Wang Dan, Tian Li, Shi Chang, Wei Yu-Xi, Wang Han, Liu Tian-Tian, Gong Ming, Zhang Yan-Wen, Yu Rong-Guo, Wu Xiao-Hui
College of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
College of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; Department of Pharmacy, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China.
Comput Biol Med. 2020 Jul;122:103825. doi: 10.1016/j.compbiomed.2020.103825. Epub 2020 Jun 13.
Shen Gui capsule (SGC) is a new national drug in China that is widely used in clinical practice and has significant therapeutic effects on coronary heart disease (CHD). However, its active ingredients and mechanism of action for treating coronary heart disease remain unknown. Therefore, the purpose of this paper is to systematically explore the mechanism and efficacy of SGC in the "multicomponent-multitarget- multipathway" treatment for CHD using network pharmacology technology.
The potential active ingredients of SGC were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and screened by pharmacokinetic parameters. Their possible targets were predicted using the TCMSP and DrugBank database. The CHD-related targets were identified from Comparative Toxicogenomics Database (CTD), UniProt, and PharmGKB database. The compound-target-disease network was constructed using Cytoscape for visualization. Additionally, the protein functional annotation and identification of signaling pathways of potential targets were performed by Gene Ontology (GO) and KEGG enrichment analysis using the Metascape platform.
The 61 active ingredients of SGC were found to regulate neuroactive ligand-receptor interaction, fluid shear stress and atherosclerosis, estrogen signaling pathway and other pathways through 62 targets. SGC is involved in regulating the circulatory system, nervous system and immune system and other aspects of the body, and thus plays a significant role in the treatment of CHD and its complications, showing the mechanism of SGC's "multicomponent, multitarget, and multipathway" prevention and treatment of CHD. In addition, three predictive components were first found to have potential biological activity by this method.
The studies we have performed successfully predict the effective components and potential targets of SGC in the prevention and treatment of CHD, which helped to systematically clarify its mechanism of action and provided a direction for future research on the modern mechanism of SGC in the treatment of CHD.
参桂胶囊（SGC）是中国的一种新型国药，在临床实践中广泛应用，对冠心病（CHD）具有显著治疗效果。然而，其治疗冠心病的活性成分及作用机制尚不清楚。因此，本文旨在利用网络药理学技术系统探究参桂胶囊在冠心病“多成分-多靶点-多途径”治疗中的作用机制及疗效。
从中药系统药理学数据库与分析平台（TCMSP）获取参桂胶囊的潜在活性成分，并通过药代动力学参数进行筛选。利用TCMSP和DrugBank数据库预测其可能的靶点。从比较毒理基因组学数据库（CTD）、UniProt和PharmGKB数据库中鉴定冠心病相关靶点。使用Cytoscape构建化合物-靶点-疾病网络以进行可视化。此外，利用Metascape平台通过基因本体（GO）和KEGG富集分析对潜在靶点的蛋白质功能注释及信号通路进行鉴定。
发现参桂胶囊的61种活性成分通过62个靶点调节神经活性配体-受体相互作用、流体剪切力与动脉粥样硬化、雌激素信号通路等途径。参桂胶囊参与调节机体的循环系统、神经系统和免疫系统等多个方面，从而在冠心病及其并发症的治疗中发挥重要作用，展现了参桂胶囊 “多成分、多靶点、多途径” 防治冠心病的机制。此外，通过该方法首次发现三种预测成分具有潜在生物活性。
我们所进行的研究成功预测了参桂胶囊在防治冠心病中的有效成分和潜在靶点，有助于系统阐明其作用机制，为今后参桂胶囊治疗冠心病的现代机制研究提供了方向。
