secoisolariciresinol-diglucoside and Body-Weight

Hypercholesterolemia is a risk factor for cardiovascular disease. Conventional treatment methods include lifestyle changes and pharmaceutical interventions, but recently Health Canada approved a health claim for whole ground flaxseed as an alternative treatment for hypercholesterolemia. The literature suggests flaxseed lignans are responsible for the cholesterol-reducing effects of flaxseed. In this study, 96.1% secoisolariciresinol diglucoside (SDG) and a 50% SDG enriched polymer (SDG polymer) were investigated as treatments for hypercholesterolemia in rats. Wistar female rats were fed a 1% high-cholesterol diet for a one-week acclimatization prior to a 23-day intervention with enriched SDG or SDG polymer. A reduction in body weight normalized liver weight was observed in rats treated with enriched SDG when compared to the controls. Both enriched SDG (96.1%) and SDG polymer reduced serum triacylglycerol (19% and 15%, respectively) and increased high-density lipoprotein cholesterol (15% and 24%, respectively). Histopathologic analyses revealed lipid-lowering effects of either enriched SDG or SDG polymer along with lower steatosis scores and nonalcoholic fatty liver disease activity. Furthermore, the lack of statistical significance between SDG and SDG polymer treatment groups suggests that SDG polymer may be a potential alternative to enriched SDG for hypercholesterolemia with similar efficacy but lower cost.

Topics: Animals; Anticholesteremic Agents; Body Weight; Butylene Glycols; Female; Glucosides; Lipids; Liver; Organ Size; Polymers; Rats; Rats, Wistar

Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been associated with a lower incidence of cardiovascular events and sudden cardiac death. Flaxseed is a rich plant source of n-3 PUFAs and can retard the progression and accelerate the regression of atherosclerotic plaques. The aim of the study was to examine the preventive and therapeutic effects of dietary flaxseed on arrhythmias and heart dysfunction that develops after a myocardial infarction (MI). The left anterior descending coronary artery was ligated in rats to induce the MI. Rats were randomized into five groups: sham MI with normal chow, MI with normal chow, MI with 10% milled flaxseed supplementation (flax), MI with 4.4% supplemented flax oil enriched in alpha-linolenic acid (ALA) and MI with flax lignan secoisolariciresinol diglucoside (SDG) supplementation (0.44%). Animals were fed with their respective diets for 2 weeks before and for 8 weeks after the surgery. Echocardiography and continuous electrocardiographic recordings were obtained after ligation to confirm the induction of the MI, to check for arrhythmias and to assess cardiac function. Histological examination was also performed to evaluate cardiac fibrosis. Dietary supplementation with flaxseed, ALA or SDG before and after the induction of the MI significantly reduced the incidence of arrhythmias and resulted in significantly smaller infarct size, less left ventricle dilation, and decreased myocardial fibrosis and tumor necrosis factor-α levels compared to the control MI group. Together, this study supports a beneficial effect of dietary flaxseed in patients for the prevention and treatment of arrhythmias and ventricular remodeling post-MI.

Topics: alpha-Linolenic Acid; Animals; Arrhythmias, Cardiac; Body Weight; Butylene Glycols; Cardiotonic Agents; Dietary Supplements; Electrocardiography; Fatty Acids; Flax; Glucosides; Male; Myocardial Infarction; Myocarditis; Organ Size; Rats, Sprague-Dawley; Ventricular Remodeling

