Liu Zhichao, Fu Huanjie, Gan Yongkang, Ye Yujia, Huang Binghui, Jiang Mingxiu, Chen Jinhong, Li Xiaofeng
School of Rehabilitation Medicine, Shandong Second Medical University, Weifang, Shandong, China.
Department of Cardiovascular, Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Pharmacol. 2024 Nov 1;15:1443560. doi: 10.3389/fphar.2024.1443560. eCollection 2024.
This study focused on examining the protection of QiShenYiQi dripping pills (QSYQ) against myocardial infarction (MI) and investigating its potential mechanisms. Ultra high performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was employed to analyze potential active compounds of QSYQ. The targets of these compounds were predicted using an integrated method and cross-referenced with relevant databases to identify associated pathways. Experimental validation was then conducted to confirm the accuracy of the systems pharmacology findings. In the end, network analysis combined with UHPLC screened 13 potential active compounds and obtained 99 targets for the intersection of potential active compounds and diseases. The enrichment analysis results indicated that the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway might be the mechanism of action of QSYQ in the treatment of MI. Experimental verification demonstrated that QSYQ could alleviate oxidative stress, promote vasodilation, and activate proteins related to the mitochondrial ATP-sensitive potassium channel (K) and nitric oxide (NO)-cGMP-PKG signaling pathway. This study provides insights into both the pathogenic mechanisms underlying MI and the molecular mechanisms through which QSYQ may confer protection. Given the role of PKG in regulating myocardial stiffness, it emerges as a promising therapeutic target for myocardial remodeling. We propose that the NO-cGMP-PKG and mitochondrial K pathways may serve as candidate therapeutic targets for the development of new interventions for MI.
本研究聚焦于考察芪参益气滴丸（QSYQ）对心肌梗死（MI）的保护作用，并探究其潜在机制。采用超高效液相色谱- q精确-轨道阱高分辨率质谱（UHPLC-Q-Orbitrap HRMS）分析QSYQ的潜在活性成分。运用综合方法预测这些化合物的靶点，并与相关数据库进行交叉比对以确定相关通路。随后进行实验验证以确认系统药理学研究结果的准确性。最后，网络分析结合UHPLC筛选出13种潜在活性成分，并获得了潜在活性成分与疾病交集的99个靶点。富集分析结果表明，环磷酸鸟苷-蛋白激酶G（cGMP-PKG）信号通路可能是QSYQ治疗MI的作用机制。实验验证表明，QSYQ可减轻氧化应激，促进血管舒张，并激活与线粒体ATP敏感性钾通道（K）和一氧化氮（NO）-cGMP-PKG信号通路相关的蛋白。本研究为MI的发病机制以及QSYQ可能提供保护作用的分子机制提供了见解。鉴于PKG在调节心肌僵硬度中的作用，它成为心肌重塑的一个有前景的治疗靶点。我们提出，NO-cGMP-PKG和线粒体K通道可能作为开发MI新干预措施的候选治疗靶点。
