Hyperlipidemia In Diabetic Rats Research Articles

Swietenine Alleviates Nonalcoholic Fatty Liver Disease in Diabetic Mice via Lipogenesis Inhibition and Antioxidant Mechanisms.

Our previous studies have reported the effect of swietenine (a major bioactive component of Swietenia macrophylla seeds) in reversing and potentiating the effect of metformin in hyperglycemia and hyperlipidaemia in diabetic rats. Moreover, we reported that the anti-inflammatory effect of swietenine is mediated via the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This study evaluated the effect of swietenine and its mechanisms in nonalcoholic fatty liver disease (NAFLD) in high-fat diet/streptozotocin-induced diabetic mice. The effect was assessed by determining blood biochemical parameters (glucose, cholesterol, triglycerides, alanine transaminase (ALT), asparate transaminase (AST), alkaline phosphatase (ALP), glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA)) and liver biochemical parameters (liver index, cholesterol, and triglycerides). Hepatic lipid accumulation (initial causative factor in NAFLD) was determined by oil-O-red staining. Gene expression (qPCR) and immunohistochemical studies were performed to elucidate the mechanism of swietenine's effect in NAFLD. The critical regulators (genes and proteins) involved in lipogenesis (ACLY, ACC1, FASN, SREBP1c, and ChREBPβ) and oxidative stress (Nrf2, NQO-1 and HO-1) pathways were determined. In mice fed with a high-fat diet followed by streptozotocin injection, the liver cholesterol, triglycerides, and lipids were elevated. These increases were reversed by the oral administration of swietenine, 80 mg/kg body weight, on alternate days for eight weeks. Gene expression and immunohistochemical studies showed that swietenine reversed the elevated levels of crucial enzymes of lipogenesis (ACLY, ACC1 and FASN) and their master transcription factors (SREBP1c and ChREBPβ). Furthermore, swietenine activated the Nrf2 antioxidant defense mechanism, as evidenced by the upregulated levels of Nrf2, NQO-1, and HO-1. It is concluded that swietenine shows beneficial effects in diabetes-induced NAFLD via inhibiting lipogenesis and activating the Nrf2 pathway.

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism.

BackgroundEthnopharmacological relevance: Brugmansia, a genus of the Solanaceae family, has historically been utilized in many different parts of the world as an anti-inflammatory for treating skin infections, wounds, and bodily aches and pains. The current study aimed to investigate the potential benefits of a methanolic extract of Brugmansia aurea in the management of diabetes and underlying complications in alloxanized-induced diabetic rats.Materials and methodsAnimals were divided into nine groups (n = 6). Four groups received different standard oral hypoglycemic agents; three groups received 100, 200, and 400 mg/kg of B. aurea leaf extract for six consecutive weeks, and the remaining two were normal and disease control groups. All groups received alloxan (150 mg/kg) except for the normal control. Only those animals whose glucose levels were raised to 200 mg/dl were selected for the study. After a 6-week dosage period, various biochemical parameters, as well as HbA1c, antioxidant profile, oral glucose tolerance test (OGTT), insulin sensitivity, histopathology, and insulin resistance, were measured and compared with the untreated diabetic group.ResultsBrugmansia aurea leaf extract at a dose of 400 mg/kg showed potent antidiabetic activity by reducing blood glucose levels (p < 0.001) after 6 weeks of treatment. OGTT data showed that B. aurea exhibited significant (p < 0.001) glucose tolerance by significantly reducing blood glucose levels in just 2 h post-treatment. Other tests showed that plant extract significantly increased (p < 0.001) insulin sensitivity and decreased (p < 0.001) insulin resistance. The biochemical profile showed reduced triglyceride and cholesterol, while the antioxidant profile showed restoration of antioxidant enzymes in the pancreas, kidney, and liver tissues of treated rats.ConclusionThe present study indicated that crude extracts of B. aurea increase insulin sensitivity and reduce hyperlipidemia in diabetic rats, which rationalizes the traditional medicinal use of this plant as an antidiabetic agent.

