β-Sitosterol Protects against Myocardial Ischemia/Reperfusion Injury via Targeting PPARγ/NF-κB Signalling

Myocardial ischemia/reperfusion (I/R) injury is a clinically severe complication, which can cause high rates of disability and mortality particularly in patients with myocardial infarction, yet the molecular mechanisms underlying this process remain unclear. This study aimed to explore the protective effects of beta-sitosterol against myocardial I/R injury and to elucidate the underlying molecular mechanisms. Our results showed that hypoxia/reoxygenation (H/R) treatment suppressed cell viability, induced cell apoptosis and reactive oxygen species production, increased caspase-3 and -9 activities, upregulated caspase-3 and -9 protein expressions, downregulated the Bcl-2 protein expression, and reduced the mitochondrial membrane potential. beta-Sitosterol treatment attenuated H/R-induced cardiomyocyte injury. Moreover, beta-sitosterol treatment counteracted the inhibitory effects of H/R treatment on the peroxisome proliferator-activated receptor gamma (PPAR gamma) expression and enhanced effects of H/R treatment on the NF-kappa B expression in cardiomyocytes. Furthermore, inhibition of PPAR gamma impaired the protective actions of beta-sitosterol against H/R-induced cardiomyocyte injury. In the I/R rats, beta-sitosterol treatment reduced the myocardial infarcted size and apoptosis, which was attenuated by the inhibition of PPAR gamma. In conclusion, our results demonstrate that beta-sitosterol protected against in vitro H/R-induced cardiomyocyte injury and in vivo myocardial I/R injury. The beta-sitosterol-mediated cardioprotective effects may involve the modulation of PPAR gamma/NF-kappa B signalling during myocardial I/R injury. Further studies are required to further explore the clinical application of beta-sitosterol in the myocardial I/R injury.