基于网络药理学及分子对接技术探讨脂必泰防治动脉粥样硬化的潜在作用机制

Potential mechanism of Zhibitai Capsules in preventing and treating atherosclerosis based on network pharmacology and molecular docking technology

目的基于网络药理学和分子对接技术,探讨中药脂必泰防治动脉粥样硬化的潜在作用机制。方法使用TCMSP数据库及结合文献,筛选脂必泰中各味药材的主要活性成分并预测其靶点。通过Genecards、OMIM、Drugbank、DisGENET数据库分别检索动脉粥样硬化的疾病基因,获取脂必泰活性成分与动脉粥样硬化的交集靶点并构建“成分-交集靶点”网络图。利用GO和KEGG数据库对交集靶点进行富集分析,最后通过分子对接技术进行验证。结果脂必泰中4味中药的主要有效成分包括槲皮素、木犀草素、熊果酸、豆甾醇、异鼠里素、表儿茶素、山奈酚;核心交集靶点为白介素-6(IL-6)、丝威原活化蛋白酸酶1(MAPK1)、信号转导和转录激活因子(STAT3)、肿瘤坏死因子(TNF)、核转录因子p65(RELA)等。GO及KEGG富集分析显示,潜在治疗靶点主要与信号受体激活物活性、DNA结合转录因子、受体配体活动有关,涉及晚期糖基化终产物及其受体、磷脂酰肌醇3激酶/蛋白激酶B、白介素-17、肿瘤坏死因子等信号通路。分子对接结果显示,木犀草素与MAPK1的结合活性最好。结论脂必泰通过多成分多靶点,调节炎症、脂质代谢、免疫等多条通路,发挥防治动脉粥样硬化的作用。

Objective To investigate the potential mechanism of Zhibitai Capsules in preventing and treating atherosclerosis(AS)based on network pharmacology and molecular docking technology.Methods The main active components were screened in Zhibitai Capsules and their targets were predicted through TCMSP database combined with literature.AS genes were retrieved from databases of Genecards,OMIM,Drugbank and DisGENET respectively for collecting intersection targets of active components in Zhibitai Capsules and AS to construct a componentintersection targets network planning.The intersection targets were given an enrich analysis by using databases of GO and KEGG,and finally verified by molecular docking technology.Results The main active components of 4 Chinese herbs in Zhibitai Capsules included quercetin,luteolin,ursolic acid,stigmasterol,isorhumin,epicatechin and kaempferol.The core intersection targets included interleukin-6(IL-6),mitogen-activated protein kinases 1(MAPK1),signal transducer and activator of transcription 3(STAT3),tumor necrosis factor(TNF)and nuclear factor NF-kappa-B p65 subunit(RELA).The results of enrichment analyses of GO and KEGG showed that potential therapeutic targets were correlated to activity of signal receptor activators,DNA-binding transcription factors and receptor ligands,and involved in advanced glycation end products(AGEs)and their receptors,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),IL-17,TNF and other signaling pathways.The results of molecular docking showed that the binding activity was the best between luteolin and MAPK1.Conclusion Zhibitai Capsules plays a role in preventing and treating AS through regulating inflammation,lipid metabolism,immunity and other pathways based on multi-components and multi-targets.