The Togolese Medicinal Recipe, Diabeto-Dolvo® Exerted Antidiabetic Effects in Wistar Rats

Objective: this study was to evaluate the toxicity of a herbal recipe Diabeto-Dolvo® (DD) and its efficacy in streptozotocin-induced diabetic Wistar rats. Methodology and results: The toxicity test was performed by oral administration of the extract to rats while diabetes was induced with streptozotocin, the 250, and 500 mg / kg body weight. The results of the toxicity tests revealed no evidence of mortality or morbidity suggesting an LD50 greater than 5000 mg / kg. Similarly, the biochemical and haematological parameters remained unchanged. In antidiabetic tests, there was a progressive decrease followed by a normalization of the glucose level of the treated rats. Overall, the extract at 250 and 500 mg / kg body weight resulted in a significant reduction in glycated haemoglobin, amylase, lipase, G6PD and serum lipids. Conclusion and application of results: This study revealed that, the treatment with the recipe might repair oxidative damages, hyperglycaemia and hyperlipidaemia in diabetic rats in the same way as the treatment with glibenclamide. This study is a contribution to the experimental validation of the DD recipe. In research and development application, the DD recipe will be used in the treatment of cases of diabetes mellitus. A natural product, it will support the multiple treatments of so-called conventional medicine, relatively expensive for the population. Key words: Diabeto-Dolvo®; blood glucose; oxidative damage; streptozotocin; diabetes mellitus; Togo.

Ameliorating effect of Malva Neglecta on hyperglycemia and hyperlipidemia in diabetic rats

Ameliorating effect of Malva Neglecta on hyperglycemia and hyperlipidemia in diabetic rats

Polysaccharide from white kidney bean can improve hyperglycemia and hyperlipidemia in diabetic rats

Type 2 diabetes (T2D), as the most common type of diabetes, has become the public problem in the world for increasing prevalence. In this study, the effects of polysaccharide from white kidney bean (WKBP) on streptozotocin-induced diabetic rats were investigated. Administration of WKBP decreased the levels of blood glucose, glycated serum protein and increased the level of insulin of diabetic rats. Treatment of WKBP reduced the concentration of total cholesterol and raised the ratio of high and low-density lipoprotein cholesterol related to serum lipids. WKBP also can lessen damage of pancreas, kidney and liver, and contribute to their function restoration. The results found that WKBP exhibited high potential on helping with hyperglycemia, hyperlipidemia and alleviating the damage of pancreas, kidney and liver of T2D.

Prunus amygdalus extract exert antidiabetic effect via inhibition of DPP-IV: in-silico and in-vivo approaches

Prunus amygdalus (PA) is a popular invasive seed utilized in the management of diabetes in Jammu and Kashmir, India. The objective of the current study was to scrutinize the antidiabetic effect of Prunus amygdalus (PA) against Streptozotocin (STZ) induced diabetic rats and explore the possible mechanism of action at cellular and sub-cellular levels. Box Benkan Design (BBD) was performed to determine the effect of PA powder to methanol, extraction time and extraction temperature on DPPH and ABTS free radical scavenging activity of decoction. In-silico study was performed on GLUT1 (5EQG) and dipeptidyl peptidase IV (DPPIV) (2G63) protein. Type II diabetes mellitus was initiated by single intra-peritoneal injection of STZ. The Blood Glucose Level (BGL) and body weight were estimated at regular interval of time. The different biochemical parameters such as hepatic, antioxidant, and lipid parameters were estimated. At end of the study, pancreas was used for histopathological observation. The variation in DPPH antiradical scavenging activity 40.0–90.0% and ABTS antiradical scavenging activity 34–82%, were estimated respectively. STZ induced DM rats showed increased BGL at end of the experimental study. PA treatment significantly (p < 0.001) down-regulated the BGL level. PA significantly (p < 0.001) altered the biochemical, hepatic and antioxidant parameters in a dose-dependent manner. Histopathological examination demonstrated the constructive mass of β-cells in pancreas. Overall, the current study indicates that the PA treatment down-regulated the hyperglycemic, oxidative stress and hyperlipidaemia in diabetic rats, due to inhibition of enzymes or amelioration of oxidative stress. Communicated by Ramaswamy H. Sarma

Evaluation of the Anti-Hypercholesterolemic and Antioxidant Activity of Mentha pulegium (L.) Aqueous Extract in Normal and Streptozotocin- Induced Diabetic Rats

