INVESTIGATION OF BIOACTIVE FLAVONOID SOURCED FROM CITRUS FRUITS ON ITS EFFECT UPON CARDIAC HYPERTROPHY: AN EXPERIMENTAL STUDY

Abstract

Objective: Cardiac hypertrophy is an adaptive process of the heart. It is a leading cause for heart failure, which in turn has a high mortality rate. Hesperidin (HES) is a bioactive flavanone glycoside with agonistic activity on Peroxisome Proliferator-Activated Receptor gamma (PPAR-gamma), reported to be an inhibitor of cardiac hypertrophy signalling pathways. Therefore, we investigated the cardio-protective effect of this bioactive flavonoid in isoproterenol induced cardiac hypertrophy. Design and method: Male albino Wistar rats were divided into 6 groups (n = 6) and administered isoproterenol (3 mg/kg/day s.c.) or hesperidin (200 mg/kg/day, p.o.) and isoproterenol or enalapril (30 mg/kg/day p.o.) and isoproterenol or a combination of hesperidin and enalapril for 28 days. On the 29th day, rats were anaesthetized followed by cannulation of coronary artery to record hemodynamic parameters. Blood sample was collected and heart was excised to evaluate for parameters like biochemical, histopathological, ultrastructural and immunohistochemical studies. Results: Hesperidin significantly normalized heart weight/body weight ratio and cardiomyocyte area in the treated rats. Moreover, hesperidin improved cardiac function and attenuated pathological changes as seen in the heart tissue sections. A decline in the levels of cardiac injury markers (CK-MB, LDH) and inflammatory markers TNF-alpha, IL-6) was observed. Additionally, hesperidin suppressed oxidative stress and apoptosis along with an increased PPAR-gamma expression. Conclusions: Hesperidin has a good potential for attenuation of cardiac hypertrophy and acts by virtue of its PPAR-gamma agonistic, anti-inflammatory, anti-apoptotic and anti-oxidant properties.