基于网络药理学和分子对接技术研究花生红衣多酚抗动脉粥样硬化的作用机制

Study on anti-atherosclerosis mechanism of action of peanut skin polyphenols based on network pharmacology and molecular docking

为研究花生红衣多酚抗动脉粥样硬化的作用机制,该研究利用网络药理学和分子对接技术进行了活性成分、靶点及通路预测。通过TCMSP平台和文献搜索获得花生红衣多酚的活性成分,利用相关数据库获得花生红衣多酚活性成分和动脉粥样硬化的相关靶点;采用DAVID平台进行GO和KEGG富集分析,并通过Cytoscape软件,构建“花生红衣酚类活性成分-作用靶点-通路”网络图;最后,采用AutoDockTools软件对活性成分与核心靶点进行分子对接。筛选得到山奈酚、表儿茶素、漆黄素、儿茶素、木犀草素、槲皮素、原花青素B1、表没食子儿茶素没食子酸酯等13个花生红衣多酚活性成分和丝氨酸/苏氨酸激酶1、磷脂酰肌醇-3-激酶调节亚基1、丝裂原活化蛋白激酶1、表皮生长因子受体(epithelial growth factor receptor,EGFR)、肿瘤蛋白p53等65个核心靶点。花生红衣多酚发挥抗动脉粥样硬化作用主要涉及磷脂酰肌醇3-激酶/蛋白激酶B信号通路信号、脂质与动脉粥样硬化、流体剪切应力和动脉粥样硬化、白细胞介素-17信号通路和EGFR酪氨酸激酶抑制剂通路。分子对接结果表明,花生红衣多酚的主要活性成分与关键靶点均能稳定结合。花生红衣多酚通过多成分、多靶点、多通路干预脂质代谢、炎症、细胞增殖和凋亡等多个生理过程而发挥抗动脉粥样硬化作用,从而为花生红衣抗动脉粥样硬化功能健康食品的开发利用提供理论依据。

To study the anti-atherosclerosis mechanism of action of peanut skin polyphenols,network pharmacology and molecular docking techniques were used to predict the active components,targets,and pathways.The active components of peanut skin polyphenols were obtained through the TCMSP platform and literature search,and the related targets of peanut skin polyphenols and atherosclerosis were obtained by using the relevant databases.GO and KEGG enrichment analyses were performed by the DAVID database.The“active components of peanut skin polyphenols-target-pathway”interaction network was constructed by Cytoscape software.Finally,molecular docking of active ingredients and the core target were performed using AutoDockTools software.Results showed that 13 active components of peanut skin polyphenols such as kaempferol,epicatechin,fisetin,catechin,luteolin,quercetin,procyanidin B1,and epigallocatechin gallate were screened.And 65 key targets such as alpha serine/threonine-protein kinase(AKT1),phosphatidylinositol 3-kinase regulatory subunit 1(PIK3R1),mitogen-activated protein kinase-1(MAPK1),epithelial growth factor receptor(EGFR),and tumor protein p53(TP53)were obtained.The peanut skin polyphenols played an anti-atherosclerosis effect,mainly involving the phosphatidylinositol-3-kinase(PI3K)-protein kinase B(Akt)signaling pathway,lipid and atherosclerosis,fluid shear stress and atherosclerosis,interleukin-17(IL-17)signaling pathway,and EGFR tyrosine kinase inhibitor resistance.The results of molecular docking showed that the main active components could be stably combined with key targets.Peanut skin polyphenols could against atherosclerosis through collaborative intervention in physiological processes through multiple components,multiple targets,and multiple pathways.The physiological processes mainly included lipid metabolism,inflammation,and cell proliferation and apoptosis.The result provided a theoretical basis for the development of anti-atherosclerosis functional food with peanut skin.