Objective:Mentha pulegium L., an aromatic plant belonging to Lamiaceae family, is widely used by local population against diabetes, hypertension and cardiovascular disorders. The present study aimed to evaluate the in vivo antihypercholesterolemic effect of aerial parts aqueous extract (A.P.A.E) of Mentha pulegium (M. pulegium) in normal and streptozotocin-induced diabetic rat. Additionally, the in vitro antioxidant activity of M. pulegium A.P.A.E has been estimated.Methods:The effect of M. pulegium (L.) A.P.A.E (20 mg of lyophilized A.P.A.E per kg body weight) on plasma lipid profile was investigated in normal and streptozotocin (STZ) diabetic rats (n=6) treated for 15 days with M. pulegium (L.) A.P.A.E oral administration. The antioxidant activity was evaluated using DPPH (1-1-diphenyl 2-picryl hydrazyl) radical scavenging activity. Estimation of total polyphenol contents in A.P.A.E of M. pulegium was determined with the Folin- Ciocalteu reagent by the method using gallic acid as a standard phenolic compound. Also, flavonoids were estimated according to the method based on the formation of a complex flavonoidaluminium.Results:The results show that 15 days of M. pulegium A.P.A.E oral administration alleviated hyperlipidemia in diabetic rats by lowering significantly (p&lt;0.01) the plasma cholesterol levels without affecting the triglycerides (TG) levels significantly. However, no significant decrease in plasma cholesterol and plasma triglycerides has been shown in diabetic control rats. In addition, A.P.A.E oral administration has exerted some increasing activity on plasma HDL-c level (54.84 %), whereas the HDL-c level, in diabetic control rats, has significantly decreased (p&lt;0.05). On the other hand, M. pulegium A.P.A.E showed a high amount of flavonoid (83.07 ± 0.58 mg EQ / g of extract) and phenolic compounds (239.08 ± 35.40 mg EAG/g of extract). Also, according to the DPPH radical scavenging activity, this aqueous extract has demonstrated a significant antioxidant activity.Conclusion:We conclude that 15 days of M. pulegium A.P.A.E oral administration exhibited a significant antihypercholesterolemic effect and has also demonstrated a not negligent increase in HDL-c levels without affecting the triglycerides levels. Furthermore, A.P.A.E exhibited a potent antioxidant activity. Therefore, phytochemical compounds and antioxidant activity of M. pulegium A.P.A.E may be seemingly implicated in the antihypercholesterolemic effect demonstrated in this study.

Biological Attributes of Unfermented and Fermented Oat Milk Compared to Cow Milk in Alloxan-Induced Diabetic Rats

The present study aimed to assess the therapeutic effect of the unfermented and fermented cow; oat milk (CM, OM, FCM, and FOM) and fermented oat milk supplemented with 2% whey protein concentrate (FOM+WP) in diabetic rats. Alloxan was applied for inducing diabetes and hyperlipidemia in rats. The rats were randomly divided into two main groups. Control (-) (6 rats) were fed on a standard diet, while the second group (42 diabetics rats) were divided into six groups (6 rats each), and treated by different unfermented and fermented milk types by epigastric tube for 4 weeks. After four weeks, all treatments reduced the level of glucose, the serum levels of TC, TG and LDL-c compared to control (+) group and this was associated with a significant increase (p<0.05) in HDL-c in these groups. The highest significantly (p<0.05) decrease recorded in the groups fed with (OM) and (FCM), respectively. Liver enzymes activity decreased significantly (P˂0.05) in FOM + WP, FOM, FCM and OM groups, respectively. Feeding the rats on fermented oat milk fortified with whey protein led to decrease the fecal total anaerobes and fecal enterobacterial counts and stimulate the viability of both fecal lactobacilli and bifidobacteria in the intestinal colon, compared with other treatments. Histopathological examination of the liver sections showed no histopathological alteration in the hepatic parenchyma in (FOM+WP) group. (OM) and (FCM) groups showed no histopathological alteration and the islands of Langerhans cells were in normal size as well as the surrounding acini and ducts. In conclusion, treatment with oat milk led to curing hyperglycemia and hyperlipidemia in diabetic rats. Meanwhile, treatment with fermented oat milk fortified with whey proteins resulted in a better effect on the liver and improved the growth of the health-promoting intestinal microflora.