This study evaluated the protective effect of flaxseed oil (FO) and flaxseed lignan secoisolariciresinol diglucoside (SDG) against oxidative stress in rats with metabolic syndrome (MS). 48 rats were allocated into the following 6 groups: Groups 1 (control), 5 (FO), and 6 (SDG) received water and were treated daily orally with saline, FO, and SDG, respectively. Groups 2 (MS), 3 (MS+FO), and 4 (MS+SDG) received 30% fructose in drinking water for MS induction and were treated daily orally with saline, FO, and SDG, respectively. After 30 d, animals were sacrificed, and blood was collected for biochemical and oxidative analysis. Body weight was recorded weekly. Systolic blood pressure (SBP) was measured before and after treatment. Fructose could produce MS and oxidative stress. FO and SDG prevented changes in SBP, lipids, and glucose. FO and SDG prevented oxidative damage to lipids, and only FO prevented oxidative damage to proteins associated to MS. FO and SDG improved enzymatic antioxidants defenses and reduced glutathione levels, which was greater with SDG. Total polyphenol levels were enhanced in groups that received SDG. Thus, the results of this study demonstrated that treatment with a 30% fructose solution for 30 d is effective for MS induction and the oxidative stress is involved in the pathophysiology of MS induced by fructose-rich diets. Furthermore, we demonstrated that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content especially that of SDG, suggesting that this compound can be used in isolation to prevent oxidative stress associated with MS.. We report that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content, especially that of secoisolariciresinol diglucoside. This is significant because suggests that this compound can be used in isolation to prevent oxidative stress associated with MS. Furthermore, this study was the only one to perform a comparison of the abilities of 2 components of flaxseed to protect against oxidative stress in an MS model, which brings a great advance in the medicine's field, since it indicates another alternative for improve the health and the quality of life of patients with this disorder.

Topics: Animals; Antioxidants; Body Weight; Butylene Glycols; Flax; Fructose; Glucose; Glucosides; Humans; Lignans; Linseed Oil; Lipids; Male; Metabolic Syndrome; Oxidative Stress; Protective Agents; Quality of Life; Rats

Flaxseed (FS) has a breast tumor-reducing effect, possibly because of its high content of secoisolariciresinol diglucoside (SDG) lignan. Sesame seed (SS) is rich in the lignan sesamin (SES) but is non-protective. Both lignans are metabolized to estrogen-like enterodiol and enterolactone. The objective of this study was to differentiate the effects of SDG and SES on established human estrogen receptor-positive breast tumors (MCF-7) in athymic mice with high serum estrogen to help explain the different effects of FS and SS. Mice were fed for 8 wk the basal diet (BD, control) or BD supplemented with 1 g/kg SDG or SES. SES reduced palpable tumor size by 23% compared to control, whereas SDG did not differ from SES or control. Both treatments reduced tumor cell proliferation, but only SES increased apoptosis. SDG and SES reduced human epidermal growth factor receptor 2 and endothelial growth factor receptor expressions, but only SES reduced downstream pMAPK. Neither treatment affected IGF-1R, vascular endothelial growth factor receptor-2, Akt, pAkt, or MAPK of the growth factor signaling pathway. Thus, at high serum estrogen levels, SDG may not account for the tumor reducing effect of FS. SES was more effective than SDG in reducing breast tumor growth, but its effect may have been lost when consumed as a component of SS.

Topics: Animals; Apoptosis; Body Weight; Breast Neoplasms; Butylene Glycols; Cell Line, Tumor; Cell Proliferation; Dioxoles; Eating; Estrogens; Female; Flax; Glucosides; Humans; Lignans; Mice; Mice, Nude; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Seeds; Sesamum; Signal Transduction; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays

The potential effects of secoisolariciresinol diglucoside lignan-enriched flaxseed powder (LEFP) on bodyweight, visceral fat, lipid profile, adipokines, and blood pressure were investigated using rats, divided into four groups (n=8); a normal control diet (NC), a normal control diet with 0.02% LEFP (NCL), a high-fat and high-fructose diet (HFD), or a high-fat and high-fructose diet with 0.02% LEFP (HFDL). Liver, heart, kidney, adipose tissues, and blood were collected following 12-weeks on the diets. The average body weight of the HFD group was significantly higher than those of the NC, NCL, and the HFDL groups (P<0.05). Also, the average weights of kidneys from the HFD and HFDL groups was higher than those of the NC and NCL groups (P<0.05), although not significantly different in the weights of livers and hearts. The visceral fat weight was significantly higher in rats in the HFD group, but notably reduced in the HFDL fed rats (P<0.05). Accordingly, plasma leptin increased significantly in rats fed the HFD diet, higher than rats fed the HFDL diet. Also, the rats in the HFDL group showed improved lipid profile, compared to the rats in the HFD group (P<0.05). Furthermore, a significant reduction in blood pressure was observed in the rats of the HFDL group compared to the HFD group (P<0.05). These data suggest that the LEFP supplementation may provide beneficial effects such as the reduction of bodyweight and fat accumulation, the lipid profile improvement, and blood pressure control.

