Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
Immunology Research Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
Biomed Pharmacother. 2020 Jan;121:109655. doi: 10.1016/j.biopha.2019.109655. Epub 2019 Nov 14.
Coronary heart disease (CHD) is a leading cause of death and disability worldwide. Huoxue Anxin Recipe (HAR) is a novel Chinese Herbal Medicine formula of that has been used to treat CHD for several decades. Our previous study found that HAR had anti-oxidative effects, and could promote myocardial angiogenesis and improve cardiac function following myocardial infarction (MI) in rats. However, the active compounds, potential targets, and biological processes related to HAR have not been systematically investigated. Here, network pharmacology and experimental validation were used to study the protective mechanisms of HAR against CHD. We identified 124 active components, 124 verified targets, and 111 predictive targets. A total of 1192 genes related to CHD were identified by cDNA microarray and database analysis. A total of 47 putative targets of HAR against CHD were identified, including 32 verified targets and 15 predictive targets. ClueGo enrichment analysis identified 49 biological processes involved in the anti-CHD effects of HAR. Among them, the negative regulation of blood coagulation and regulation of collagen biosynthetic process were experimentally validated. After constructing a protein-protein interaction network and clustering with MECODE and ClusterONE, 162 key proteins (from ClueGo and clustering) were used to construct an internal interaction network. Complement C3 (C3), Fibrinogen alpha (FGA), Fibrinogen gamma (FGG), interleukin-6 (IL6), and Apolipoprotein A1 (APOA1) were the top 5 hub proteins identified by cytoHubber analysis. HAR limited the concentrations of C3, FGA, FGG, and IL6 and increased APOA1 levels. The results indicated that HAR could down-regulate blood coagulation, regulate collagen biosynthesis, inhibit peroxidation and inflammation injury, and promote cholesterol efflux. HAR could be a potential source of novel and effective drugs for CHD.
冠心病（CHD）是全球范围内主要的死亡和残疾原因。活血安心方（HAR）是一种新型中药方剂，已用于治疗 CHD 数十年。我们之前的研究发现，HAR 具有抗氧化作用，可促进心肌梗死后大鼠的心肌血管生成和改善心功能。然而，HAR 的活性化合物、潜在靶点和与 HAR 相关的生物学过程尚未得到系统研究。在这里，我们采用网络药理学和实验验证的方法研究了 HAR 对 CHD 的保护机制。我们鉴定了 124 种活性成分、124 个验证靶点和 111 个预测靶点。通过 cDNA 微阵列和数据库分析共鉴定出 1192 个与 CHD 相关的基因。共鉴定出 HAR 治疗 CHD 的 47 个潜在靶点，包括 32 个验证靶点和 15 个预测靶点。ClueGO 富集分析确定了 HAR 抗 CHD 作用涉及的 49 个生物学过程。其中，血液凝固的负调控和胶原生物合成过程的调控得到了实验验证。在构建蛋白质-蛋白质相互作用网络并使用 MECODE 和 ClusterONE 聚类后，使用 162 个关键蛋白（来自 ClueGO 和聚类）构建了内部相互作用网络。CytoHubber 分析鉴定出 5 个关键蛋白，分别是补体 C3（C3）、纤维蛋白原α（FGA）、纤维蛋白原γ（FGG）、白细胞介素 6（IL6）和载脂蛋白 A1（APOA1）。HAR 限制了 C3、FGA、FGG 和 IL6 的浓度，增加了 APOA1 的水平。结果表明，HAR 可下调血液凝固、调节胶原生物合成、抑制过氧化和炎症损伤、促进胆固醇外排。HAR 可能是 CHD 的新型有效药物的潜在来源。