Protective effects of Buchholzia coriacea seeds extract and fractions on blood glucose and hyperlipidemia in diabetic rats

Background: The Buchholzia coriacea seeds (Capparaceae) are used in Nigerian ethnomedicine for treatment of hyperglycemia. Our aim, therefore, is to evaluate antihyperglycemic and hypolipidemic effects of extract and fractions of Bulcholzia coriacea seeds.Methods: The cut, dried and pulverized seeds were extracted with a mixture of methanol-dichloromethane (1:1) which yielded the crude extract, MDE. The MDE was fractionated using bioactive guided procedure and yielded hexane fraction (HF), ethylacetate fraction (EF) and methanol fraction (MF). Alloxan-induced diabetes, normoglycemic test and oral glucose tolerance test (OGTT) were the antidiabetic models employed, while hypolipidemic study was performed using standard assay kits to determine the serum total cholesterol (TC) triglycerides (TG) and low density lipoproteins (LDL). Acute toxicity test of the extract was performed using Lorke’s method while qualitative and quantitative phytochemical analyses were also performed using standard procedures.Results: The results showed an oral median lethality dose (LD50) greater than 5000mg/kg. The extract and fractions showed significant antihyperglycemic effect comparable and in synergy to metformin, a standard agent. The extract (200mg/kg) showed the highest percentage blood glucose reduction (PBGR) of 52.89% while ethylacetate fraction (EF, 400mg/kg) showed PBGR of 50.84%. Also, the MDE and hexane fraction (HF) showed a significant reduction of TC, TG and LDL and related increase in HDL-C levels in diabetic treated rats.Conclusions: The extract and the fractions of Buchholzia coriacea seeds possess antihyperglycemic and antihyperlipidemic effects and showed same mechanism of action as metformin, thus providing scientific rationale for its folkloric use.

Protective and hypoglycemic effects of celery seed on streptozotocin-induced diabetic rats: experimental and histopathological evaluation

Diabetes mellitus is a major manifestation of metabolic disorder which presents with hyperglycemia (high levels of serum blood sugar). In the present study, we aimed to investigate the effects of celery seed extract on different biochemical factors and histopathological changes in normal and streptozotocin (STZ)-induced diabetic rats. A total of 35 male Wistar rats were divided into five groups (one normal and four diabetic groups). STZ was injected intraperitoneally to induce diabetes. The effects of hexane extract of celery seed and glibenclamide (as a positive control) were compared. Blood samples were analyzed on days 0, 18, and 33, and histopathological evaluations were performed at the end of the study. Glucose, triglycerides, and cholesterol levels significantly decreased, whereas insulin and high-density lipoprotein (HDL) levels increased in the extract-administered groups, as compared to the negative diabetic control group (P<0.0001). The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of the extract-administered groups were significantly less than the negative control group (P<0.0001). Histopathological reports revealed significantly less atrophy, necrosis, and inflammation in the rats receiving celery seed extract compared to the negative control group. The results indicated that celery seed extract can be effective in controlling hyperglycemia and hyperlipidemia in diabetic rats, and demonstrated its protective effects against pancreatic toxicity resulting from STZ-induction.

Antidiabetic effect of total saponins from Polygonatum kingianum in streptozotocin-induced daibetic rats

BackgroundPolygonatum kingianum has been used in the prevention and treatment of diabetes, hyperlipidemia and related metabolic syndrome in Asian counties for centuries. In this study, the blood glucose regulation activity and mechanism of total saponins from P. kingianum (TSPK) were investigated in streptozotocin (STZ)-induced diabetic rats in this research. MethodsTSPK (0.025g/kg and 0.1mg/kg) was administrated by gavage to STZ-induced diabetic rats for 8 weeks. Changes of body weight, food intakes, blood glucose, serum insulin and lipid indexes were observed. Genome-wide expression profiling was applied to explore the gene expression alternation after treated with TSPK. Expressions of adenosine monophosphate activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK), the relative transcript level of glucose kinase and glucose-6-phosphatase (GK/G6P) in the liver were investigated. Meanwhile, contents of AMPK, and glucose transporter subtype-4 (GLUT4) in skeletal muscle, and peroxysome proliferator-activated receptor (PPAR-γ) in adipose tissue were investigated. ResultsTSPK could effectively alleviate hyperglycemia and hyperlipidemia in diabetic rats. Genome-wide expression profiling showed that TSPK up-regulated the expression of GLUT4 while down-regulated the expression of G6P in insulin signal pathway. In the liver, the expression of AMPK and GK are increased. Further more, TSPK promoted the expressions of GLUT4 in skeletal muscle, and PPAR-γ in adipose tissue, respectively. ConclusionThese results provide possible mechanisms for the antidiabetic effects of TSPK. TSPK could promote not only glycogenesis but also glucose utilization in peripheral tissue. Our results suggested that TSPK may be used as adjuvant therapy to control blood glucose and insulin resistance in type 2 diabetic individuals.

