lignans and Hypercholesterolemia

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

Several clinical trials have investigated the effects of flaxseed and flaxseed-derived products (flaxseed oil or lignans) on blood lipids; however, the findings have been inconsistent.. We aimed to identify and quantify the effectiveness of flaxseed and its derivatives on blood lipid profiles.. A comprehensive literature search was performed on the basis of English reports of randomized controlled trials of flaxseed or its derivatives on lipid profiles in adults, which were published from January 1990 to October 2008. Attempts also were made to access unpublished data. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted.. Twenty-eight studies were included. Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), respectively; significant reductions were observed with whole flaxseed (-0.21 and -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) supplements but not with flaxseed oil. The cholesterol-lowering effects were more apparent in females (particularly postmenopausal women), individuals with high initial cholesterol concentrations, and studies with higher Jadad scores. No significant changes were found in the concentrations of HDL cholesterol and triglycerides.. Flaxseed significantly reduced circulating total and LDL-cholesterol concentrations, but the changes were dependent on the type of intervention, sex, and initial lipid profiles of the subjects. Further studies are needed to determine the efficiency of flaxseed on lipid profiles in men and premenopausal women and to explore its potential benefits on other cardiometabolic risk factors and prevention of cardiovascular disease.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Flax; Humans; Hypercholesterolemia; Lignans; Linseed Oil; Lipid Metabolism; Male; Randomized Controlled Trials as Topic; Seeds; Treatment Outcome; Triglycerides

Hormone replacement therapy has traditionally been used to treat the accompanying symptoms of oestrogen deficiency in menopause. However, not all women can, or prefer to, receive this treatment and alternatives should be considered to reduce the increased risk of osteoporosis and heart disease in menopausal women. This chapter reviews the current literature on the efficacy of phyto-oestrogens in preventing cardiovascular disease, various cancers and osteoporosis, as well as treating the vasomotor and other menopause-related symptoms. Select herbal therapies, as well as selective oestrogen receptor modulators, are also considered.

Topics: Cardiovascular Diseases; Estrogens; Female; Humans; Hypercholesterolemia; Isoflavones; Lignans; Menopause; Middle Aged; Neoplasms; Osteoporosis, Postmenopausal; Phytotherapy; Plant Preparations; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators

The objective of the present study was to compare whole pea flour (WPF) to fractionated pea flour (FPF; hulls only) for their ability to reduce risk factors associated with CVD and diabetes in overweight hypercholesterolaemic individuals. Using a cross-over design, twenty-three hypercholesterolaemic overweight men and women received two-treatment muffins/d containing WPF, FPF or white wheat flour (WF) for 28 d, followed by 28 d washout periods. Daily doses of WPF and FPF complied with the United States Department of Agriculture's recommended level of intake of half a cup of pulses/d (approximately 50 g/d). Dietary energy requirements were calculated for each study subject, and volunteers were only permitted to eat food supplied by the study personnel. Fasting insulin, body composition, urinary enterolactone levels, postprandial glucose response, as well as fasting lipid and glucose concentrations, were assessed at the beginning and at the end of each treatment. Insulin concentrations for WPF (37·8 (SEM 3·4) pmol/ml, P = 0·021) and FPF (40·5 (SEM 3·4) pmol/ml, P = 0·037) were lower compared with WF (50·7 (SEM 3·4) pmol/ml). Insulin homeostasis modelling assessment showed that consumption of WPF and FPF decreased (P < 0·05) estimates of insulin resistance (IR) compared with WF. Android:gynoid fat ratios in women participants were lower (P = 0·027) in the WPF (1·01 (sem 0·01) group compared with the WF group (1·06 (SEM 0·01). Urinary enterolactone levels tended to be higher (P = 0·087) in WPF compared with WF. Neither treatment altered circulating fasting lipids or glucose concentrations. In conclusion, under a controlled diet paradigm, a daily consumption of whole and fractionated yellow pea flours at doses equivalent to half a cup of yellow peas/d reduced IR, while WPF reduced android adiposity in women.

