lignans and Arteriosclerosis

Hypercholesterolemia, low HDL-C and oxygen radicals have been implicated in the development of atherosclerosis. Lignan complex isolated from flaxseed contains secoisolariciresinol diglucoside (SDG), 3-hydroxy-3methylglutaric acid (HMGA) and cinnamic acids. SDG and cinnamic acids are antioxidants, and HMGA is a hypocholesterolemic agent. Antioxidants are known to reduce hypercholesterolemic atherosclerosis. The objectives of this study were to determine if lignan complex reduces (i) serum cholesterol, (ii) oxidative stress, and (iii) atherosclerosis in hypercholesterolemic rabbits. Rabbits were assigned to four groups: Group I, control; Group II, lignan complex control (lignan complex, 40 mg/kg body weight daily orally); Group III, 0.5% cholesterol; Group IV, 0.5% cholesterol diet+lignan complex, (40 mg/kg body weight daily orally). Blood samples were collected before (time 0) and after 1 and 2 months of 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 the protocol, the aorta was removed for measurement of atherosclerotic plaques, MDA and aortic tissue chemiluminescence (Aortic CL), a marker of antioxidant reserve. Rabbits in Group III developed atherosclerosis (50.84+/-6.23% of the intimal surface of the aorta was covered with atherosclerotic changes) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, MDA and aortic MDA and antioxidant reserve. Lignan complex reduced the development of atherosclerosis by 34.37% and this was associated with a decrease in serum TC by 20%, LDL-C by 14%, TC/HDL-C by 34%, serum MDA by 35% and aortic MDA by 58%. Serum HDL-C was elevated by 30% in hypercholesterolemic rabbits and by 25% in normocholesterolemic rabbits with lignan complex. Lignan complex did not affect the TC and LDL-C and serum MDA in the normocholesterolemic rabbits. However, it increased the aortic MDA in the normocholesterolemic rabbits. These results suggest that lignan complex isolated from flaxseed reduced the extent of hypercholesterolemic atherosclerosis and this effect was associated with marked decreases in oxidative stress, serum total cholesterol, LDL-C and risk ratio, and elevation of serum HDL-C. Lignan complex may, therefore, be beneficial in preventing atherosclerosis, and reducing risk factors for coronary artery disease and stroke.

Topics: Animals; Arteriosclerosis; Cholesterol, HDL; Cholesterol, LDL; Diet; Disease Models, Animal; Female; Flax; Humans; Hypercholesterolemia; Lignans; Luminescent Measurements; Malondialdehyde; Oxidative Stress; Plant Extracts; Rabbits; Risk Factors

The oxidative modification of low-density lipoprotein (LDL) plays an important role in the genesis of arteriosclerosis. The present study focused on the effects of the fruits of Morinda citrifolia on preventing arteriosclerosis. The MeOH extract and CHCl(3)-, EtOAc-, n-BuOH-, and H(2)O-soluble phases derived from the fruits of M. citrifolia were evaluated for their inhibitory activity on copper-induced LDL oxidation by the thiobarbituric acid-reactive substances (TBARS) method. The MeOH extract and EtOAc-soluble phase showed 88 and 96% inhibition, respectively. Six lignans were isolated by repeated column chromatography from the EtOAc-soluble phase. These compounds were determined by spectroscopic analysis to be 3,3'-bisdemethylpinoresinol (1), americanol A (2), americanin A (3), americanoic acid A (4), morindolin (5), and isoprincepin (6), of which 4 and 5 are novel compounds. These compounds inhibited copper-induced LDL oxidation in a dose-dependent manner. 1, 2, 5, and 6 exhibited remarkably strong activities, which were the same or better than that of the known antioxidant 2,6-di-tert-butyl-p-cresol. The IC(50) values for 1, 2, 5, and 6 were 1.057, 2.447, 2.020, and 1.362 microM, respectively. The activity of these compounds is mainly due to their number of phenolic hydroxyl groups.

