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

• Published in: Cardiovascular drugs and therapy 2018-04, Vol.32 (2), p.147-163
• Main Authors: Kosuru, Ramoji, Kandula, Vidya, Rai, Uddipak, Prakash, Swati, Xia, Zhengyuan, Singh, Sanjay
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; Animal tissues; Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antioxidants - pharmacology; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood pressure; Blueberries; Cardiology; Complications; Coronary artery disease; Diabetes; Diabetes mellitus; Diabetes Mellitus - blood; Diabetes Mellitus - drug therapy; Diabetes Mellitus - enzymology; Diabetic Cardiomyopathies - enzymology; Diabetic Cardiomyopathies - pathology; Diabetic Cardiomyopathies - physiopathology; Diabetic Cardiomyopathies - prevention & control; Disease Models, Animal; Fructose; Gene expression; Heart diseases; Heart rate; Heme Oxygenase (Decyclizing) - metabolism; Hemodynamics - drug effects; Hypertension; Hypertrophy; Inflammasomes; Inflammasomes - metabolism; Inflammation; Inflammation - enzymology; Inflammation - prevention & control; Inflammation Mediators - metabolism; Male; Medicine; Medicine & Public Health; Mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - enzymology; Mitochondria, Heart - pathology; Morbidity; mRNA; Myocardium - enzymology; Myocardium - pathology; NF-E2-Related Factor 2 - metabolism; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Original Article; Oxidative stress; Oxidative Stress - drug effects; Pathogenesis; Pharmacology; Proteins; Rats; Rats, Sprague-Dawley; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Stilbenes - pharmacology
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-018-6780-3

Purpose 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. Methods 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. Results 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. Conclusions Collectively, PT reduced cardiac oxidative stress and inflammation in diabetic rats through stimulation of AMPK/Nrf2/HO-1 signalling.