畅脉乐I号胶囊治疗动脉粥样硬化的网络药理学作用机制
Network Pharmacological Mechanism of Chang Mai-Le I Capsule in the Treatment of Atherosclerosis

【目的】应用网络药理学的方法探讨畅脉乐I号胶囊(CML)治疗动脉粥样硬化(AS)的作用机制。【方法】通过TCMSP、Genecards、OMIM和DisGeNET数据库结合文献检索获取CML活性成分与靶点及疾病相关靶点，经Uniprot数据库对选取靶点标准化后利用jvenn筛选成分基因与疾病基因的交集基因，导入Cytoscape3.8.2软件构建活性成分–疾病靶点网络与靶点间蛋白–蛋白相互作用(PPI)网络；通过Metascape平台对交集基因进行基因本体(GO)富集分析以及京都基因和基因组百科全书(KEGG)通路富集分析。【结果】筛选出CML活性成分116个活性成分及480个成分靶点，AS疾病靶点2358个，主要活性成分为槲皮素、白藜芦醇、刺芒柄花素、木犀草素、异鼠李素、黄芩素、丹参酮II等。将药物靶点与疾病靶点取交集共得到182个交集基因，用交集基因构建PPI网络。这些基因主要与细胞对脂质的反应、对氧气水平的反应、对细胞因子的反应等生物进程有关，它们的分子功能主要与激酶结合、DNA结合转录因子结合、蛋白质同二聚化活性、蛋白质结构域特异性结合等相关，主要富集在膜筏、转录调节复合物、受体复合物等部位。【结论】CML通过多成分、多靶点以及多途径参与防治AS过程，其药效物质AGE-RAGE信号通路、FoxO信号通路、NF-κB信号通路、JAK-STAT信号通路等发挥效应，以上数据为CML进一步的临床应用及基础研究提供参考依据。
Objective: To apply the method of network pharmacology to explore the mechanism of Chang Mai-Le I Capsule (CML) in the treatment of atherosclerosis (AS). Methods: The active ingredient-target and disease-related targets of CML were obtained through TCMSP, Genecards, OMIM and DisGeNET databases combined with literature search, and the selected targets were standardized by Uniprot database and then screened by jvenn for the intersection of ingredient genes and disease genes, and imported into Cytoscape 3.8.2 software to construct the active ingredient-disease target network and target network. The intersecting genes were enriched for gene ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) pathways through the Metascape platform. Results: The 116 active ingredients and 480 component targets of CML were screened, and 2358 AS disease targets were identified, with the main active ingredients being quercetin, resveratrol, prickly mangosteen, lignan, isorhamnetin, baicalin and tanshinone II. A total of 182 intersecting genes were obtained by taking the intersection of drug targets and disease targets, and the intersecting genes were used to construct the PPI network. These genes were mainly related to biological processes such as cellular responses to lipids, responses to oxygen levels, and responses to cytokines. Their molecular functions were mainly related to kinase binding, DNA-binding transcription factor binding, protein homodimerization activity, and protein structural domain-specific binding, and were mainly enriched in sites such as membrane rafts, transcriptional regulatory complexes, and receptor complexes. Conclusion: CML is involved in the prevention and treatment of AS through multiple components, multiple targets and multiple pathways, and its pharmacological substances AGE-RAGE signaling pathway, FoxO signaling pathway, NF-κB signaling pathway and JAK-STAT signaling pathway exert effects. The above data provide a