Department of Pharmacy, Chifeng Municipal Hospital, Chifeng, China.
School of Pharmacy, Inner Mongolia Medical University, Huhehot, China.
Sci Rep. 2021 Jan 12;11(1):664. doi: 10.1038/s41598-020-80861-6.
Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by HO in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against HO-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX's cardioprotection effect.
三味檀香散（SWTX）是一种传统的蒙藏药，含有多种活性分子，可缓解心绞痛并改善冠心病（CHD）患者的康复。在我们之前的研究中，从系统的角度分析了 SWTX 对 CHD 的药理作用。生物信息学预测表明，PI3K/Akt/FoxO3a 通路是 SWTX 治疗冠心病的重要通路之一。在此基础上，本研究旨在评估 SWTX 在体内急性心肌缺血再灌注（MIR）大鼠和体外 H9c2 心肌细胞氧化应激诱导下 HO 中的作用，并进一步探讨 PI3K/Akt/FoxO3a 通路在这些过程中的参与情况。在体外生理条件下，SWTX 对心率和收缩幅度没有任何修饰作用。然而，在 MIR 损伤下，SWTX 预处理提供了显著的保护作用，包括减少体内 ST 段抬高、病理学变化和心肌梗死面积，同时，SWTX 的一些单体表现出抗氧化能力并抑制体外心肌细胞凋亡。这种作用与 PI3K/Akt/FoxO3a 信号通路下游的激活以及通过 qRT-PCR、Western blot 和免疫荧光检测实验验证的 FoxO3a 下游促凋亡 Bim 的调节有关。在体外，用 PI3K 抑制剂 LY294002 阻断 Akt 和 p-FoxO3a 的激活，可有效抑制 SWTX 几种活性单体（包括槲皮素、马钱子素、甲基丁香酚和 Santol）对 HO 诱导损伤的保护作用。综上所述，这些结果表明，SWTX 可减少 I/R 损伤，PI3K/Akt/FoxO3a 通路参与了这一过程的保护作用，至少部分归因于 GZ 的 gallogen（G3）和 quercetin（G8）、RDK 的 methyleugenol（R2）和 macelignan（R7）以及 TX 的 santol（T1）。
