甘草抗动脉粥样硬化机制的网络药理学研究

利用网络药理学方法探讨甘草在抗动脉粥样硬化中的分子机制。本研究利用中医药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)分析甘草中的有效活性成分,并获得有效成分的作用靶点。通过Cytoscape软件构建可视化靶点互相作用网络,对网络中的关键靶点进行基因本体(GO)富集分析和KEGG通路富集分析。结果显示甘草中40种有效活性成分的预测靶点共97个,47个靶点与动脉粥样硬化(AS)相关,其中18个是血管保护药物和脂质修饰药物的作用靶点,表明甘草可作为调控AS发展的药物。基于97个预测靶点的GO富集分析,发现甘草可参与多种生物学过程,尤其是应对外源性刺激,以及参与细胞凋亡等过程。通过构建甘草靶点与AS疾病靶点相互作用网络(PPI),确定了AKT1、MAPK3、MAPK1、JUN和CASP3等关键靶点,并对关键靶点进行KEGG富集分析,结果表明甘草主要影响调控细胞增殖、生存以及凋亡的细胞信号转导相关通路,并激活先天免疫相关信号通路,调节炎性细胞因子释放,从而发挥抗动脉粥样硬化作用。甘草具有多成分、多靶点、多途径的作用特点,主要通过PI3K-AKT信号途径、MAPK信号途径、NOD样受体信号通路调控细胞增殖和凋亡,同时发挥免疫调控作用,从而影响动脉粥样硬化的发展,由此可见,甘草可作为动脉粥样硬化疾病治疗的候选中草药。

Exploration of the anti-atherosclerosis mechanism of Glycyrrhizae radix by network pharmacology

To explore the mechanism of Glycyrrhizae radix in anti-atherosclerosis based on network pharmacology. The traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) were used to analyze the effective and active compositions in Glycyrrhizae radix and to obtain the targets of the effective and active compositions. Cytoscape is used to build a heterogeneous network of targets. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis of the key targets in the network were performed by WebGestalt database. A total of 97 predicted targets of 40 effective active compositions in Glycyrrhizae radix were analyzed, and 47 targets were related to AS. Among them, 18 were targets for vasoprotective drugs and lipid-modifying drugs, indicating that Glycyrrhizae radix may regulate atherosclerosis development. Based on GO enrichment analysis of 97 predicted targets, we found that Glycyrrhizae radix participated in a variety of biological processes, especially in response to exogenous stimuli and in the process of apoptosis. Then, by analyzing the protein-protein interaction network (PPI) of Glycyrrhizae radix targets and atherosclerosis-related proteins, we identified the hubs, such as AKT1, MAPK3, MAPK1, JUN, CASP3 and so on. KEGG enrichment analysis of the key targets showed that Glycyrrhizae radix plays an anti-atherosclerotic role mainly by affecting the signal transduction pathways which regulate cell proliferation, survival and apoptosis, and activate the innate immune responses to regulate inflammation cytokines releasement. Those results show that Glycyrrhizae radix has characteristics of multi-components, multi-targets and multi-pathways. It mainly regulates cell proliferation and apoptosis through PI3K-AKT signal pathway and MAPK signal pathway. Meanwhile, it also regulates innate immune responses by NOD-like receptor signal pathway. Therefore, Glycyrrhizae radix could affect the development of atherosclerosis and can be used as a candidate Chinese herbal medicine for the treatment of atherosclerosis.