| Diabetes mellitus (DM) is the most common metabolic disease in the world thatis characterized by chronic dysglycemia due to impaired metabolism of glucose andother energy-yielding fuels such as lipids and proteins. The metabolic disorder affectsapproximately4%of the global population, and is expected to increase to5.4%by2025. DM results in a significant economic burden in developed countries, with anestimated12%of the worldwide health care disbursement spent toward treatment andprevention of diabetes.Oxidative stress induced by diabetes leads to lipid peroxidation and tissuedamage including retinopathy,nephropathy, and coronary heart disease. Besideshyperglycemia, elevated lipids level of among diabetics is a significant risk factor forcoronary heart disease. Dyslipidemia or hyperlipidemia represents some of the mostimportant risk factors for cardiovascular morbidity and mortality in DM, which isfound in about40%of diabetics. Worldwide epidemic of diabetes has been pushingthe research community in search of novel treatments and therapeutic targets.Dyslipidemia, a major cardiovascular risk factor, occurs due to altered insulinhomeostasis in diabetics that leads to metabolic syndrome. Lipid-lowering therapy indiabetics can reduce the risk of vascular complications.Despite the great strides that have been made in understanding and managementof diabetes, the disease and disease-related complications are increasingunabated.Traditional medicinal plants and their phytoconstituents play major role inthe management of DM from the beginning of the last century; evidentiallipid-lowering properties of medicinal plants have accumulated. Many scientists havedemonstrated the antihyperlipidemic role of medicinal plants for treatinghyperlipidaemia.The ability of antioxidants to inhibit these complications has raised the possibility of newer therapeutic treatment for diabetic heart diseases. Many classesof dietary components and natural antioxidants have been used to regulate or toreduce plasma lipid concentrations and atherosclerosis risks. Diosgenin (C27H42O3),structurally similar to cholesterol and other steroids ascertain an array of biologicaland pharmacological activities. It has been reported that diosgenin has antimicrobial,antiviral, anti-inflammatory, and antidiabetic properties.Although previously published pre-clinical studies have suggested the mitigatingefficacy of diosgenin in streptozotocin (STZ)-induced diabetic neuropathic rats, thereare no reports for anti-lipimic effect. In this context, we decided to explore thepotential antihyperlipidemic activity of diosgenin. The aim of the present study was toelucidate the mechanism underlying the hypolipidemic action of diosgenin byinvestigating the effect of diosgenin on the brain and heart lipids and hepaticexpression of HMG-CoA mRNA in rats with STZ-induced hyperlipidemia and tocompare the efficacy with glyclazide. The antihyperglycemic effect of diosgenin wascompared with glyclazide, a well-known antioxidant and antihyperglycemic drug.Glyclazide, a sulphonylurea derivative, preferred for antidiabetic therapy due to itsinhibitory nature of pancratic KATP channels, antioxidant property, and lowprevalence of producing severe hypoglycemia.Methods：1.Induction of DiabetesDM was experimentally induced by STZ2.Experimental DesignGroup I: Control rats.Group II: Diabetic control rats.Group III: Experimentally induced diabetic rats were administered orally withdiosgenin (40mg/kg b.w./rat) in vehicle solution for45days using an intra-gastrictube.Group IV: Experimentally induced diabetic rats were administered withglyclazide (5mg/kg b.w./rat) in aqueous solution orally for45days. 3.Body weight and the blood glucose levels were assessed periodically. At theend of study, all rats were sacrificed to collect the blood samples， Plasma albumin,ferritin, bilirubin, insulin, transferrin, and ferritin were assayed.4.Extraction of Lipids,Estimation of Cholesterol,Triglycerides,Phospholipids andFree FattyAcids in brain And heart.5.Estimation of HMG-CoAReductaseActivity6.Analysis of mRNAExpression7.HE staining of Heart and brain tissue sections8.Statistical Analysis：All the results were expressed as the mean±SD for sixanimals in each group. All the grouped data were statistically evaluated with SPSS10.0software. Hypothesis testing methods included one-way analysis of variance(ANOVA) followed by least significant difference (LSD)test, significance level atP<0.05,0.01,0.001were considered to indicate statistical significance.Results1.Level of Blood Glucose and Plasma Insulin:blood glucose level of Group1：7.2±1.95mmol/L,Plasma Insulin level of Group1：20.73±3.67μU/ml；blood glucoselevel of Group2：22.82±6.82mmol/L， Plasma Insulin level of Group2：9.42±4.89μU/ml；blood glucose level of Group3：10.28±4.86mmol/L，Plasma Insulinlevel of Group3：18.78±5.39μU/ml； blood glucose level of Group4：8.03±3.45mmol/L，Plasma Insulin level of Group4：19.9±6.51μU/ml。