Topics: 4-Butyrolactone; Adiposity; Adult; Body Composition; Cardiovascular Diseases; Cross-Over Studies; Diabetes Mellitus; Fasting; Female; Flour; Humans; Hypercholesterolemia; Insulin; Insulin Resistance; Lignans; Male; Middle Aged; Overweight; Phytotherapy; Pisum sativum; Plant Preparations; Risk Factors; Seeds

The effects of flaxseed lignan (secoisolariciresinol diglucoside [SDG]) intake on hypercholesterolemia and liver disease risk factors in moderately hypercholesterolemic men were investigated. In a previous study, we reported that SDG attenuates high-fat, diet-induced hypercholesterolemia in mice. Here, we report a double-blinded, randomized, and placebo-controlled study in moderately hypercholesterolemic men in which we investigated the hypothesis that oral administration of SDG (20 or 100 mg) would decrease the level of blood cholesterol and liver disease risk factors induced by hypercholesterolemia in humans. Thirty men with total cholesterol levels of 4.65 to 6.21 mmol/L (180-240 mg/dL) were randomly assigned to 3 groups; 2 groups received flaxseed lignan capsules (SDG, 20 or 100 mg/d) and the other received placebo capsules for 12 weeks. We found that, compared to the subjects who received placebo, those who received 100 mg of SDG exhibited a significant reduction in the ratio of low-density lipoprotein/high-density lipoprotein cholesterol at baseline (P < .05) and at week 12 (P < .05). In addition, in SDG-treated subjects, we also observed a significant percentage decrease in the levels of glutamic pyruvic transaminase and gamma-glutamyl transpeptidase relative to the levels at baseline (P < .01) and a significant percentage decrease in the level of gamma-glutamyl transpeptidase relative to the placebo-treated group (P < .05). These results suggest that daily administration of 100 mg SDG can be effective at reducing blood level of cholesterol and hepatic diseases risk in moderately hypercholesterolemic men.

Topics: Adult; Anthropometry; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Flax; Humans; Hypercholesterolemia; Lignans; Liver Diseases; Male; Metabolic Syndrome; Middle Aged; Phytotherapy; Placebos; Plant Extracts; Risk Factors

The study objectives were to examine total and individual lignan intakes and their dietary sources in postmenopausal Polish women and to investigate the relationship between lignan intake and the prevalence of cardiovascular disease (CVD), hypertension, hypercholesterolemia and central obesity. A total of 2599 postmenopausal women, participants of the Multi-centre National Population Health Examination Surveys (WOBASZ and WOBASZ II) were selected. Of them, 916 had a history of CVD. Nutritional data were collected using a single 24-h dietary recall. Data on lignan content in food, i.e., lariciresinol (LARI), matairesinol (MAT), pinoresinol (PINO) and secoisolariciresinol (SECO), were collected from the available lignan databases. In postmenopausal women, total and individual lignan intakes (SECO, PINO, MAT) were not associated with the prevalence of CVD and its risk factors. The intake of LARI was linked by 30% to the reduced odds for hypercholestrolemia. This study reinforces the existing concept that dietary total lignans are not associated with the prevalence of CVD, and provides further evidence that they are not linked to CVD risk factors such as hypertension, hypercholesterolemia and central obesity. However, the intake of LARI should be taken into consideration in further studies with regard to its potentially beneficial effect in hypercholesterolemia.

Topics: Age Factors; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Diet Surveys; Female; Humans; Hypercholesterolemia; Hypertension; Lignans; Logistic Models; Middle Aged; Obesity, Abdominal; Odds Ratio; Poland; Postmenopause; Prevalence; Protective Factors; Risk Factors; Sex Factors