Developed beverage from roselle calyx and selected fruits modulates β-cell function, improves insulin sensitivity, and attenuates hyperlipidaemia in diabetic rats

The aim of this study is to report the antidiabetic properties of a beverage developed from roselle calyx and selected fruits in male albino rats. The beverage was designed to contain 30% pawpaw (Carica papaya L.), 10% grapefruit (Citrus paradisi), 20% guava leaves (Psidium guajava L.) and 40% roselle calyx aqueous extracts. Four groups of five rats each were acclimatized on pelletized mouse chow for seven days, after which diabetes was induced by a single ip injection of alloxan in all groups except group 1, which served as control. Group 2 served as negative control while groups 3 and 4 were treated with the beverage at 2.5 and 5 ml/kg bw respectively. Food intake, body weight, and blood glucose levels were monitored. They were sacrificed by cervical dislocation after a 2 week treatment. Blood serum was analysed to evaluate insulin levels, β cell function, insulin resistance and lipid profile. Histological studies were carried out on pancreatic tissues. Treatment with both doses of the beverage led to a significant reduction (p < 0.05) in blood glucose, total cholesterol triglyceride, LDL and increased HDL levels. It also improved serum insulin levels, β cell function, reduced insulin resistance and restored pancreatic beta cells compared to the diabetic group. These antidiabetic properties may be as a consequence of modulation of the β-cell function, reduction of insulin resistance and preservation/restoration of β-cell integrity. However, treatment with the single dose showed signs of hyperinsulinaemia.

Antidiabetic effects of Swertia macrosperma extracts in diabetic rats

Ethnopharmacological relevanceSwertia macrosperma is a traditional folk medicine used for its anti-hepatitis, antipyretic and antidotal effects as “Dida” or “Zangyinchen” in Tibet, Yunnan and Guizhou province for a long time, and it has been reported for its anti-diabetic effects in a Chinese patent. Swertia macrosperma was reported rich in xanthones, iridoids, seco-iridoids and their glycosides, several of which had been documented as potential antidiabetic agents. The objective of this study was to investigate the antidiabetic effect of Swertia macrosperma in diabetic rats. Materials and methodsThis study was designed firstly to evaluate the effect of Swertia macrosperma on glucose consumption in HepG2 cells. Based on the result in HepG2 cells, the antidiabetic effect of ethanol extract (EE) and n-butanol extract (BE) were investigated in diabetic rats induced by high fat fed and streptozotocin. The effects of EE and BE on fasting blood glucose, oral glucose tolerance test, serum insulin, glycosylated hemoglobin, serum lipid level, serum antioxidant parameters, glucokinase, glucose-6-phosphatase activities and glycogen content in liver tissue were measured, histology examination of pancreatic tissue was also carried out. ResultsAfter 4 weeks treatment with EE and BE, apparently decreased fasting blood glucose concentrations were observed in these treated groups, compared with the diabetic control groups. Additionally, improvement in serum antioxidant parameters and lipid profile were evidenced clearly. Moreover, EE and BE had effects of protecting the pancreatic β-cells and stimulating insulin secretion from the remaining pancreatic β-cells, evidenced by pancreatic histology examination. Increased glucokinase activity and decreased glucose-6-phosphatase activity were observed in liver. ConclusionThe results of in vivo and in vitro experiment suggested that EE and BE of Swertia macrosperma had excellent effects on controlling the hyperglycemia and hyperlipidemia in diabetic rats.

