Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
Medicine (Baltimore). 2022 Jul 8;101(27):e29829. doi: 10.1097/MD.0000000000029829.
Coronary artery disease (CAD) is a cardiovascular disease characterized by atherosclerosis, angiogenesis, thrombogenesis, inflammation, etc. Xintong granule (XTG) is considered a practical therapeutic strategy in China for CAD. Although its therapeutic role in CAD has been reported, the molecular mechanisms of XTG in CAD have not yet been explored. A network pharmacology approach including drug-likeness (DL) evaluation, oral bioavailability (OB) prediction, protein-protein interaction (PPI) network construction and analysis, and Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses was used to predict the active ingredients, potential targets, and molecular mechanisms of XTG associated with the treatment of CAD. Molecular docking analysis was performed to investigate the interactions between the active compounds and the underlying targets. Fifty-one active ingredients of XTG and 294 CAD-related targets were screened for analysis. Gene Ontology enrichment analysis showed that the therapeutic targets of XTG in CAD are mainly involved in blood circulation and vascular regulation. KEGG pathway analysis indicated that XTG intervenes in CAD mainly through the regulation of fluid shear stress and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. Molecular docking analysis showed that each key active ingredient (quercetin, luteolin, kaempferol, stigmasterol, resveratrol, fisetin, gamma-sitosterol, and beta-sitosterol) of XTG can bind to the core targets of CAD (AKT1, JUN, RELA, MAPK8, NFKB1, EDN1, and NOS3). The present study revealed the CAD treatment-related active ingredients, underlying targets, and potential molecular mechanisms of XTG acting by regulating fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and relaxin signaling pathway.
冠状动脉疾病 (CAD) 是一种心血管疾病，其特征为动脉粥样硬化、血管生成、血栓形成、炎症等。心通颗粒 (XTG) 被认为是中国 CAD 的一种实用治疗策略。虽然已经报道了其在 CAD 中的治疗作用，但 XTG 在 CAD 中的分子机制尚未得到探索。采用包括药物相似性 (DL) 评估、口服生物利用度 (OB) 预测、蛋白质-蛋白质相互作用 (PPI) 网络构建和分析以及基因本体论术语和京都基因与基因组百科全书 (KEGG) 通路分析的网络药理学方法，预测 XTG 治疗 CAD 的活性成分、潜在靶点和分子机制。进行分子对接分析以研究活性化合物与潜在靶点之间的相互作用。筛选出 XTG 的 51 种活性成分和 294 种 CAD 相关靶点进行分析。基因本体论富集分析表明，XTG 在 CAD 中的治疗靶点主要涉及血液循环和血管调节。KEGG 通路分析表明，XTG 主要通过调节流体切应力和动脉粥样硬化、糖尿病并发症中的 AGE-RAGE 信号通路以及松弛素信号通路来干预 CAD。分子对接分析表明，XTG 的每个关键活性成分（槲皮素、木樨草素、山奈酚、豆甾醇、白藜芦醇、漆黄素、γ-谷甾醇和β-谷甾醇）都可以与 CAD 的核心靶点（AKT1、JUN、RELA、MAPK8、NFKB1、EDN1 和 NOS3）结合。本研究揭示了 XTG 通过调节流体切应力和动脉粥样硬化、糖尿病并发症中的 AGE-RAGE 信号通路以及松弛素信号通路，治疗 CAD 的相关活性成分、潜在靶点和潜在分子机制。
