(Circulation. 1999;99:1355-1362.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Reduction of Serum Cholesterol and Hypercholesterolemic Atherosclerosis in Rabbits by Secoisolariciresinol Diglucoside Isolated From Flaxseed
From the Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
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 
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.
Key Words: atherosclerosis • hypercholesterolemia • flaxseed • chemiluminescence • antioxidants
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