Topics: Arteriosclerosis; Copper; Fruit; Lignans; Lipid Peroxidation; Lipoproteins, LDL; Magnetic Resonance Spectroscopy; Methanol; Morinda; Oxidation-Reduction; Plant Extracts; Thiobarbituric Acid Reactive Substances

Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake.. Four hundred three women with natural menopause either between 1987 and 1989 or between 1969 and 1979 were selected from the baseline data of the PROSPECT study (n=17 395). Isoflavone and lignan intake was calculated from a food-frequency questionnaire. Aortic stiffness was noninvasively assessed by pulse-wave velocity measurement of the aorta. Linear regression analysis was used. After adjustment for age, body mass index, smoking, physical activity, mean arterial pressure, follow-up time, energy intake, dietary fiber intake, glucose, and high density lipoprotein cholesterol, increasing dietary isoflavone intake was associated with decreased aortic stiffness: -0.51 m/s (95% CI -1.00 to -0.03, fourth versus first quartile, P for trend=0.07). Increasing dietary intake of lignans was also associated with decreased aortic pulse-wave velocity: -0.42 m/s (95% CI -0.93 to 0.11, fourth versus first quartile, P for trend=0.06). Results were most pronounced in older women: for isoflavones, -0.94 m/s (95% CI -1.65 to -0.22, P for trend=0.02), and for lignans, -0.80 m/s (95% CI -1.85 to -0.05), fourth versus first quartile.. The results of our study support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older women.

Topics: Aged; Aged, 80 and over; Aorta; Arteriosclerosis; Blood Flow Velocity; Compliance; Diet; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Lignans; Middle Aged; Phytoestrogens; Plant Preparations; Plants; Postmenopause; Regression Analysis; Risk Factors

Restenosis is a common complication after balloon angioplasty. A number of cytokines, chemotactic factors and growth factors may be involved. Several antioxidants have been shown to inhibit intimal thickening after balloon injury in hyperlipidemic animals.. The effects of magnolol on the expression of monocyte chemotactic protein-1 (MCP-1) and intimal response in balloon injured aorta of cholesterol-fed rabbits were investigated.. Male New Zealand white rabbits were fed a 2% high cholesterol (HC) diet together with daily intramuscular injection of either 1 microg/kg B.W. of magnolol (HC-M, n = 10) or vehicle (propylene glycol) as a control (HC-C, n = 10) for a total of 6 weeks. Another 10 rabbits fed a regular diet also served as a control (C) group. A balloon denudation of abdominal aorta was performed in each group at the end of the third week. The aortas were harvested at the end of 6 weeks.. Magnolol treatment significantly inhibited Cu2+-induced LDL oxidation in cholesterol-fed rabbits and reduced atheroma formation [atheroma area ratio: 0.10 +/- 0.03 (HC-M) versus 0.33 +/- 0.07 (HC-C), p < 0.05] in thoracic aortas without lowering serum cholesterol. The intimal response was significantly attenuated in the HC-M rabbits when compared to those of the HC-C group [intimal thickness: 88.95 +/- 14.91 microm (HC-M) versus 198.02 +/- 20.35 microm (HC-C), p < 0.05; intimal area: 278.21 +/- 43.16 x 10(3) microm2 (HC-M) versus 642.70 +/- 65.01 x 10(3) microm2 (HC-C), p < 0.05]. The MCP-1 mRNA and protein expression were reduced in the HC-M group compared to the HC-C and C groups.. The inhibitory effects on intimal hyperplasia and MCP-1 expression might be attributed to the antioxidant capacity of magnolol instead of lowering serum cholesterol. Magnolol may offer some protection against postangioplasty restenosis.

Topics: Angioplasty, Balloon; Animals; Antioxidants; Aorta; Arteriosclerosis; Biphenyl Compounds; Chemokine CCL2; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Lignans; Male; Oxidation-Reduction; Rabbits; RNA, Messenger; Triglycerides; Tunica Intima; Wounds and Injuries