Sesame seed is rich in sesamin. The present study was to (i) investigate the plasma cholesterol-lowering activity of dietary sesamin and (ii) examine the interaction of dietary sesamin with the gene expression of sterol transporters, enzymes, receptors, and proteins involved in cholesterol metabolism. Thirty hamsters were divided into three groups fed the control diet (CON) or one of two experimental diets containing 0.2% (SL) and 0.5% (SH) sesamin, respectively, for 6 weeks. Plasma total cholesterol (TC) levels in hamsters given the CON, SL, and SH diets were 6.62 ± 0.40, 5.32 ± 0.40, and 5.00 ± 0.44 mmol/L, respectively, indicating dietary sesamin could reduce plasma TC in a dose-dependent manner. Similarly, the excretion of total fecal neutral sterols was dose-dependently increased with the amounts of sesamin in diets (CON, 2.65 ± 0.57; SL, 4.30 ± 0.65; and SH, 5.84 ± 1.27 μmol/day). Addition of sesamin into diets was associated with down-regulation of mRNA of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporters subfamily G members 5 and 8 (ABCG5 and ABCG8). Results also showed that dietary sesamin could up-regulate hepatic cholesterol-7α-hydroxylase (CYP7A1), whereas it down-regulated hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and liver X receptor alpha (LXRα). It was concluded that the cholesterol-lowering activity of sesamin was mediated by promoting the fecal excretion of sterols and modulating the genes involved in cholesterol absorption and metabolism.

Topics: Animals; Anticholesteremic Agents; ATP-Binding Cassette Transporters; Biological Transport; Carrier Proteins; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cricetinae; Dioxoles; Down-Regulation; Humans; Hypercholesterolemia; Intestinal Mucosa; Intestines; Lignans; Liver X Receptors; Male; Mesocricetus; Orphan Nuclear Receptors; Sterol O-Acyltransferase; Sterol O-Acyltransferase 2

Schisandra, a globally distributed plant, has been widely applied to health care products. Here, we investigated the effects of dietary intake of Fructus Schisandrae chinensis (FSC), both aqueous and ethanolic extracts (AqFSC, EtFSC), on serum/hepatic lipid contents in normal diet (ND)- and high-fat/cholesterol/bile salt diet (HFCBD)-fed mice.. Male ICR mice were fed with ND or HFCBD, supplemented with 1 and 4% of AqFSC and EtFSC, respectively, or 0.1% fenofibrate, for 13 days. Lipids were determined according to the manufacture's instructions.. EtFSC, but not AqFSC, significantly elevated hepatic triglyceride (TG) in mice fed with ND. Feeding mice with HFCBD increased serum total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) levels as well as alanine aminotransferase (ALT) activity. Supplementation with AqFSC, EtFSC or fenofibrate significantly reduced hepatic TC and TG levels. However, AqFSC and EtFSC supplementation increased serum HDL and LDL levels in mice fed with HFCBD. Fenofibrate increased serum HDL and reduced serum LDL contents in hypercholesterolemic mice. EtFSC reduced, but fenofibrate elevated, serum ALT activity in both normal and hypercholesterolemic mice. While fenofibrate reduced serum TC, TG, and HDL levels in mice fed with ND, it increased serum HDL and reduced serum LDL and TC levels in mice fed with HFCBD. Hepatomegaly was found in normal and hypercholesterolemic mice fed with diet supplemented with fenofibrate.. Feeding mice with AqFSC and EtFSC ameliorated the HFCBD-induced hepatic steatosis. In addition, EtFSC may offer protection against hepatic injury in hypercholesterolemic mice.

Topics: Animals; Cyclooctanes; Diet; Drugs, Chinese Herbal; Fenofibrate; Fruit; Hypercholesterolemia; Hypolipidemic Agents; Lignans; Lipid Metabolism; Lipids; Liver; Mice; Polycyclic Compounds; Triglycerides

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.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Aorta; Atherosclerosis; Body Weight; Disease Models, Animal; Disease Progression; Flax; Hypercholesterolemia; Leukocytes; Lignans; Lipids; Malondialdehyde; Oxidative Stress; Rabbits; Time Factors

