Qiliqiangxin Attenuates Oxidative Stress-Induced Mitochondrion-Dependent Apoptosis in Cardiomyocytes <i>via</i> PI3K/AKT/GSK3β Signaling Pathway

Abstract

Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, Sprague Dawley (SD) rats received left anterior descending coronary artery ligation for 4 weeks to establish a model of heart failure after acute myocardial infarction, and then were treated with QLQX for another 4 weeks. We evaluated cardiac function, oxidative stress injury, as well as the expressions of mitochondria-dependent apoptosis and its signaling factors. The results indicated that QLQX protected cardiac function and attenuated oxidative stress-induced myocardial apoptosis. Meanwhile, QLQX elevated the Bcl-2 expression, declined the expressions of Bax, cytochrome c, apoptotic protease activating factor-1 (Apaf-1), cleaved-caspase 9 and cleaved-caspase 3, and up-regulated the ratios of phospho-AKT/AKT and phospho-glycogen synthase kinase-3β (GSK3β)/GSK3β. In vitro, H9c2 cardiomyocytes were pretreated with QLQX, then exposed to H 2 O 2 for 24 h. QLQX promoted the proliferation of H9c2 cardiomyocytes induced by H 2 O 2 and reversed oxidative stress damage. Moreover, QLQX inhibited the apoptosis rate and the pro-apoptosis protein expressions, but improved the Bcl-2 expression as well as the ratios of phospho-AKT/AKT and phospho-GSK3β/ GSK3β. Meanwhile, it further ameliorated mitochondrion-related apoptosis by inhibiting the mitochondrial fission, mitochondrial permeability transition pore (MPTP) opening, and mitochondrial membrane potential (MMP) decline in H9c2 cardiomyocytes induced by H 2 O 2. In addition, all the effects of QLQX on H 2 O 2-induced mitochondria-dependent apoptosis could be blocked by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. We conclude that QLQX may ameliorate oxidative stress-induced mitochondria-dependent apoptosis in cardiomyocytes through PI3K/AKT/GSK3β signaling pathway.

Oxymatrine pretreatment protects H9c2 cardiomyocytes from hypoxia/reoxygenation injury by modulating the PI3K/Akt pathway

“…It is one of the more extensively investigated signaling pathways in clinical research. According to numerous studies, this pathway is activated following I/R injury, and effectively reduces the area of myocardial infarction, which is also the target of a number of biological molecules and drugs (14,33,34). Components of this signaling pathway were analyzed at the protein and mRNA levels to determine whether the protective effect of OMT on cardiomyocytes subjected to H/R injury was associated with this signaling pathway and to verify the pathway upstream of the Nrf2/HO-1 pathway.…”

8-Gingerol Ameliorates Myocardial Fibrosis by Attenuating Reactive Oxygen Species, Apoptosis, and Autophagy via the PI3K/Akt/mTOR Signaling Pathway

“…The 8-Gin L and 8-Gin H groups were treated with 8-Gin [10 and 20 mg/kg/d, intraperitoneally (i.p. ), respectively] ( Nieuwenhuiset al, 2010 ; Zhao et al, 2019 ), and then subcutaneously injected with ISO (10 mg/kg/d). The CAP group was treated with CAP (45 mg/kg/d, i.p.)…”

“…Due to the different chain-lengths in its molecular structure, gingerol can be subdivided into 6-, 8-and 10-gingerols (6-, 8-, and 10-Gin) (Wymann et al, 2003). Previous research has confirmed that 8-Gin (Figure 1) has various pharmacological properties, including anti-inflammatory and anti-oxidative capacities, immunosuppressive activity, and cardiotonic action (Li et al, 2018b;Takino et al, 2019;Zhao et al, 2019). However, the cardioprotective effects of 8-Gin against isoproterenol (ISO)induced MF have not yet been reported.…”

Modulatory Effects of Chinese Herbal Medicines on Energy Metabolism in Ischemic Heart Diseases

“…In rat primary cardiac microvascular endothelial cells (CMECs) subjected to hypoxia, QLQX was found to improve glucose utilization and protect CMECs against hypoxia-induced injury by promoting hypoxia-inducible factor 1-alpha (HIF-1a)-dependent glycolysis (Wang et al, 2018a). Zhao et al (2019) conducted the myocardial infarction surgery in male SD rats fed with (0.25, 0.5, and 1.0 g/kg/day) QLQX. 4 weeks after myocardial infarction, QLQX treatment protected cardiac function, ameliorated mitochondria-dependent apoptosis, and enhanced p-AKT and p-GSK3b expression.…”