Flaxseed (Type I flaxseed) with 51-55% alpha-linolenic acid in its oil and richest source of plant lignans, has been shown to reduce hypercholesterolemic atherosclerosis by 46% without lowering serum lipids. Antiatherogenic activity was claimed to be due to its alpha-linolenic acid and/or lignan content. If alpha-linolenic acid component of flaxseed is responsible for antiatherogenic activity, then, CDC-flaxseed (Type II flaxseed) which has similar oil and lignan content but has very little (2-3% of the total oil) alpha-linolenic acid would have no antiatherogenic effect. An investigation, therefore, was made of Type II flaxseed on high cholesterol diet-induced atherosclerosis and serum lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C)] in rabbits. Rabbits were assigned to four groups: Group I, Control; Group II, Type II flaxseed diet (7.5 g/kg orally daily); Group III, 1% cholesterol diet; Group IV, 1% cholesterol diet supplemented with Type II flaxseed (7.5 g/kg orally daily). Blood samples were collected before (0 time) and after 4 and 8 weeks of experimental diets for measurement of serum lipids. Aorta was removed at the end of 8 weeks for assessment of atherosclerotic plaques. Serum TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C were lower in Group IV as compared to Group III by 14 and 31%, 17 and 32%, 28 and 34% and 24 and 32%, respectively, at 4 and 8 weeks. HDL-C was not affected by Type II flaxseed in hypercholesterolemic rabbit. TG and VLDL-C were markedly increased in Group IV as compared to Group III. Type II flaxseed reduced the development of atherosclerosis by 69%. Histological changes in the atherosclerotic regions were qualitatively similar in Groups III and IV. Results indicate that reduction in hypercholesterolemic atherosclerosis by Type II flaxseed is due to a decrease in serum TC and LDL-C. In conclusion, antiatherogenic activity of Type II flaxseed is not due to alpha-linolenic acid.

Topics: alpha-Linolenic Acid; Animals; Aorta; Arteriosclerosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Flax; Hypercholesterolemia; Lignans; Lipids; Rabbits; Triglycerides

Oxygen free radicals (OFRs) have been implicated in the development of hypercholesterolemic atherosclerosis. Flax seed is the richest source of omega-3 fatty acid and lignans. omega-3 Fatty acid suppresses the production of interleukin-1 (IL-1), tumor necrosis factor (TNF) and leukotriene B4 (LTB4), and of OFRs by polymorphonuclear leukocytes (PMNLs) and monocytes. Lignans possess anti-platelet activating factor (PAF) activity and are antioxidant. PAF, IL-1, TNF and LTB4 are known to stimulate PMNLs to produce OFRs. Flaxseed would, therefore, reduce the levels of OFRs and hence would prevent the development of hypercholesterolemic atherosclerosis. The effects of dietary flax seed on a high cholesterol diet induced atherosclerosis, lipid profile and OFR-producing activity of PMNLs (PMNL-CL) were investigated in rabbits. The rabbits were divided into 4 groups: group I, control; group II, flax seed diet (7.5 g/kg daily, orally); group III, 1% cholesterol diet; and group IV, same as group III but received flax seed (7.5 g/kg daily, orally). Blood samples were collected before and after 4 and 8 weeks on their respective diets for biochemical measurements and aortae were removed at the end of 8 weeks for estimation of atherosclerotic changes. The high cholesterol diet increased the serum level of total cholesterol (TC) and PMNL-CL without altering the levels of serum triglycerides (TG). These changes were associated with a marked development of atherosclerosis in the aorta. Flax seed reduced the development of aortic atherosclerosis by 46% and reduced the PMNL-CL without significantly lowering the serum cholesterol. Flax seed in normocholesterolemic rabbits increased serum total cholesterol and decreased PMNL-CL without significantly affecting the serum TG. Modest dietary flax seed supplementation is effective in reducing hypercholesterolemic atherosclerosis markedly without lowering serum cholesterol. Its effectiveness against hypercholesterolemic atherosclerosis could be due to suppression of enhanced production of OFRs by PMNLs in hypercholesterolemia. Dietary flax seed supplementation could, therefore, prevent hypercholesterolemia-related heart attack and strokes.

Topics: Animals; Aorta; Arteriosclerosis; Cholesterol; Cholesterol, Dietary; Cytokines; Diet, Atherogenic; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Hypercholesterolemia; Lignans; Monocytes; Neutrophils; Oxidative Stress; Plants, Edible; Rabbits; Reactive Oxygen Species; Seeds; Triglycerides