Apigenin suppresses the apoptosis of H9C2 rat cardiomyocytes subjected to myocardial ischemia‑reperfusion injury via upregulation of the PI3K/Akt pathway

Abstract

Apigenin, a flavonoid with multiple physiological and pharmacological activities, is associated with the prevention of cardiovascular diseases. The present study aimed to examine the roles and mechanisms of apigenin in the apoptosis of H9C2 rat cardiomyocytes, which were subjected to myocardial ischemia-reperfusion (MI/R) injury. Cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and cellular apoptosis were evaluated using cell counting kit-8 assays and flow cytometry. The content/activity of oxidative stress markers was determined using commercial kits. Western blot analysis and reverse transcription-quantitative polymerase chain reaction assays were used to measure protein and mRNA expression, respectively. The results demonstrated that apigenin had limited cytotoxicity on the viability of H9C2 rat cardiomyocytes. Apigenin reduced the oxidative stress, ROS production and cellular apoptotic capacity of MI/R-induced H9C2 cells. Apigenin additionally increased the MMP level of MI/R-induced H9C2 cells. Furthermore, apigenin modulated apoptosis-associated protein expression and phosphatidylinositol 3′-kinase (PI3K)/RAC-α serine/threonine-protein kinase (Akt) signaling in MI/R-induced H9C2 cells. Treatment with LY294002 reversed the anti-apoptotic effect of apigenin. In conclusion, apigenin suppressed the apoptosis of H9C2 cells that were subjected to MI/R injury by activating the PI3K/Akt pathway. It was suggested that apigenin may be effective as an MI/R therapy.

The Therapeutic Potential of Apigenin

“…Flavonoids, in general, are widely known for their antioxidant properties and a huge number of reports in the literature have reported the antioxidant properties of apigenin [34]. In addition, anti-hyperglycemic [35], anti-inflammatory [36], and (in myocardial ischemia) anti-apoptotic effects [37] have been reported. A recent review has summarized several of its biological effects such as cytostatic and cytotoxic activities toward various cancer cells, anti-atherogenic and protective effects in hypertension, cardiac hypertrophy, autoimmune myocarditis, among others [38].…”

Mechanotranduction Pathways in the Regulation of Mitochondrial Homeostasis in Cardiomyocytes

“…Recently, many reports have focused on the development of therapeutic compounds and drugs targeting mechanotransduction pathways to restore mitochondrial function in heart disease. For example, apigenin inhibits ROS generation, the loss of mitochondrial membrane potential, and apoptosis through PI3K/AKT signals and mitochondrial Notch1/HES1 signals, protecting H9C2 and rat heart cells from IR injury (Hu et al, 2015 ; Zhou et al, 2018 ). Additionally, melatonin promotes OPA-1–mediated mitochondrial fusion by activating YAP, thereby reducing IR-induced mitochondrial apoptosis and cardiac IR injury (Ma and Dong, 2019 ).…”

Cox-2 Negatively Affects the Protective Role of Propofol against Hypoxia/Reoxygenation Induced Cardiomyocytes Apoptosis through Suppressing Akt Signaling

“…Wu et al reported that the inhibition of apoptosis was a key factor in the Osthole-induced attenuation of myocardial I/R injury in rat models [28]. Zhou et al also indicated that Apigenin could execute its protective role in myocardial I/R injury through suppressing apoptosis of H9c2 cells [29]. Indeed, our study, in which H/R challenged H9c2 cell model was used to mimic myocardial I/R injury, showed high level of apoptosis, as well as low level of cell viability, in H9c2 cells post H/R treatment, indicating the harmful effect during reperfusion.…”