Topics: Animals; Blood Pressure; Body Weight; Butylene Glycols; Diet, High-Fat; Dietary Fats; Dietary Sucrose; Flax; Food, Fortified; Fructose; Glucosides; Heart; Intra-Abdominal Fat; Kidney; Leptin; Lipids; Liver; Male; Organ Size; Rats; Rats, Sprague-Dawley; Seeds

The present study involved a comparative analysis of the effects of purified flaxseed lignans, secoisolariciresinol diglucoside (SDG) and its aglycone metabolite (SECO), in hyperlipidaemic rats. For hypercholesterolaemia, female Wistars (six rats per group) were fed a standard or 1 % cholesterol diet and orally administered 0, 3 or 6 mg SDG/kg or 0, 1.6 or 3.2 mg SECO/kg body weight once daily for 4 weeks. Hypertriacylglycerolaemia was induced in male Sprague-Dawley rats (ten rats per group) by supplementing tap water with 10 % fructose. These rats were orally administered 0, 3 or 6 mg SDG/kg body weight once daily for 2 weeks. Fasting blood samples (12 h) were collected predose and at the end of the dosing period for serum lipid analyses. Rats were killed and livers rapidly excised and sectioned for lipid, mRNA and histological analyses. Chronic administration of equimolar amounts of SDG and SECO caused similar dose-dependent reductions in rate of body-weight gain and in serum total and LDL-cholesterol levels and hepatic lipid accumulation. SDG and SECO failed to alter hepatic gene expression of commonly reported regulatory targets of lipid homeostasis. SDG had no effect on serum TAG, NEFA, phospholipids and rate of weight gain in 10 % fructose-supplemented rats. In conclusion, our data suggest that the lignan component of flaxseed contributes to the hypocholesterolaemic effects of flaxseed consumption observed in humans. Future studies plan to identify the biochemical mechanism(s) through which flaxseed lignans exert their beneficial effects and the lignan form(s) responsible.

Topics: Animals; Base Sequence; Body Weight; Butylene Glycols; Dose-Response Relationship, Drug; Female; Flax; Fructose; Gene Expression; Glucosides; Hyperlipidemias; Lignans; Lipids; Liver; Male; Models, Animal; Molecular Sequence Data; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar

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

Flaxseed's oil and lignan, secoisolariciresinol diglucoside (SDG), are implicated in attainment of health and treatment of renal injury and osteoporosis. To test for these benefits, weanling Han:SPRD-cy rats (n=171) with or without kidney disease were randomized to diets made with either corn oil or flaxseed oil and with or without SDG for 12 weeks. In females, weight was lower with the SDG diet. In males fed flaxseed oil, lean mass was higher and fat % was lower. In both sexes, fat % was lower in diseased rats. Bone mineral content (BMC) and density were higher in rats fed flaxseed oil and lower in diseased rats, additionally; BMC was lower in SDG-supplemented females. The benefit of flaxseed oil on body composition is sex specific but the effect on bone mass is not. Lastly, reduced weight due to early rat kidney disease is not due to loss of lean body mass.

Topics: Animals; Body Weight; Bone Density; Butylene Glycols; Corn Oil; Dietary Fats; Female; Glucosides; Kidney Diseases; Linseed Oil; Male; Random Allocation; Rats; Rats, Inbred Strains

