Paper
Protective Role of 10-Dehydrogingerdione as Modulator for CETP Activity and HDL Metabolism in Cholesterol Fed Rabbits
- Authors:
- Mohamed M. Elseweidy; Fatma R. Abdallah; Samih I. Eldahmy; Mohamed A. Shaheen; Gehad M. Elnagar; Sahar E. Elswefy
- Abstract
- Background: Hyperlipidemia represents an important risk factor leading to atherosclerosis additionally life-threatening cardiovascular events such as myocardial infarction and ischemic stroke. Recent evidences referred to phytochemicals and nutraceuticals possessing cholesteryl ester transfer protein (CETP) inhibitory activity as protective agents against lipid-mediated atherosclerosis. Therefore, we studied the effect of 10-dehydrogingerdione, a novel CETP inhibitor isolated from ginger rhizomes on atherosclerosis and its underlying mechanisms based on plasma lipids, lipoprotein metabolism and oxidative stress comparable to the protective effects of atorvastatin (as standard drug) in hypercholesterolemic rabbits. Methods: Twenty four New Zealand male rabbits were randomly divided into four groups (n=6 per group). Three groups were fed an atherogenic diet for 6 weeks. Two groups received either atorvastatin (20 mg / kg body weight orally) or 10-dehydrogingerdione (10 mg / kg body weight orally after isolation and purification) daily for six weeks of treatment. One group received no treatment and served as hypercholesterolemic control group (HCG, positive control) and another one was fed normal diet and used as negative control. Blood and tissues (liver, aorta) samples were collected after six weeks for biochemical and histological analysis. Results: Rabbits fed high cholesterol diet produced a significant dyslipidemia, oxidative stress, and finally atherogenesis progression. These finding evidenced by remarkable increase in serum lipids (TC), non HDL lipoprotein (LDL-C, apo B expression) and decrement of HDL lipoprotein (HDL-C, apo-A1, apo-AII). In addition, increase in CETP level and expression in plasma and liver, MDA, ox-LDL, dense and number of foam cells of aorta was marked. Treatment of hypercholesterolemic rabbits with either of 10 -dehydrogingerdione or atorvastatin for 6 weeks successfully decrease non HDL lipoproteins, aortic foam cell number, increase protective HDL lipoprotein, its apolipoproteins and produced inhibitory effect on CETP. However, 10-dehydrogingerdione exerted better effect than atorvastatin on serum HDL-C (p<0.001), CETP mass (p<0.001), CETP expression (p<0.05), apo A-1 and apo A-II (p<0.01), more reduction in the density, number of foam cells and improvement of the intimal lesions of aorta. Conclusions: 10-dehydrogingerdione may provide a protective effect against atherosclerosis compared to atorvastatin. This effect may be through reduction of foam cell number, its potential CETP inhibition, increase HDL-C and wards off oxidation in hypercholesterolemic rabbits.
- Keywords
- Hypercholesterolemia; CETP Inhibition; Apolipoprotein Metabolism; Oxidative stress; Atorvastatin; 10-Dehydrogingerdione
- StartPage
- 28
- EndPage
- 36
- Doi
- 10.5963/BER0302001