Key Findings
Oxygen free radicals (OFRs) have been implicated in the development of hypercholesterolemic atherosclerosis. In this study, the effects of a high-cholesterol diet in rabbits with or without SDG treatment on the genesis of atherosclerosis, serum lipid profile [triglycerides (TG), total cholesterol (TC), HDL cholesterol (HDL-C), LDL-C, VLDL cholesterol (VLDL-C)], aortic tissue MDA, and antioxidant reserve. Gross and microscopic changes in the aorta were also investigated. The results suggest that hypercholesterolemic atherosclerosis is associated with an increase in oxidative stress in aorta and that SDG is effective in reducing hypercholesterolemic atherosclerosis by reducing oxidative stress and lowering serum levels of cholesterol and LDL-C and raising serum levels of HDL-C in the early stage. SDG therefore may be useful in preventing hype rcholesterolemic atherosclerosis and lowering the relative risk of coronary artery disease.
ABSTRACT
Background—Secoisolariciresinol diglucoside (SDG) is a plant lignan isolated from flaxseed. Lignans are platelet activating factor–receptor antagonists that would inhibit the production of oxygen radicals by polymorphonuclear leukocytes. SDG is an antioxidant. Antioxidants studied thus far are known to reduce hypercholesterolemic atherosclerosis. The objective of this study was to determine the effect of SDG on various blood lipid and aortic tissue oxidative stress parameters and on the development of atherosclerosis in rabbits fed a high-cholesterol diet.
Methods and Results— Rabbits were assigned to 4 groups: group 1, control; group 2, SDG control (15 mg. kg body wt-1. d-1 PO); group 3, 1% cholesterol diet; and group 4, same as group 3 but with added SDG (15 mg. kg body wt-1. d-1 PO). Blood samples were collected before (time 0) and after 4 and 8 weeks of experimental diets for measurement of serum triglycerides, total cholesterol (TC), and LDL, HDL, and VLDL cholesterol (LDL-C, HDL-C, and VLDL-C). The aorta was removed at the end of the protocol for assessment of atherosclerotic plaques; malondialdehyde, an aortic tissue lipid peroxidation product; and aortic tissue chemiluminescence, a marker for antioxidant reserve. Serum TC, LDL-C, and the ratios LDL-C/HDL-C and TC/HDL-C increased in groups 3 and 4 compared with time 0, the increase being smaller in group 4 than in group 3. Serum HDL-C decreased in group 3 and increased in group 4 compared with time 0, but changes were lower in group 3 than in group 4. SDG reduced TC and LDL-C by 33% and 35%, respectively, at week 8 but increased HDL-C significantly, by>140%, as early as week 4. It also decreased TC/LDL-C and LDL-C/HDL-C ratios by approximately 64%. There was an increase in aortic malondialdehyde and chemiluminescence in group 3, and they were lower in group 4 than in group 3. SDG reduced hypercholesterolemic atherosclerosis by 73%.Conclusions—These results suggest that SDG reduced hypercholesterolemic atherosclerosis and that this effect was associated with a decrease in serum cholesterol, LDL-C, and lipid peroxidation product and an increase in HDL-C and antioxidant reserve.
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