secoisolariciresinol-diglucoside and Atherosclerosis

Many natural products, including vitamin E, garlic, purpurogallin, flaxseed and its components [secoisolariciresinol diglucoside (SDG) and flax lignan complex (FLC)] and resveratrol have been reported to suppress hypercholesterolemic atherosclerosis. It is known that all of the drugs that suppress the development of atherosclerosis do not regress and/or slow the progression of atherosclerosis. To be of potential benefit in patients with established atherosclerosis, a drug should produce regression and/or slow the progression of atherosclerosis. In this review, the effects of vitamin E, SDG and FLC in the regression and slowing of progression of hypercholesterolemic atherosclerosis and their mechanisms have been described. The effectiveness of vitamin E in patients with established coronary disease is very controversial. However, in experimental animal controlled studies, vitamin E does not regress or slow the progression of hypercholesterolemic atherosclerosis. The mechanisms of the ineffectiveness of vitamin E in regression and slowing of progression of atherosclerosis have been discussed. SDG is effective in slowing the progression of atherosclerosis and partially effective in regression of hypercholesterolemic atherosclerosis. These effects are associated with reduction in oxidative stress. FLC does not regress hypercholesterolemic atherosclerosis but slows the progression of hypercholesterolemic atherosclerosis. Slowing of progression is associated with reduction on oxidative stress. In conclusion, vitamin E does not regress or slow the progression of established atherosclerosis. SDG slows the progression and regresses established atherosclerosis. FLC does not regress but slows the progression of established atherosclerosis.

Topics: Animals; Antioxidants; Atherosclerosis; Biological Products; Butylene Glycols; Disease Progression; Flax; Glucosides; Humans; Hypercholesterolemia; Lignans; Oxidative Stress; Phytotherapy; Vitamin E

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis in rabbits. It is however not known if SDG would produce regression of atherosclerosis. The objectives of this study were to determine (i) if SDG produces regression of atherosclerosis; (ii) if regression is associated with reduction in serum lipids, oxidative stress or both; and (iii) if the duration of treatment has an effect on regression. Rabbits were assigned to five groups: Group I, regular diet (control); Group II, 0.5% cholesterol diet for 2 months (mo); Group III, same as Group II but followed by regular diet for 2 mo; Group IV, same as Group II and followed by regular diet with SDG (20mg x kg body wt(-1) x day(-1) PO) for 2 mo; and Group V, same as Group IV but SDG treatment for an additional 2 mo. Blood samples were collected from rabbits before and at monthly intervals thereafter on their respective diet regimen for measurement of triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for assessment of atherosclerotic lesions, aortic MDA and aortic chemiluminescence (Aortic-CL), a measure of antioxidant reserve. MDA and Aortic-CL provide an index of oxidative stress. Increases in serum TG, TC, LDL-C, HDL-C and the risk ratio TC/HDL-C in Group II were associated with an increase in oxidative stress and development of atherosclerosis (57% of aortic intimal surface covered with lesions). Serum lipids decreased to a similar extent in Groups III-V, however atherosclerotic lesions were 84%, 63% and 44%, respectively in Groups III-V. There were more atherosclerotic lesions in Group III (+48.9%) as compared to Group II. The atherosclerotic lesions decreased by 24% and 45%, respectively in Groups IV and V compared to Group III. The reduction in atherosclerotic lesions was associated with a reduction in oxidative stress. These results suggest that (i) regular diet following a high cholesterol diet accelerates atherosclerosis in spite of a decrease in serum lipids; (ii) SDG treatment prevents the progression of atherosclerosis on a regular diet following a high cholesterol diet; (iii) prevention of progression is associated with a reduction of aortic oxidative stress and not with reductions in serum lipids; (iv) a longer duration of treatment reduces the progression of athero

Topics: Animals; Aorta; Atherosclerosis; Butylene Glycols; Flax; Glucosides; Hypercholesterolemia; Lipids; Luminescence; Malondialdehyde; Oxidative Stress; Plant Preparations; Rabbits

Reactive oxygen species (ROS) have been implicated in the development of hypercholesterolemic atherosclerosis. Hypercholesterolemia increases the levels of platelet activating factor (PAF) and cytokines which are known to stimulate granulocytes and endothelial cells to produce ROS. Pentoxifylline (PTX) is an inhibitor of cytokines and PAF and would reduce the generation of ROS by granulocytes and endothelial cells. PTX therefore would be expected to reduce the development of hypercholesterolemic atherosclerosis. New Zealand white female rabbits were assigned to four groups: Group I (n=12), control; Group II (n=5), PTX control (40 mg/kg body weight daily orally); Group III (n=13), 0.5% cholesterol; Group IV (n=9), 0.5% cholesterol+PTX (40 mg/kg body weight daily orally). Blood samples were collected before (0 time) and after 1 and 2 months on experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product. At the end of 2 months the aorta was removed for measurement of atherosclerotic plaques, MDA, and aortic tissue chemiluminescence (Ao-CL), a marker for antioxidant reserve. Rabbits in Group III developed atherosclerosis (56.61+/-6.90% of the intimal surface of aorta was covered with atherosclerotic plaques) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, TC/HDL-C, MDA and aortic MDA and antioxidant reserve. PTX reduced the development of atherosclerosis by 38.1% and this was associated with decreases in serum MDA by 32%, aortic MDA by 37%, and antioxidant reserve by 17.3% without changes in the serum lipids. These results suggest that ROS generated during hypercholesterolemia via cytokines and PAF may in part contribute to the development of hypercholesterolemic atherosclerosis and that suppression of production and activity of cytokines and PAF may reduce the development of hypercholesterolemic atherosclerosis.

Topics: Animals; Antioxidants; Aorta; Atherosclerosis; Body Weight; Butylene Glycols; Cholesterol, Dietary; Female; Glucosides; Hypercholesterolemia; Lipids; Luminescence; Malondialdehyde; Pentoxifylline; Rabbits