Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high fat diet induced hypercholesterolemic rats

Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats H ypercholesterolemia, the presence of high levels of cholesterol in the blood, is a serious health concern around the world.It is the key risk factor for cardiovascular disease (CVD).Coronary heart disease and stroke are the number one cause of death worldwide, accounting for 17.9 million deaths every year, the equivalent of 31% of all global deaths [1].To improve the global CVD burden, the World Health Organization has encouraged tobacco control, dietary salt reduction, and strengthening of CVD management in primary health care systems [2].The major causes of hypercholesterolemia are a sedentary lifestyle, an increased intake of saturated fatty acids, tobacco use, an unhealthy diet, and excessive alcohol consumption.Secondary causes include hypothyroidism, nephrotic syndrome, cholestasis, and certain Objectives: Hypercholesterolemia is a serious health concern throughout the world.It is the key risk factor for cardiovascular disease (CVD).The aim of this study was to investigate the antihypercholesterolemic potential of fraxetin on hypercholesterolemic rats given a high-fat diet (HFD).Methods: A total of 24 male albino Wistar rats weighing 180-200 g were used in this study and were divided into 4 groups: Control (Group 1), hypercholesterolemia-induced (Group 2), hypercholesterolemia-induced and treated with fraxetin (75 mg/kg) (Group 3), and hypercholesterolemia-induced and treated with simvastatin (10 mg/kg) (Group 4).The plasma lipid profile, status of enzymatic and non-enzymatic antioxidants, and the levels of oxidative stress markers of all groups were analyzed.Results: The plasma level of total cholesterol, triglycerides, very low-density lipoprotein, and low-density lipoprotein cholesterol were significantly increased, and the level of high-density lipoprotein cholesterol was significantly decreased in the hypercholesterolemic rats in comparison with the normal, control rats.Oral administration of fraxetin significantly (p<0.05)reversed these altered parameters to near-normal levels.In addition, fraxetin treatment significantly (p<0.05)increased the status of antioxidants with a concomitant reduction in oxidative stress markers.Oil red O staining of the thoracic aorta revealed widespread deposition of lipid droplets in the hypercholesterolemic rats (Group 2), whereas the hypercholesterolemic rats treated with fraxetin or simvastatin showed only scattered droplets of fat.The effect of fraxetin on various biochemical parameters was comparable to that of simvastatin. Conclusion:The results of this study indicated that the lipid-lowering potential of fraxetin at the dosage of 75 mg/ kg was comparable to that of the antihypercholesterolemic drug simvastatin.Further studies on the molecular mechanism of action of fraxetin are warranted and in progress in our laboratory at the time of writing.