Ellagic Acid Attenuates High-Fat, High-Sucrose Diet-Induced Cardiac Fibrosis by Suppressing AGE–RAGE Signaling, Oxidative Stress, and Inflammation

A high-fat, high-sucrose (HFHS) diet promotes insulin resistance and accelerates cardiac fibrosis (CF) through advanced glycation end products (AGEs), oxidative stress, and inflammation. Ellagic acid (EA) possesses antioxidant, anti-inflammatory, and anti-glycation properties; however, its protective effects against CF and underlying molecular mechanisms remain unclear. Therefore, we investigated EA’s effects on HFHS-induced CF. Two-month-old male Wistar rats were randomly assigned to four groups (n = 6/group): control, control + 2% EA, HFHS, and HFHS + 2% EA, and maintained on respective diets for six months. Metabolic parameters, oxidative stress, AGE-related markers, histopathology, immunoblotting, and immunohistological analyses were performed. HFHS feeding induced metabolic dysfunction characterized by weight gain, increased fasting blood glucose levels, insulin resistance, dyslipidemia, myocardial disorganization, AGE accumulation, receptor for AGE (RAGE) activation, collagen deposition, and fibrotic marker expression- alpha smooth muscle actin (α-SMA). EA supplementation significantly improved metabolic abnormalities, reduced myocardial collagen fraction, AGE accumulation, RAGE activation, and α-SMA expression, thereby protecting against HFHS-induced CF.