Statisticallysignificant (P<0.05) elevation in blood glucose level with significant decrease inplasma insulin levels was observed in STZ-induced diabetic animals,compared withcontrol animals. However, treatment with diosgenin and glyclazide reduced the bloodglucose and increased plasma insulin to near normal levels.2.Level of Cholesterol，Triglycerides，Phospholipids and Free Fatty Acids inbrain:Level of Cholesterol in brain of Group1：3.37±0.67mg/dl，Level of Cholesterolin brain of Group2：8.42±2.15mg/d，Level of Cholesterol in brain of Group3：5.07±2.27mg/dl，Level of Cholesterol in brain of Group4：5.37±1.3mg/dl；Level ofTriglycerides in brain of these4Groups were14.45±1.59mg/dl，9.82±3.26mg/dl， 4.98±1.81mg/dl，4.55±2.05mg/dl；Level of Phospholipids in brain were9.63±2.55mg/dl，19.54±2.48mg/dl，10.69±2.83mg/dl，10.72±3.2mg/dl；Level of FreeFatty Acids in brain were5.78±1.8mg/dl，10.8±1.24mg/dl，6.85±2.58mg/dl，6.94±1.76mg/dl.3.Level of Cholesterol in heart of Group1：13.47±4.66mg/g tissue， Group2：26.25±6.33mg/g tissue， Group3：16.93±4.52mg/g tissue， Group4：16.32±4.37mg/g tissue；Level of Triglycerides in heart of these4Groups were4.85±1.98mg/dl，11.46±2.39mg/dl，6.55±2.17mg/g tissue，6.44±2.32mg/g tissue；Level ofPhospholipids were25.35±5.45mg/g tissue，36.77±4.28mg/g tissue，27.68±6.1mg/gtissue，26.87±4.6mg/g tissue；Level of Free Fatty Acids were3.49±1.88mg/g tissue，10.9±3.72mg/g tissue，5.09±2.15mg/g tissue，5.69±3.13mg/g tissue。The levels of lipids (total cholesterol, FFAs, TGs, and PLs)in brain and heart ofcontrol and experimental rats are shown in Tables3and4. The concentrations of thebrain and heart lipids (total cholesterol, FFAs, TGs, and PLs)were significantlyincreased in diabetic rats as compared to the normal rats. Treatment with diosgeninsignificantly (P<0.05) reduced the concentrations of the brain and heart lipids (totalcholesterol, FFAs, TGs, and PLs) in diabetic rats to near normal level.4.Effect of Diosgenin Treatment on Activity of Hepatic:HMG-CoA ReductaseThe activities of hepatic HMGR in control and experimental rats are shown in Fig.1.Liver of STZ-treated rats showed significant elevation (55.7%,P<0.001) in HMGRactivity. Administration of diosgenin to diabetic rats significantly reduced HMGRactivity. The effects of diosgenin treatment on HMGR mRNA levels in the liver wereexamined by real-time PCR. The levels of HMGR mRNA was found to be increasedin diabetic control rats.However, diosgenin treatment significantly decreased liverHMGR mRNAlevels.5.Effect of Diosgenin in Heart:Normal architecture of the myocardium wasobserved with no evidence of microscopic changes in the control group animals.Thecardiac sections of the STZ-treated animals revealed increased interstitial space anddistort the intercalated disk. Diosgenin and gliclazide treatment exerted a protective effect as evident by appearance of normal interstitial space and intercalated disk.6.Effect of Diosgenin in Brain:Normal euchromatic nucleus, basophilic cytosol,axon, and dendritis of normal multipolar neurons were observed in control groupanimals. Neuronal necrosis areas were observed in STZ-treated group.Diosgenin andgliclazide administered animals showed normal heterochromatic nucleus structure ofneuroglia cells.Conclusion1Lipid Profile Anomalies in the Heart and Brain occurred in STZ inducedDiabetes rats2DiosgeninAttenuated the Lipid ProfileAnomalies in the Heart and Brain3Liver HMGR activity significant elevated in STZ-treated rats,which can beAttenuated by Administration of diosgenin.4Diosgenin acted protective effect on the significant cell damage in the cardiacand brain of the STZ-treated animals,which can be observed in the HE staining tissuesections. |
PDF Full Text Request