基于网络药理学和分子对接探究花椒叶抗动脉粥样硬化的作用机制

Anti-atherosclerosis Mechanisms of Zanthoxylum Bungeanum Maxim.Leaves Based on Network Pharmacology and Molecular Docking

借助网络药理学探究花椒叶抗动脉粥样硬化的潜在活性成分和作用机制,并用分子对接与细胞实验进行验证。通过查阅文献收集花椒叶化学成分,借助Swiss Target Prediction对花椒叶活性成分和相关靶点进行筛选;利用Gene Cards、OMIM数据库检索与动脉粥样硬化疾病相关的靶点;绘制花椒叶抗动脉粥样硬化的蛋白-蛋白相互作用网络,进一步借助David数据库进行通路富集分析;对关键靶点进行分子对接验证;最后,用脂多糖刺激的RAW264.7细胞验证关键成分的抗炎作用。结果表明,筛选得到花椒叶活性成分168个,花椒叶抗动脉粥样硬化的潜在靶点131个,蛋白-蛋白相互作用分析得到的关键靶点有TNF、IL6、AKT等,KEGG富集显示参与的信号通路有AGE-RAGE信号通路、VEGF信号通路、HIF-1信号通路等。分子对接结果显示,关键靶点与关键成分有较好的结合性。抗炎实验结果显示,花椒叶关键成分可以有效抑制脂多糖刺激的RAW264.7细胞中NO的产生。为花椒叶抗动脉粥样硬化研究提供了理论依据,为花椒叶的开发利用提供了有益探索。

The potential active components and anti-atherosclerosi mechanisms of Z.bungeanum Maxim.leaves are investigated by means of network pharmacology,and verified by molecular docking and cell experiments.The chemical components of Z.bungeanum Maxim.leaves are collected by referring to literatures,and the active components and related targets are screened by Swiss Target Prediction.Genecards and OMIM databases are used to search the targets related to atherosclerosis.The protein-protein interaction network of Z.bungeanum Maxim.leaves against atherosclerosis is mapped,and pathway enrichment analysis is conducted with David database.The key components and targets are verified by molecular docking.Finally,the anti-inflammatory effects of key components are verified on lipopolysaccharide stimulated RAW264.7 cells.The results show that 168 active components and 131 potential anti-atherosclerosis targets of Z.bungeanum Maxim.leaves are screened,and the key targets are obtained by PPI analysis,including TNF,IL6 and AKT,etc.KEGG enrichment results show that the signaling pathways,ie AGE-RAGE,VEGF,HIF-1 signaling pathways,involved in the regulation.The results of molecular docking of key components and targets show a good bonding.The results of anti-inflammatory experiment show that the key components of Z.bungeanum Maxim.leaves can effectively inhibit the production of NO in lipopolysaccharide stimulated RAW264.7 cells.This study provides theoretical basis for the investigation of anti-atherosclerosis effect of Z.bungeanum Maxim.leaves and beneficial exploration for the development and utilization of Z.bungeanum Maxim.Leaves.