secoisolariciresinol-diglucoside and Hyperglycemia

There is increased risk of colon cancer in both men and women having diabetes. The objective of the study was to evaluate the role of Secoisolariciresinol diglucoside rich extract(SRE) of L.usissatisimum(flaxseed) in colon cancer associated with type 2 diabetes mellitus.. Diabetes was induced by administering high fat diet with low dose streptozotocin model. After 6 weeks, diabetes was confirmed and 1,2 dimethylhydrazine(25mg/kg, sc) weekly administration was from 6th to 18th weeks. Rats were treated with the SRE(500mg/kg) orally from 6th to 24th week. After 24 weeks, various biochemical and enzymatic parameters were estimated. Animals were sacrificed and colon tissue was separated and subjected to analysis of histopathological, PCNA studies and mRNA expression of CDK4.. Disease control rats depicted hyperglycaemia, hyperinsulinaemia, elevated pro-inflammatory cytokines and cancer biomarker levels, and marked presence of proliferating cells. Treatment with SRE controlled hyperglycaemia, hyperinsulinaemia, reduced pro-inflammatory cytokines and cancer biomarker levels, and decreased no. of proliferating cells. We found that disease control rats depicted over expression of CDK4 mRNA levels which were reduced by SRE treatment.. SRE of L. usitatissimum exhibited chemopreventive effect in colon cancer associated with type 2 diabetes mellitus which might be mediated through inhibition of CDK4.

Topics: Animals; Biomarkers, Tumor; Butylene Glycols; Cell Proliferation; Colonic Neoplasms; Cyclin-Dependent Kinase 4; Cytokines; Diabetes Mellitus, Type 2; Female; Flax; Gene Expression Regulation, Neoplastic; Glucose Tolerance Test; Glucosides; Hyperglycemia; Inflammation Mediators; Male; Phytochemicals; Plant Extracts; Proliferating Cell Nuclear Antigen; Rats, Sprague-Dawley; RNA, Messenger

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to oxidative stress and if SDG can prevent the incidence of diabetes. The rats were divided into three groups: Group I, BioBreeding normal rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was determined by measuring lipid peroxidation product malondialdehyde (MDA) an index of level of reactive oxygen species in blood and pancreas; and pancreatic chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by glycosuria and hyperglycemia. SDG prevented the development of diabetes by approximately 71%. Development of diabetes was associated with an increase in serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in development of diabetes by SDG was associated with a decrease in serum and pancreatic-MDA and an increase in antioxidant reserve. These results suggest that IDDM is mediated through oxidative stress and that SDG prevents the development of diabetes.

Topics: Animals; Butylene Glycols; Diabetes Mellitus, Type 1; Glucosides; Glycosuria; Humans; Hyperglycemia; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; Pancreas; Rats; Rats, Inbred BB; Reactive Oxygen Species