Pterostilbene Decreases Cardiac Oxidative Stress and Inflammation via Activation of AMPK/Nrf2/HO-1 Pathway in Fructose-Fed Diabetic Rats

Ramoji Kosuru, Vidya Kandula, Uddipak Rai, Swati Prakash, Zhengyuan Xia, Sanjay Singh

Oxidative stress has a pivotal role in the pathogenesis of diabetes-associated cardiovascular problems, which has remained a primary cause of the increased morbidity and mortality in diabetic patients. It is of paramount importance to prevent the diabetes-associated cardiac complications by reducing oxidative stress with the help of nutritional or pharmacological agents. Pterostilbene (PT), the primary antioxidant in blueberries, has recently gained attention for its promising health benefits in metabolic and cardiac diseases. However, the mechanism whereby PT reduces diabetic cardiac complications is currently unknown. Sprague-Dawley rats were fed with 65% fructose diet with or without PT (20 mg kg-1 day-1) for 8 weeks. Heart rate and blood pressure were measured by tail-cuff apparatus. Real-time PCR and western blot experiments were executed to quantify the expression levels of mRNA and protein, respectively. Fructose-fed rats demonstrated cardiac hypertrophy, hypertension, enhanced myocardial oxidative stress, inflammation and increased NF-κB expression. Administration of PT significantly decreased cardiac hypertrophy, hypertension, oxidative stress, inflammation, NF-κB expression and NLRP3 inflammasome. We demonstrated that PT improved mitochondrial biogenesis as evidenced by increased protein expression of PGC-1α, complex III and complex V in fructose-fed diabetic rats. Further, PT increased protein expressions of AMPK, Nrf2, HO-1 in cardiac tissues, which may account for the prevention of cardiac oxidative stress and inflammation in fructose-fed rats. Collectively, PT reduced cardiac oxidative stress and inflammation in diabetic rats through stimulation of AMPK/Nrf2/HO-1 signalling.