Protective effects of zingerone on high cholesterol diet-induced atherosclerosis through lipid regulatory signaling pathway

Aim: A high cholesterol diet (HCD) is known to cause metabolic dysregulation, oxidative stress, cardiovascular diseases and atherogenesis. Zingerone is a pharmacologically active component of dry ginger. Zingerone has been shown to have a wide range of pharmacological properties, including scavenging free radicals, high antioxidant activity, suppressing lipid peroxidation and anti-inflammatory. This study aimed to investigate the effects of Zingerone on HCD-induced atherosclerosis in rats. Methods: Animals were divided into four categories (n = 6). Group I: normal control, Group II: zingerone control (20 mg/kg b.wt.), group III: HCD-induced atherosclerosis, Group IV: HCD + zingerone, respectively, for 8 weeks. Results: The HCD-fed rats resulted in a significant increase in an atherosclerotic lesion, lipid peroxidation, lipid profile, high-density lipoprotein concentration, cardiac markers, body weight, reduced antioxidant status, and displayed atherosclerosis. These findings were conventional by up-regulated expression of lipid regulatory genes like sterol-regulatory-element-binding protein-c (SREBP-c), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), acetyl-CoA synthetase (ACS), liver X receptor-alpha (LXR-alpha), and down-regulated expression of acetyl-CoA oxidase (ACO), peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and carnitine palmitoyl transferase-1 (CPT-1) in HCD-fed rats. These significant changes were observed in the zingerone-treated rats for the last 4 weeks. Conclusion: These findings suggest that zingerone reduced atherosclerosis by modulated the atherosclerotic lesion, lipid profile, antioxidant status and lipid regulatory gene expression in HCD-fed rats.