Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Myocardial ischemia-reperfusion (I/R) injury represents a critical complication in cardiovascular diseases, profoundly influencing patient prognosis. Objectives: This study endeavors to elucidate the protective mechanisms and effects of Platycodin-D (PD) on myocardial ischemia-reperfusion injury (MIRI). Methods: A rat model of myocardial ischemia-reperfusion was employed to assess the impact of PD treatment on cardiac performance, myocardial injury biomarkers (CK-MB, LDH, cTnI), and infarct size. Further mechanistic insights were gained through Western blot and JC-1 staining, which analyzed the modulation of the HIF-1?/BNIP3 signaling pathway and mitochondrial autophagy by PD. Results: PD treatment markedly improved cardiac function, decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI), and reduced infarct size. Mechanistically, PD was found to regulate the HIF-1?/BNIP3 signaling pathway, inhibit mitochondrial autophagy, and enhance mitochondrial function. Western blot and JC-1 staining confirmed that PD increases mitochondrial membrane potential and reduces the number of damaged mitochondria in cardiomyocytes. Conclusions: This study underscores the significant protective effects of Platycodin-D against myocardial ischemia-reperfusion injury, presenting a promising therapeutic approach for cardiovascular disease management.