The effects of schisandrin B (Sch B) on liver and serum lipid contents were investigated in mice with experimentally-induced hypercholesterolaemia. Hypercholesterolaemia was induced either by oral administration of a cholesterol/bile salts mixture (2/0.5 g kg(-1)) for four days or by feeding a high fat/cholesterol/bile salts (10/1/0.3%, w/w) diet for seven days. Daily co-administration of Sch B (50-200 mg kg(-1), i.g.) for four or six days, respectively, decreased hepatic total cholesterol (TC) and triglyceride (TG) levels (by up to 50% and 52%, respectively) in hypercholesterolaemic mice. Sch B treatment also increased hepatic indices (14-84%) in hypercholesterolaemic mice. The results indicated that Sch B treatment could decrease hepatic TC and TG levels, and increase liver weight, in mouse models of hypercholesterolaemia. Fenofibrate treatment (100 mg kg(-1)) produced effects similar to those of Sch B on the hepatic index and lipid levels of hypercholesterolaemic mice.

Topics: Animals; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Cyclooctanes; Disease Models, Animal; Dose-Response Relationship, Drug; Fatty Liver; Fenofibrate; Hypercholesterolemia; Hypolipidemic Agents; Lignans; Liver; Male; Mice; Mice, Inbred ICR; Polycyclic Compounds; Schisandra; Triglycerides

Flax lignan complex (FLC) isolated from flaxseed suppresses the development of hypercholesterolemic atherosclerosis. The objectives of this study were to investigate if FLC produces regression of atherosclerosis and if regression is associated with reductions in serum lipids and oxidative stress. The studies were conducted in 4 groups of rabbits: group I, control diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (2 months) followed by regular diet (4 months); and group IV, 0.25% cholesterol diet (2 months) followed by regular diet and FLC (4 months). Serum lipids and oxidative stress parameters were measured before and at various intervals thereafter on their respective diets. The aortas were removed at the end of the protocol for assessment of atherosclerotic plaques and oxidative parameters. Atherosclerosis in group II was associated with hyperlipidemia and increased oxidative stress. Atherosclerotic changes were accelerated in group III, and this was associated with reductions in serum lipids and oxidative stress. Atherosclerotic lesions in group IV were similar to group II, but significantly smaller than those in group III, and were associated with reductions in serum lipids and oxidative stress similar to that in group III. These results indicate that FLC does not produce regression but prevents the acceleration of atherosclerosis due to the removal of cholesterol in the diet. These effects of FLC are not associated with reductions in serum lipids and oxidative stress.

Topics: Analysis of Variance; Animals; Antioxidants; Aorta; Atherosclerosis; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Disease Models, Animal; Flax; Hypercholesterolemia; Lignans; Luminescent Measurements; Malondialdehyde; Oxidative Stress; Phytotherapy; Plant Extracts; Rabbits

Phytoestrogens have been suggested to lower cardiovascular disease risk, but existing research focused on non-Western high intake levels and on risk factors. We investigated whether habitual low phytoestrogen intake is associated with manifest cardiovascular disease risk.. Between 1993 and 1997, 16,165 women 49 to 70 years old and free from cardiovascular disease were enrolled in the Dutch Prospect-EPIC cohort (European Prospective study Into Cancer and nutrition) and followed up for a median period of 75 months. At enrollment, women filled in questionnaires on chronic disease risk factors and nutrition. Intake of phytoestrogens was estimated using the food frequency questionnaire covering regular dietary intake of 178 food items in the year before enrollment. Cox regression analysis was used to estimate hazard ratios of cardiovascular disease for quartiles of phytoestrogen intake adjusted for age at intake, body mass index, smoking, physical activity, hypertension, hypercholesterolemia, use of hormone replacement therapy, menopausal status, and intake of total energy, total fiber, vegetables, fruit, and alcohol. In total, 372 women experienced a coronary event (CHD) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9], 410 to 414, 427.5) and 147 women a cerebrovascular event (CVD) (ICD-9, 430 to 438) during follow-up. Overall, neither isoflavones nor lignans were associated with decreased cardiovascular disease risk. When stratifying for ever versus never smokers, CHD risk decreased with increasing lignan intake for ever smokers.. Our results do not support the presence of a protective effect of higher intake of phytoestrogens in low doses on cardiovascular disease risk, although a small risk reduction with higher lignan intake cannot be excluded for smokers.

