Protective effects of ginsenoside F 2 on isoproterenol-induced myocardial infarction by activating the Nrf2/HO-1 and PI3K/Akt signaling pathways

Ginsenoside F 2 (GF 2 ) serves as the principal intestinal metabolite resulting from the oral intake of Panax ginseng and Panax quinquefolius, exhibiting antioxidative, hypolipidemic, antitumor, and anti-inflammatory properties. Nevertheless, its effect on myocardial infarction (MI) is still unknown. The purpose of this study is to investigate the protective effect and the underlying mechanisms of GF 2 against isoproterenol (ISO)-induced MI. ISO-induced H9c2 cardiomyocytes and MI rat models were utilized as in vitro and in vivo models to evaluate the impact of anti-MI of GF 2. The underlying mechanisms were investigated using a variety of methodologies, including electrocardiography, Western blot analysis, histopathological examination, immunofluorescence, immunohistochemistry, and ELISA techniques. In vivo experiments, our results indicated that GF 2 significantly ameliorated ISO-induced electrocardiographic (ECG) abnormalities, myocardial fiber necrosis, rupture, fibrosis of myocardial tissues, and suppressed cardiac enzyme activities. Meanwhile, GF 2 notably raised the activity of antioxidant enzymes like CAT, GSH, and SOD. Furthermore, it downregulated Keap1 expression level while upregulating NQO1, Nrf2, and HO-1 expression levels. Additionally, GF 2 suppressed the expression of the cleaved caspase-3 and pro-apoptotic protein Bax while promoting the expression of anti-apoptotic proteins Bcl-2, p-PI3K, and p-Akt. TUNEL fluorescence results also demonstrated that GF 2 effectively inhibited cardiomyocyte apoptosis. Furthermore, consistent with the results of animal experiments, GF 2 considerably attenuated ROS generation, changed apoptosis and mitochondrial function, and reduced oxidative stress in ISO-induced H9c2 cardiomyocytes through activating Nrf2/HO-1 and PI3K/Akt signaling pathways. Taken together, GF 2 ameliorated MI by preventing cardiocyte apoptosis, oxidative stress, and mitochondrial dysfunction via modulating the Nrf2/HO-1 and PI3K/Akt signaling pathways, showing potential as a treatment strategy for treating MI.