English

The study was designed to evaluate the effect of&nbsp;Citrullus colocynthis&nbsp;pulp hydro-ethanol extract on alloxan-induced hyperlipidemia in diabetic rats.&nbsp;24 albino rats&nbsp;with body weights of 150 to 200 g were divided into one control and three experimental groups. Group 1 was the normal control rats, orally administered physiological saline. Groups 2, 3 and 4 were diabetic rats orally administered physiological saline (diabetic, untreated), glibenclamide (diabetic, GL) or&nbsp;C. colocynthis&nbsp;extract (300 mg /kg) (diabetic, CC), respectively.&nbsp;All treatments were administered orally, on a daily basis, for a period of 30 days. At the end of the experimental period, animals in all the four groups were fasted for 12 h and then sacrificed. Blood samples and liver tissues were taken for the determination of total cholesterol, triglycerides, free fatty acids and phospholipids. Portions of the liver were homogenized and used for determination of lipid peroxidation biomarkers [thiobarbituric acid reactive substances&nbsp;(TBARS) and lipid hydroperoxides (HPx)], and for biological antioxidant levels [reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)].&nbsp; The results show significant decreases in the levels of total cholesterol, triglycerides, free fatty acids and phospholipids in serum and liver of&nbsp;C. colocynthistreated diabetic rats when compared to diabetic untreated rats.&nbsp; Also, relative to diabetic untreated rats, oral administration of&nbsp;C. colocynthis&nbsp;to diabetic rats significantly reduced elevated levels of liver TBARS and HPx to near normal levels and caused significant increases in GSH, SOD and CAT levels, an effect that is comparable to but more pronounced than that of glibenclamide. These results indicate that&nbsp;C. colocynthis&nbsp;pulp hydro-ethanol extract possesses potent hypolipidemic and antioxidant actions in alloxan induced diabetic rats.&nbsp;&nbsp; &nbsp; Key words:&nbsp;Citrullus colocynthis, alloxan diabetes, hypolipidemia, antioxidant.

Fiber-enriched biscuit enhances insulin secretion, modulates β-cell function, improves insulin sensitivity, and attenuates hyperlipidemia in diabetic rats

The nutritional properties of developed fiber-enriched biscuits and its antidiabetic potentials were investigated in alloxan-induced diabetic rats. Fiber-enriched biscuit was developed from selected fruits. Its nutritional and antinutrient properties were investigated. Diabetes was induced in rats by a single intraperitoneal injection of alloxan and the formulated biscuit was fed to the treatment group. The rats were monitored daily for food intake, and body weight. Their blood glucose levels were monitored on weekly basis. They were sacrificed by cervical dislocation after a 2-week treatment. Blood serum and hepatic tissues were analyzed to evaluate serum insulin level, insulin resistance, insulin sensitivity, β-cell function, and lipid profile. Histological study was carried out on pancreatic tissues. No significant difference was observed in diet intake among the experimental groups. However, all groups except the treated had significant (p<0.05) weight lost. Feeding on the formulated biscuits led to a significant reduction of blood glucose level, total cholesterol and LDL compared to the diabetic group. It also increased serum insulin level, improved β-cell function and reduced insulin resistance as well as restoration of pancreatic β cells. Feeding on fiber-enriched biscuit showed potent antidiabetic property as evident by the reduced blood glucose, increased serum insulin, and increased high-density-lipoprotein cholesterol levels.

Novel inhibitors of glycation and AGE formation

Accelerated formation of advanced glycation/lipoxidation and endproducts (AGEs/ALEs) has been implicated in the pathogenesis of various diabetic complications. Several natural and synthetic compounds have been proposed and tested as inhibitors of AGE/ALE formation. We have previously reported the therapeutic effects of several new AGE/ALE inhibitors on the prevention of nephropathy and dyslipidemia in streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the effects of various concentrations of a compound, LR-90, on the progression of renal disease and its effects on AGE and receptor for AGE (RAGE) protein expression on the kidneys of diabetic STZ-rats. Diabetic male Sprague-Dawley rats were treated with or without LR-90 (0, 5, 20, 25, and 50 mg/l of drinking water). After 32 weeks, body weight, glycemic status, renal function, and plasma lipids were measured. Kidney histopathology and AGE/ALE accumulation and RAGE protein expression in tissues were also determined. In vitro studies were also performed to determine the possible mechanism of action of LR-90 in inhibiting AGE formation and AGE-protein cross-linking. LR-90 protected the diabetic kidneys by inhibiting the increase in urinary albumin-to-creatinine ratio and ameliorated hyperlipidemia in diabetic rats in a concentration-dependent fashion without any effects on hyperglycemia. LR-90 treatment also reduced kidney AGE/ALE accumulation and RAGE protein expression in a concentration-dependent manner. In vitro, LR-90 exhibited general antioxidant properties by inhibiting metal-catalyzed reactions and reactive oxygen species (OH radical) and reactive carbonyl species (methlyglyoxal, glyoxal) generations without any effect on pyridoxal 5' phosphate. The compound also prevents AGE-protein cross-linking reactions. These findings demonstrate the bioefficacy of LR-90 in treating nephropathy and hyperlipidemia in diabetic animals by inhibiting AGE accumulation, RAGE protein expression, and protein oxidation in the diabetic kidney. Additionally, our study suggests that LR-90 may be useful also to delay the onset and progression of diabetic atherosclerosis as the compound can inhibit the expression of RAGE and inflammation-related pathology, as well as prevent lipid peroxidation reactions.

