Novel prevention insights into depletion of oxidative stress status through regular exercise and grape seed effective substance in heart ischemia rat model

Myocardial ischemia (MI) is recognized as the most frequent cardiovascular disease which is the dominant cause of global morbidity and mortality. Artificial intelligence tools and integrative data analysis revealed superoxide dismutase, catalase, glutathione peroxidase, gap junction protein α, myosin heavy chains, and zinc finger transcription factor GATA4 are engaged in oxidative stress and in cardiomyopathy. Network analysis indicated that MAPK3 might be the highest distribution property and cut point in this network, which could be a potential candidate for preventing and treating oxidative stress in heart tissue. Among antioxidant agents, grape seed extract (GSE) is an effective substance that altered antioxidant status in heart tissue. Considering drug discovery methods, we illustrated that GSE might target the MAPK3 protein with sufficient binding affinity. Moreover, we found that low‐ and moderate‐intensity training might prevent the depletion of antioxidants after MI. GSE consumption altered the levels of superoxide dismutase, glutathione peroxidase, and catalase after 14 weeks. Therefore, the interaction of low‐ and moderate‐intensity training and GSE had a synergistic effect on the antioxidant status and relative expression of the Mapk3. Moreover, the interaction of high‐intensity training and GSE had a compensatory mechanism that could scavenge reactive oxygen species and improve endogenous antioxidants and modulate the Mapk3 level in MI rats. Consequently, we displayed positive influence and synergic effects of simultaneous GSE prescription and regular physical activity for 14 weeks to prevent acute and chronic heart ischemia cardioprotective phenomenon. Furthermore, the capacitation oxidative stress and relative expression of the Mapk3 was significantly increased by GSE and regular exercise.