Previous studies have shown that feeding flaxseed (FS) or its lignan secoisolariciresinol diglucoside (SDG) to rat dams during lactation enhances the differentiation of rat mammary gland in the female offspring. This study determined whether exposure to a diet with 10% FS or SDG (equivalent to the amount in 10% FS) during suckling could protect against 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced rat mammary tumorigenesis later in life. Dams were fed the AIN-93G basal diet (BD) throughout pregnancy. After delivery, dams were randomized to continue on BD or were fed BD supplemented with 10% FS or SDG during lactation. Three-day urine of dams was analyzed for mammalian lignans. After weaning, all offspring were fed BD. At postnatal Days 49 to 51, during proestrus phase, offspring were gavaged with 5 mg of DMBA. At Week 21 post-DMBA administration, compared with the BD group, the FS and SDG groups had significantly lower (P < 0.05) tumor incidence (31.3% and 42.0% lower, respectively), total tumor load (50.8% and 62.5% lower, respectively), mean tumor size (43.9% and 67.7% lower, respectively), and tumor number (46.9% and 44.8% lower, respectively) per rat. There was a significant decreasing trend (P < 0.05) in final tumor weights in rats fed FS or SDG. The high urinary lignan excretion in dams fed with FS or SDG corresponded with the reduced tumor development. The FS and SDG groups did not differ significantly in tumor indices, indicating that the effect of FS is primarily due to its SDG. There were no significant changes in selective reproductive indices measured among dams and offspring. In conclusion, exposure to FS or SDG during suckling suppressed DMBA-induced rat mammary tumorigenesis, suggesting that exposure to lignans at this early stage of mammary gland development reduces susceptibility to mammary carcinogenesis later in life without adverse effects on selective reproductive indices in dams or offspring.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Animals, Suckling; Body Weight; Butylene Glycols; Carcinogens; Diet; Disease Models, Animal; Female; Flax; Glucosides; Lactation; Lignans; Mammary Neoplasms, Experimental; Rats; Rats, Sprague-Dawley; Reproduction

Flaxseed and its lignan secoisolariciresinol diglycoside (SDG) inhibit mammary tumor development in rats. Increased plasma insulin-like growth factor I (IGF-I) concentrations are associated with increased breast cancer risk. Therefore, the effect of flaxseed (5%) or SDG (1.5 mg/day) supplementation on plasma IGF-I levels was examined in rats treated with or without N-methyl-N-nitrosourea (MNU). In MNU-free rats, flaxseed and SDG reduced plasma IGF-I levels, which were inversely related to urinary lignan excretion. Only flaxseed significantly reduced plasma IGF-I concentrations in MNU-treated rats. The anticancer effect of flaxseed and SDG may be related, in part, to reductions in plasma IGF-I.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Butylene Glycols; Carcinogens; Dietary Supplements; Eating; Female; Flax; Glucosides; Insulin-Like Growth Factor I; Lignans; Mammary Glands, Animal; Methylnitrosourea; Organ Size; Rats; Rats, Sprague-Dawley

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.. 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 approximately 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%.. 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.

Topics: Animals; Aortic Diseases; Arteriosclerosis; Body Weight; Butylene Glycols; Cholesterol; Cholesterol, LDL; Diet, Atherogenic; Glucosides; Hypercholesterolemia; Lipid Peroxidation; Lipoproteins; Luminescent Measurements; Malondialdehyde; Rabbits; Seeds; Triglycerides

Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk. This study determined whether over the long term flaxseed still exerts a colon cancer protective effect, whether its effect may, in part, be due to its high content of SD and whether any change in beta-glucuronidase activity plays a role in the protective effect. Six groups of male Sprague-Dawley rats were fed for 100 days either a basal high fat (20%) diet (BD), BD supplemented with 2.5 or 5% flaxseed or 2.5 or 5% defatted flaxseed (equivalent to the respective flaxseed diets) or BD with a daily gavage of 1.5 mg SD. All rats were injected with a single dose of azoxymethane (15 mg/kg body wt) 1 week prior to commencing the dietary treatments. Urinary lignan excretion, which is an indicator of mammalian lignan production, was significantly increased in the flaxseed and defatted flaxseed groups. The total activity of cecal beta-glucuronidase was significantly increased in a dose-dependent manner by the flaxseed and defatted flaxseed diet groups. Compared with the control the number of aberrant crypts per focus was significantly reduced in the distal colon of the treated rats. Four microadenomas and two polyps were observed in the control group, but not in the treated groups. The total activity of beta-glucuronidase was positively correlated with total urinary lignan excretion and negatively with the total number of aberrant crypts and the total number of aberrant crypt foci in the distal colon. There were no significant differences between the flaxseed and the corresponding defatted flaxseed groups. It is concluded that flaxseed has a colon cancer protective effect, that it is due, in part, to SD and that the protective effect of flaxseed is associated with increased beta-glucuronidase activity.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Butylene Glycols; Cecum; Colonic Neoplasms; Eating; Fatty Acids; Glucosides; Glucuronidase; Hydrogen-Ion Concentration; Lignans; Male; Organ Size; Plant Extracts; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Seeds