Department of College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China.
Department of College of Pharmacy, Xi'an Jiao Tong University, Xi'an, Shaanxi, 710049, China.
Biomed Pharmacother. 2019 Oct;118:109234. doi: 10.1016/j.biopha.2019.109234. Epub 2019 Aug 1.
Compound Longmaining (CLMN) decoction, a herbal formula from Traditional Chinese Medicine (TCM), has been widely used for the treatment of cardiovascular diseases, especially myocardial infarction (MI) in recent years. With limited knowledge of mechanisms underlying the therapeutic effect of CLMN on MI, this study was to use Network Pharmacology-based approach together with mice MI model to gain more insight of such mechanisms. The outcomes showed that 37 active compounds were identified constituting CLMN and targeting 444 genes, which were cross-referenced with MI associated genes, leading to identification of 24 target genes of CLMN for MI. Gene Ontology (GO) enrichment analysis of the 24 target genes was performed with 53 entries, amongst which include extracellular matrix decomposition, protein hydrolysis, cellular protein metabolism, protein hydrolysis, receptor binding, and NAD binding. There were 14 pathways generated using KEGG enrichment (p < 0.05). The constructed medicinal material-chemical component-target-pathway network identified seven core target with relatively higher values of degree and betweenness. in vivo experiments, where the effects of CLMN was examined on mice model of MI, confirmed that CLMN could protect myocardium by regulating these targets. The therapeutic effect of CLMN on MI is due to its effect in delaying ventricular remodeling, reducing myocardial fibrosis and apoptosis after MI, which can protect myocardial tissue.
复方龙牡(CLMN)汤是一种来自中药(TCM)的草药配方,近年来已广泛用于治疗心血管疾病,特别是心肌梗死(MI)。由于对 CLMN 对 MI 的治疗作用机制知之甚少,本研究采用基于网络药理学的方法结合 MI 小鼠模型,以更深入地了解这些机制。研究结果表明,鉴定出 37 种构成 CLMN 的活性化合物,靶向 444 个基因,这些基因与 MI 相关基因交叉参照,确定了 CLMN 治疗 MI 的 24 个靶基因。对 24 个 CLMN 靶基因进行基因本体(GO)富集分析,共得到 53 个条目,其中包括细胞外基质分解、蛋白水解、细胞蛋白代谢、蛋白水解、受体结合和 NAD 结合。通过 KEGG 富集分析得到 14 条通路(p<0.05)。构建的中药-化学成分-靶标-通路网络,确定了七个核心靶标,它们的度和介数值相对较高。体内实验中,观察了 CLMN 对 MI 小鼠模型的作用,证实 CLMN 可以通过调节这些靶标来保护心肌。CLMN 对 MI 的治疗作用是由于其在延迟心室重构、减少 MI 后心肌纤维化和细胞凋亡方面的作用,从而保护心肌组织。