合剂中的黄芪、黄柏、大黄、板蓝根、金银花的化学成分和作用靶点。通过UniProt数据库查询靶点对应的基因,进而运用Cytoscape 3.7.2建立药材-化合物-靶点(基因)网络,再通过Webgestalt行功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,预测其抗病毒、抗炎作用机制。药材-化合物-靶点(基因)网络包含药材5个、化合物100个、靶点207个。功能富集分析得到基因本体(GO)条目717个(P≤0.05),其中生物过程(BP)条目240个,细胞组成(CC)条目240个,分子功能(MF)条目237个。KEGG通路富集筛选得到209条信号通路(P≤0.05)。分子对接技术显示抗601合剂的活性成分豆甾醇、槲皮素、木犀草素、刺槐黄素、β-谷甾醇、山柰酚等与前列腺素内过氧化物合酶2(PTGS2)靶点的亲和力较强,可能通过PTGS2靶点调控晚期糖基化终产物及其受体(AGE-RAGE)信号通路、IL-17信号通路、肿瘤坏死因子(TNF)信号通路等多种通路,从而发挥抗病毒、抗炎作用。

The potential antiviral and anti-inflammatory mechanism of Anti-601 Mixture,a traditional Chinese medicine compound preparation,was studied by network pharmacology and molecular docking.The chemical constituents and targets of astragali radix,phellodendri chinensis cortex,rhei radix et rhizome,isatidis radix and lonicerae japonicae flos in Anti-601 Mixture were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The genes corresponding to the target were searched through the UniProt database,and the drug-compound-target(gene)network was constructed by Cytoscape 3.7.2.Then the functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted through Webgestalt to predict the mechanism.The network of drug-compound-target(gene)contained 5 drugs,100 compounds and 207 targets.Functional enrichment analysis resulted in 717 GO items(P≤0.05),among which 240 were biological process(BP)items,240 were cell composition(CC)items,and 237 were molecular function(MF)items.The 209 signaling pathways were obtained by enrichment screening of KEGG pathway(P≤0.05).Molecular docking showed that the active ingredients of Anti-601 Mixture,such as Stigmasterol,quercetin,luteolin,acacetin,β-sitosterol,kaempferol,had strong affinity with PTGS2 target.Active compounds in Anti-601 Mixture may regulate multiple signaling pathways including advanced glycation end products and its receptor(AGE-RAGE),IL-17,tumor necrosis factor(TNF)through target of prostaglandin-endoperoxidase synthase 2(PTGS2),thus playing an antiviral and anti-inflammatory role.