Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.

Background: Ischemic heart disease is an imperative cause of high morbidity and mortality globally. The cardiac ischemia/reperfusion damage occur in both reperfusion and ischemia. Objective: In this exploration, we have planned to examine the cardio-protective action of phyllanthin against the myocardial ischemic-reperfusion injury in mice. Materials and methods: The myocardial ischemic reperfusion injury (MI-RI) stimulated via coronary artery occlusion, followed by the 10 mg/kg of phyllanthin treatment. The serum cardiac markers and pro-inflammatory markers level was investigated by using the assay kits. The expressions of oxidative stress and inflammatory markers level were investigated by immunohistochemical analysis. Lipid peroxidation, antioxidant enzymes, and ATPase levels level was examined by standard methods. The expression of oxidative stress markers were inspected by the reverse transcription polymerase chain reaction technique. The heart histology was investigated microscopically. Results: The phyllanthin treatment increased the body weight, and heart weight also diminished the infarct size in the MI/RI mice. Cardiac markers status was diminished and the blood pressure markers were augmented by the phyllanthin. Histological analysis revealed the protective role of phyllanthin. Suppressed lipid peroxidation and enhanced antioxidant enzymes were noted in the phyllanthin treated mice MI-RI mice. Phyllanthin appreciably suppressed the pro-inflammatory regulators that is, NF-αB p65, IL-6, IL-1β, and TNF-α and enhanced the antioxidant marker expressions. ATPase levels were improved by the phyllanthin in the MI-RI mice. Conclusion: These novel findings were confirmed the therapeutic role of phyllanthin against the MI-RI in mice. Hence, it can be a promising agent to treat the MI-RI induced cardiac dysfunction.

As an extensively studied quality control system, autophagy is responsible for clearance of dysfunctional organelles and damaged marcomolecules in cells. In addition to its biological recycling function, autophagy plays a significant role in the pathogenesis of metabolic syndromes such as obesity and diabetes. In particular, metabolic disorders contribute to cardiovascular disease development. As energy required to maintain cardiac cells functional is immense, disturbances in the balance between anabolic and catabolic metabolism possibly contribute to cardiovascular disorders. Therefore, an urgent need to expand our knowledge on the role of autophagy on the metabolic regulation of hearts emerges. In this review, the potential relationship between autophagic activity and cardiac metabolism is explored and we also discuss how dysregulated autophagy leads to severe cardiac disorders from the perspective of metabolic control.