Topics: Aged; Alcohol Drinking; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Follow-Up Studies; Fruit; Hormone Replacement Therapy; Humans; Hypercholesterolemia; Hypertension; Isoflavones; Lignans; Menopause; Middle Aged; Netherlands; Nutrition Surveys; Phytoestrogens; Proportional Hazards Models; Prospective Studies; Risk; Smoking; Stroke; Surveys and Questionnaires; Vegetables

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

Plant glucosides possess antioxidative properties due to their ability to scavenge free radicals. Sesame seeds contain a class of these compounds, the sesaminol glucosides. To evaluate their antioxidative activity in vivo, we fed rabbits diets containing 1% cholesterol (Chol) with or without 10% defatted sesame flour (DSF) (containing 1% sesaminol glucosides) for 90 d. We determined the susceptibility of their tissues to oxidation ex vivo as well as serum total cholesterol (TC), phospholipid (PL), triglyceride (TG) and HDL cholesterol (HDL-C) concentrations. Serum TC, HDL-C, PL and TG levels were unaffected by the addition of DSF. The HDL-C in the Chol + DSF group was greater than in the Chol group at 45 d. Both were greater than in the groups that did not consume cholesterol. Liver TC and TG were significantly lower in rabbits fed the diet containing DSF plus 1% cholesterol than in those fed 1% cholesterol alone. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances (TBARS), was lower in the liver (P < 0.05) and serum (P = 0.06) of rabbits fed DSF plus cholesterol than in rabbits fed the cholesterol diet. Although we did not detect sesaminol glucosides in peripheral tissues, we observed abundant quantities of sesaminol in rabbits fed DSF, the principal metabolite. Our findings suggest that feeding DSF to rabbits does not protect cholesterol-induced hypercholesterolemia, but may decrease susceptibility to oxidative stress in rabbits fed cholesterol, perhaps due to the antioxidative activity of sesaminol.

Topics: Analysis of Variance; Animals; Anticholesteremic Agents; Antioxidants; Body Weight; Cholesterol, Dietary; Cholesterol, LDL; Chromatography, High Pressure Liquid; Dietary Fats; Dioxoles; Flour; Furans; Hypercholesterolemia; Lignans; Lipid Peroxidation; Liver; Male; Organ Size; Oxidative Stress; Rabbits; Vitamin E

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

1. Effects of sesamin and episesamin (an epimer of sesamin) on lipid metabolism, in particular cholesterol metabolism, were examined in normocholesterolaemic and hypercholesterolaemic stroke-prone spontaneously hypertensive rats (SHRSP). 2. In normocholesterolaemic SHRSP fed a regular diet, both sesamin and episesamin significantly increased the concentration of serum total cholesterol, which was due to an increase of high density lipoprotein (HDL) subfraction rich in apoE (apoE-HDL). In addition, both substances effectively decreased serum very low density lipoprotein (VLDL). In the liver, only episesamin significantly decreased the activity of microsomal acyl-CoA:cholesterol acyltransferase. 3. In hypercholesterolaemic SHRSP fed a high-fat and high-cholesterol diet (HFC diet), only episesamin improved serum lipoprotein metabolism with an increase in apoA-I and a decrease in apoB. In the liver, both sesamin and episesamin significantly suppressed cholesterol accumulation. Interestingly, only episesamin significantly increased the activity of microsomal cholesterol 7alpha-hydroxylase. 4. These results indicate that sesamin may be effective in preventing cholesterol accumulation in the liver. In comparison with sesamin, episesamin may be effective in the regulation of cholesterol metabolism in the serum and liver.

Topics: Animals; Anticholesteremic Agents; Apolipoproteins; Blood Pressure; Cerebrovascular Disorders; Cholesterol; Dioxoles; Hypercholesterolemia; Lignans; Lipid Metabolism; Lipids; Male; Rats; Rats, Inbred SHR; Sterol O-Acyltransferase

Topics: Animals; Dioxoles; Hypercholesterolemia; Lignans; Lipase; Lipoprotein Lipase; Lipoproteins; Male; Rats; Rats, Inbred SHR