基于网络药理学探讨山楂叶抗高脂血症作用机制及其分子对接验证

A study on the action mechanism of Shanzha leaf on hyperlipidemia based on network pharmacology and its molecular docking verification

目的:基于网络药理学,采用数据挖掘的方法分析山楂叶治疗高脂血症的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)获得中药山楂叶的有效成分及其靶点;运用GeneGards和OMIM筛选与高脂血症相关的基因靶点,构建山楂叶与高脂血症靶点的交集,获得作用靶点;构建药物-有效成分-疾病-靶点网络和蛋白质-蛋白质相互作用网络。进一步分析靶点对应的生物作用、疾病及相关的信号通路,阐述山楂叶治疗高脂血症的作用机制。结果:共筛选出山楂叶作用于高脂血症的有效成分6个,分别为异鼠李素、槲皮素、山柰酚、豆甾醇、谷甾醇、表儿茶素等。获得蛋白质-蛋白质相互作用核心靶点有白细胞介素(Interleukin,IL)-6、过氧化物酶体增生激活受体γ(Peroxisome Proliferative Activated Receptorγ,PPARG)、胱冬酶(Caspase,CASP)3等共54个,涉及基因本体论(GO)生物学功能81个;治疗高脂血症的作用机制与153条通路相关,主要涉及脂质和动脉粥样硬化、晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Receptor For Advanced Glycation End Products,RAGE)信号通路以及磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路等。结论:网络药理学研究表明山楂叶通过重要靶点和多个信号通路有效治疗高脂血症。

Objective:To analyze the effect mechanism of Shanzha(Fructus crataegi)leaf on hyperlipidemia by data mining based on network pharmacology.Methods:The effective components and their targets of Shanzha leaf were obtained by TCMSP data platform.Gene targets related to hyperlipidemia were screened by GeneGards and OMIM database,and the intersection of Shanzha leaf and hyperlipidemia target was constructed to obtain the targets.The drug-active component-disease-target network and protein-protein interaction network were constructed.The biological effects,diseases and related signal pathways corresponding to the target were further analyzed,and the action mechanism of Shanzha leaf on hyperlipidemia was expounded.Results:A total of 6 effective components of Shanzha leaf on hyperlipidemia were screened out,including isorhamnetin,quercetin,kaempferol,stigmasterol,sitosterol and epicatechin.PPI core targets included IL-6,PPARG and CASP3,with 81 of which were related to the biological function of GO.The mechanism of action for hyperlipidemia was associated with 153 pathways,mainly involved lipid and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and PI3K-Akt signaling pathway.Conclusion:This network pharmacology research shows that Shanzha leaf can effectively treat hyperlipidemia through important targets and multiple signaling pathways.