Abstract:

Objective　To investigate the mechanism of Xinkeshu in the treatment of coronary heart disease (CHD) based on network pharmacology and molecular docking technology. Methods　The active components and targets of Xinkeshu were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and HERB databases. The OMIM and GeneCards databases were used to acquire targets related to CHD. Time: Unlimited-December 2024. The common targets of drugs and diseases were obtained by drawing Venn diagram. The common targets were imported into the STRING database for protein interrelationship analysis. The Cytoscape 3.10.2 was applied to construct the protein-protein interaction (PPI) network and the "Chinese medicine-active component-target" network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed via the DAVID database. The key active components and core targets screened from the network data were validated using AutoDock Tools for molecular docking. Results　Through the screening process, 77 main active components and 378 targets were identified for Xinkeshu, with 194 common targets shared between Xinkeshu and CHD. Following molecular docking validation, the core targets determined were interleukin-6 (IL-6), serine/threonine protein kinase B (AKT1), tumor necrosis factor (TNF), tumor protein p53 (TP53), cysteine aspartate protease 3 (CASP3), and epidermal growth factor receptor (EGFR). The key active components included β-sitosterol, luteolin, formononetin, Stigmasterol, 1,2,5,6-tetrahydrotanshinone, and DFV. GO and KEGG enrichment analysis suggested that the core targets were primarily enriched in pathways regulating lipid metabolism and atherosclerosis, AGE/RAGE signaling pathway, PI3K-AKT signaling pathway, fluid shear stress, and insulin resistance. These pathways were involved in biological processes such as response to external stimuli, positive regulation of cell migration, phosphorylation, negative regulation of apoptotic process, and positive regulation of the ERK1 and ERK2 cascade. Conclusion　The main active components of Xinkeshu may treat CHD by regulating core targets such as IL-6, AKT1, TNF, and multiple pathways including lipid metabolism and atherosclerosis, the AGE/RAGE signaling pathway, and the PI3K-Akt signaling pathway. These effects are likely achieved through anti-inflammatory actions, regulation of cell proliferation, and apoptosis.

Key words:

 , Coronary heart disease, Xinkeshu, Network pharmacology, Molecular docking, Action mechanism

摘要：

目的　通过网络药理学和分子对接技术探讨心可舒治疗冠心病的物质基础和作用机制。方法　通过中药系统药理学数据库与分析平台（TCMSP）、HERB数据库获得心可舒的有效活性成分及靶点；运用OMIM与GeneCards数据库获取冠心病相关靶点。时间：不限—2024年12月。通过绘制维恩图得到药物与疾病的共同靶点，将共同靶点导入STRING数据库进行蛋白质-蛋白质相互作用（PPI）关系分析，应用Cytoscape 3.10.2构建PPI网络及中药-活性成分-靶点网络，通过DAVID数据库进行基因本体（GO）、京都基因和基因组百科全书（KEGG）富集分析，筛选得到的关键活性成分及核心靶点使用AutoDock Tools进行分子对接验证。结果　筛选得到心可舒77个主要活性成分、378个作用靶点，194个心可舒与冠心病共同靶点。经分子对接验证后，得到排名前6位的核心靶点分别为白细胞介素-6（IL-6）、丝氨酸/苏氨酸蛋白激酶B（AKT1）、肿瘤坏死因子（TNF）、肿瘤蛋白p53（TP53）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、表皮生长因子受体（EGFR），排名前6位的心可舒关键活性成分为β-谷甾醇、木犀草素、芒柄花黄素、豆甾醇、四氢丹参酮Ⅰ、甘草素。GO与KEGG富集分析结果显示，核心靶点主要富集在调控脂质代谢与动脉粥样硬化、晚期糖基化终末产物（AGE）/糖基化终末产物受体（RAGE）信号通路、磷脂酰肌醇3-激酶（PI3K）-蛋白激酶B（Akt）信号通路、流体剪切应力及胰岛素抵抗等信号通路，涉及外源刺激反应、细胞群增殖的正调控、磷酸化、凋亡过程的负调控、ERK1和ERK2级联的正调控等生物过程。结论　心可舒的关键活性成分可能是通过调节IL-6、AKT1、TNF等核心靶点，涉及脂质代谢与动脉粥样硬化、AGE/RAGE信号通路、PI3K/Akt信号通路等多条通路，通过抗炎、调控细胞增殖及凋亡等机制治疗冠心病。

关键词:

冠心病, 心可舒, 网络药理学, 分子对接, 作用机制