Mao Qianping, Shao Chongyu, Zhou Huifen, Yu Li, Bao Yida, Zhao Yali, Yang Jiehong, Wan Haitong
School of Life Sciences, Zhejiang Chinese Medicine University, Hangzhou 310053, China.
School of Basic Medicine, Zhejiang Chinese Medicine University, Hangzhou 310053, China.
Pharmaceuticals (Basel). 2024 Feb 28;17(3):309. doi: 10.3390/ph17030309.
This study aimed to explore the mechanisms through which salvianolic acid B (Sal-B) exerts its effects during myocardial ischemia-reperfusion injury (MI/RI), aiming to demonstrate the potential pharmacological characteristics of Sal-B in the management of coronary heart disease. First, Sal-B-related targets and MI/RI-related genes were compiled from public databases. Subsequent functional enrichment analyses using the protein-protein interaction (PPI) network, gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) predicted the core targets and approaches by which Sal-B counters MI/RI. Second, a Sal-B-treated MI/RI mouse model and oxygen-glucose deprivation/reoxygenation (OGD/R) H9C2 cell model were selected to verify the main targets of the network pharmacological prediction. An intersectional analysis between Sal-B and MI/RI targets identified 69 common targets, with a PPI network analysis highlighting caspase-3, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) as central targets. GO and KEGG enrichment analyses indicated remarkable enrichment of the apoptosis pathway among these targets, suggesting their utility in experimental studies in vivo. Experimental results demonstrated that Sal-B treatment not only mitigated myocardial infarction size following MI/RI injury in mice but also modulated the expression of key apoptotic regulators, including Bcl-2-Associated X (Bax), caspase-3, JNK, and p38, alongside enhancing the B-cell lymphoma-2 (Bcl-2) expression, thereby inhibiting myocardial tissue apoptosis. This study leveraged an integrative network pharmacology approach to predict Sal-B's potential targets in MI/RI treatment and verified the involvement of key target proteins within the predicted signaling pathways through both in vivo and in vitro experiments, offering a comprehensive insight into Sal-B's pharmacological mechanism in MI/RI management.
本研究旨在探讨丹酚酸B（Sal-B）在心肌缺血再灌注损伤（MI/RI）过程中发挥作用的机制，以阐明Sal-B在冠心病治疗中的潜在药理特性。首先，从公共数据库中收集Sal-B相关靶点和MI/RI相关基因。随后，利用蛋白质-蛋白质相互作用（PPI）网络、基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行功能富集分析，预测Sal-B对抗MI/RI的核心靶点和途径。其次，选择Sal-B处理的MI/RI小鼠模型和氧糖剥夺/复氧（OGD/R）H9C2细胞模型来验证网络药理学预测的主要靶点。Sal-B与MI/RI靶点的交集分析确定了69个共同靶点，PPI网络分析突出显示半胱天冬酶-3、c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶（p38）为核心靶点。GO和KEGG富集分析表明这些靶点中凋亡途径显著富集，表明它们在体内实验研究中的实用性。实验结果表明，Sal-B处理不仅减轻了小鼠MI/RI损伤后的心肌梗死面积，还调节了关键凋亡调节因子的表达，包括Bcl-2相关X蛋白（Bax）、半胱天冬酶-3、JNK和p38，同时增强了B细胞淋巴瘤-2（Bcl-2）的表达，从而抑制心肌组织凋亡。本研究利用综合网络药理学方法预测Sal-B在MI/RI治疗中的潜在靶点，并通过体内和体外实验验证了预测信号通路中关键靶蛋白的参与，全面深入地了解了Sal-B在MI/RI管理中的药理机制。
