Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation

Abstract

Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders.

EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice

“…Visceral fat obesity is often associated with increased risk for diseases such as atherosclerosis, dyslipidemia, hypertension, cerebrovascular thrombosis, diabetes and ischemic heart disease234. Particularly in the heart, obesity has a strong impact on left ventricle hypertrophy, myocardial fibrosis and atrial fibrillation that eventually leads to heart failure5.…”

Punicalagin Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via Activation of AMPK

“…Previous studies have shown that PUN exerts considerable antioxidant properties in lipopolysaccharide-induced macrophages and exhibits neuroprotective effects against cerebral ischemia-reperfusion insult via its anti-oxidant potential (Yaidikar et al, 2014). Moreover, it is reported that PUN prevents high-fat diet-induced cardiac metabolic disorders (Cao et al, 2015). These studies suggested PUN may provide cardioprotection against MI/R injury via anti-oxidant action.…”

“…Punicalagin (PUN) is widely recognized as the major active compound in pomegranate juice, which exerted beneficial anti-oxidative effects similar to pomegranate juice (Chen et al, 2012;Zou et al, 2014). Attractively, recent studies showed that PUN treatment attenuated cerebral ischemia reperfusion-induced oxidative brain injury (Yaidikar et al, 2014) and prevented cardiac metabolic disorders in high-fat diet-fed rats (Cao et al, 2015). These studies suggest that PUN may exert protective effects on MI/R injury.…”

“…Interestingly, a recent study revealed that PUN activated AMPK by decreasing the cellular ATP/ADP ratio in cardiomyocytes (Cao et al, 2015), which indicates that PUN might reduce MI/R injury via activation of AMPK. In this study, we observed that the phosphorylation of AMPK is significantly increased after I/R, accompanied by increased phosphorylation of its downstream target ACC.…”

“…It has been demonstrated that AMPK can upregulate cellular antioxidant enzyme systems such as manganese superoxide dismutase (Mn-SOD), and catalase, thereby reducing oxidant-induced damage (Wu et al, 2014). Importantly, PUN has been demonstrated to ameliorate high-fat diet-induced mitochondrial impairment through the AMPK signaling pathway (Cao et al, 2015). However, the role of AMPK signaling pathway in PUN's anti-oxidative effects against MI/R injury is still unknown.…”