Liu Mengnan, Yuan Gang, Luo Gang, Guo Xin, Chen Mingtai, Yang Huayi, He Fan, Yang Tingfu, Zhang Xinyue, Wu Qibiao, Zhou Hua, Yang Sijin
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.
Evid Based Complement Alternat Med. 2022 May 2;2022:7578055. doi: 10.1155/2022/7578055. eCollection 2022.
Danshen Decoction comprises , , and . It can promote blood circulation and remove blood stasis, and is commonly used in the treatment of gastric and duodenal ulcers, coronary heart disease, angina pectoris, etc. This research is based on network pharmacology and is experimentally verified to explore the potential mechanism of Danshen Decoction in the treatment of ischemic cardiomyopathy (ICM).
The effective components and targets of Danshen Decoction were firstly extracted from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, the drug-component-target-disease network was then constructed, the protein-protein interaction (PPI) network was constructed, the Gene Ontology (GO) enrichment analysis was carried out, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed in order to find the potential active components and therapeutic mechanisms. Finally, the hypoxia/reoxygenation model in H9c2 cells was established to verify the predicted active components and therapeutic mechanisms.
The results showed that Danshen Decoction has 67 potential active components and 109 therapeutic targets in treating ICM. These targets were rich in a variety of gene functions and different signaling pathways; the main gene targets include TP53, c-Jun, and Akt1. Go enrichment analysis showed that response to drug, membrane raft, and G protein-coupled amine receiver activity rank first in each process, and the main signaling pathways include PI3K-Akt signaling pathway. Through molecular docking and experimental verification of the major active components and core therapeutic targets, the active components of Danshen Decoction demonstrated an ability to reduce the cell damage caused by hypoxia/reoxygenation in H9c2 cells by regulating the core therapeutic target including Akt1, c-Jun, and TP53.
Danshen Decoction has the effect of treating ICM in multiple ways, which is consistent with the results of network pharmacology. This laid a foundation for further study in exploring the active principles and pharmacological mechanism of Danshen Decoction.
丹参饮由[具体成分未给出]组成。它能活血化瘀，常用于治疗胃及十二指肠溃疡、冠心病、心绞痛等。本研究基于网络药理学并经实验验证，以探索丹参饮治疗缺血性心肌病（ICM）的潜在机制。
首先从中药系统药理学（TCMSP）数据库及分析平台提取丹参饮的有效成分和靶点，构建药物 - 成分 - 靶点 - 疾病网络，构建蛋白质 - 蛋白质相互作用（PPI）网络，进行基因本体（GO）富集分析，并分析京都基因与基因组百科全书（KEGG）通路，以寻找潜在的活性成分和治疗机制。最后，建立H9c2细胞缺氧/复氧模型，验证预测的活性成分和治疗机制。
结果显示，丹参饮在治疗ICM方面有67种潜在活性成分和109个治疗靶点。这些靶点富含多种基因功能和不同的信号通路；主要基因靶点包括TP53、c - Jun和Aktl。GO富集分析表明，药物反应、膜筏和G蛋白偶联胺受体活性在各过程中排名靠前，主要信号通路包括PI3K - Akt信号通路。通过对主要活性成分和核心治疗靶点的分子对接及实验验证，丹参饮的活性成分通过调节包括Aktl、c - Jun和TP53在内的核心治疗靶点，表现出减少H9c2细胞缺氧/复氧所致细胞损伤的能力。
丹参饮具有多种方式治疗ICM的作用，这与网络药理学结果一致。这为进一步研究丹参饮的活性成分及药理机制奠定了基础。
