Liu Chunhua, He Yu, Wang Mingjin, Sun Jia, Pan Jie, Liu Ting, Li Yueting, Zhou Meng, Huang Yong, Li Yongjun, Zhang Yanmin, Lu Yuan
State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, China.
School of Pharmacy, Guizhou Medical University, Guiyang 550025, China.
Pharmaceuticals (Basel). 2024 Sep 27;17(10):1288. doi: 10.3390/ph17101288.
L. (PO) has demonstrated notable efficacy in treating coronary heart disease. Previous research identified eight key active components in PO for cardiomyocyte protection, but the underlying mechanisms remained unclear; Methods: Network pharmacology and molecular docking were used to identify potential target proteins of PO's active components. Experimental models assessed the cardioprotective effects and mechanisms; Results: Network analysis and molecular docking revealed that the active components exhibited the highest binding affinity with SOD2, indicating it as a key element in the cardiac protection of PO. In vivo, PO extract improved myocardial structure and function, and increased SOD2 protein levels. In vitro, the active components of PO (Mixture) mitigated oxidative stress and apoptosis, upregulating SIRT3 and decreasing acetylated SOD2, leading to increased SOD2 and reduced ROS levels. The observed effects were reversed by a SIRT3 inhibitor, indicating the involvement of the SIRT3/SOD2 signaling pathway; Conclusions: This comprehensive approach elucidated the critical mechanisms underlying the cardioprotective properties of PO's bioactive constituents, highlighting the regulation of the SIRT3/SOD2 signaling pathway as a new mechanism for PO's anti-cardiovascular disease effects, and suggesting the Mixture's potential as a promising drug candidate.
L. (PO) 在治疗冠心病方面已显示出显著疗效。先前的研究确定了PO中八种对心肌细胞具有保护作用的关键活性成分,但其潜在机制仍不清楚;方法:采用网络药理学和分子对接技术来确定PO活性成分的潜在靶蛋白。通过实验模型评估其心脏保护作用及机制;结果:网络分析和分子对接显示,这些活性成分与SOD2的结合亲和力最高,表明SOD2是PO心脏保护作用的关键因素。在体内,PO提取物改善了心肌结构和功能,并提高了SOD2蛋白水平。在体外,PO的活性成分(混合物)减轻了氧化应激和细胞凋亡,上调了SIRT3并降低了乙酰化SOD2水平,导致SOD2增加和ROS水平降低。SIRT3抑制剂可逆转观察到的效果,表明SIRT3/SOD2信号通路参与其中;结论:这种综合方法阐明了PO生物活性成分心脏保护特性的关键机制,突出了SIRT3/SOD2信号通路的调节作为PO抗心血管疾病作用的新机制,并表明该混合物作为一种有前景的候选药物的潜力。