Flax Lignan Complex Slows Down the Progression of Atherosclerosis in Hyperlipidemic Rabbits

Flax lignan complex suppresses the development of hypercholesterolemic atherosclerosis. However, it is not known whether flax lignan complex would slow down the progression of hypercholesterolemic atherosclerosis. This study was carried out to determine whether flax lignan complex slows down the progression of already developed atherosclerosis, and whether this effect is associated with reductions in serum lipids and oxidative stress. The studies were conducted in 4 groups of rabbits: group I, regular diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (4 months); group IV, 0.25% cholesterol diet (2 months) followed by 0.25% cholesterol diet plus flax lignan complex (2 months). Serum lipids and oxidative stress parameters (malondialdehyde, antioxidant reserve, white blood cell chemiluminescence) were measured before and at monthly intervals thereafter on their respective diets. Aortas were removed at the end of the protocol for assessment of atherosclerosis and oxidative stress. Atherosclerosis in group II was associated with hyperlipidemia and increased oxidative stress. Significant areas of the aortic intimal surfaces from group II (37.76% + 7.96%), group III (76.6% + 9.04%), and group IV (52.95% + 10.29%) were covered with atherosclerotic plaques. Group IV rabbits had 40% more atherosclerotic lesions than group II but 31% fewer lesions than group III. The flax lignan complex�induced reduction in the progression of atherosclerosis was associated with reductions in oxidative stress. In conclusion, flax lignan complex was effective in slowing down the progression of atherosclerosis by 31%, and this effect was associated with a reduction in oxidative stress. (Authors abstract)
Reactive oxygen species (ROS) have been implicated in causing hypercholesterolemic atherosclerosis which antioxidants are effective in the suppressing. Flax lignin complex contains secoisolariciresinol diglucoside (SDG; 34% to 38%), cinnamic acid glucoside (15% to 21%), and hydroxymethylglutaric acid (9.6% to 11.0%). SDG and cinnamic acid are antioxidants. Although flax lignan complex suppresses the development of atherosclerosis, it is not known whether it would slow down the progression of atherosclerosis. The main objectives of this investigation were to determine whether (1) flax lignan complex slows down the progression of already developed hypercholesterolemic atherosclerosis; and (ii) slowing of the progression of atherosclerosis is associated with reductions in oxidative stress and serum lipids. The effects of flax lignan complex on the progression of pre-existing atherosclerosis in rabbits on a high-cholesterol diet were assessed.  The high cholesterol diet increased the serum levels of TC, HDL-C, LDL-C, and the ratio of TC/HDL-C in the rabbits in this study. Serum TG decreased in this study. The risk ratio TC/HDL-C was not affected by flax lignan complex. Hypercholesterolemia could increase the levels of oxygen radicals. Malondialdehyde (MDA) content of the aortic tissue was elevated in the rabbits on the high-cholesterol diet, and levels were higher with a longer duration when compared to a shorter duration of similar diets.  MDA content in the aortas of group IV was reduced by 21% compared to group II, and by 42% compared to group III. This reduction in the levels of MDA could not be related to serum lipids because serum lipid levels were similar in groups II, III, and IV. The reduction in the levels may be due to the antioxidant activity of flax lignan complex and/or due to a tendency for a normalization of the antioxidant reserve in the aorta. The normalization of antioxidant reserve in the flax lignan�treated group on the high-cholesterol diet could be due to reduced oxidative stress because of the antioxidant activity of the lignan complex, hence a reduced need for induction of antioxidant reserve. Flax lignan complex reduced the progression of hypercholesterolemic atherosclerosis in this study which could be due to a decrease in the oxidative stress as evidenced by a decrease in aortic MDA and near normalization of antioxidant reserve.  The author also speculated that flax lignin complex may alter the proatherogenic events. However, more studies are necessary to ascertain the extent to which flax lignan complex slows the progression of hypercholesterolemic atherosclerosis. (Editors comments)