A new tactic to treat postprandial hyperlipidemia in diabetic rats with gastroparesis by improving gastrointestinal transit

Improvement of gastrointestinal transit was thought to be a new tactic to treat postprandial hypertriglyceridemia in diabetic individuals with gastroparesis. Diabetic gastroparesis, lipid load testing, and the effect of domperidone or aqueous extract of rhizomes of Rheum palmatum L. on postprandial hypertriglyceridemia were evaluated in alloxan-induced diabetic rats. Alloxan diabetic animals had a slow gastrointestinal transit, together with delayed and exaggerated postprandial hypertriglyceridemia, after oral administration of olive oil, which was significantly improved after oral administration of domperidone or R. palmatum L. However, atropine could prevent the effects of R. palmatum L. The reduced postprandial hypertriglyceridemia was highly correlated with the improvement in gastrointestinal transit. These results suggest that promotion of gastrointestinal transit may be useful for the treatment of postprandial hypertriglyceridemia in diabetic patients with gastroparesis. R. palmatum L. may become a new choice for these patients since it has more potential benefits than domperidone.

Attenuation of Hyperglycemia and Hyperlipidemia in Streptozotocin-Induced Diabetic Rats by Aqueous Extract of Seed of Tamarindus indica

Streptozotocin (STZ)-induced diabetic rats were divided into mild diabetic (MD) and severe diabetic (SD) on the basis of fasting blood glucose (FBG) levels. Diabetes was confirmed here by intravenous glucose tolerance test (GTT), biochemical assay of glycogen content in liver and skeletal muscle, glucose-6-phosphatase activity in liver, and serum insulin levels. Hyperlipidemia developed in these experimental diabetic rats was assessed by quantification of total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) and triglyceride (TG) in serum. Aqueous extract of seed of Tamarindus indica was given to MD and SD rats at the dose of 80 mg and 120 mg/0.5 ml distilled water/100 g body weight/d respectively for 14 d. Significant attenuation of hyperglycemia was indicated by measuring FBG, glycogen level and glucose-6-phosphatase activity along with monitoring of intravenous GTT and serum insulin level. Similarly, correction of hyperlipidemia in diabetic rats after this extract supplementation was confirmed by significant reduction in the levels of above-mentioned hyperlipidemic indicators. Intravenous GTT was performed that highlights the antidiabetic action of this extract is not due to its effect on the intestinal rate of glucose absorption but may be due to modulation of intracellular glucose utilization in target organs. This study focus the efficacy of this extract for the management of experimental diabetes in rat model which may shed some light on the scientific basis of ancient herbal therapy in this line using this seed.

Improvement in cardiac function in streptozotocin-diabetic rats by salt loading.

Effects of salt loading by drinking 0.9% NaCl solution on the myocardial performance in nondiabetic and diabetic Wistar rats were studied using the isolated working heart apparatus. Body weight and fluid and food intakes of these animals were monitored. Blood pressure and plasma levels of glucose, insulin, cholesterol, and triglycerides were also measured. Diabetes was induced by intravenous injection of streptozotocin (60 mg/kg). Diabetic rats were found to develop myocardial dysfunction at 8 weeks after STZ injection, accompanied by significant increases in food and fluid intakes, slowed body weight gain, hyperglycemia, hypoinsulinemia, and hyperlipidemia but without significant changes in blood pressure. Salt loading did not cause significant changes in any of the parameters studied in nondiabetic rats. However, in streptozotocin-diabetic rats given saline to drink, the impaired myocardial function was significantly improved and was associated with a significant reduction in hyperphagia and hyperlipidemia. Plasma glucose levels significantly decreased at weeks 1-3 but increased to the levels of untreated diabetic animals at weeks 4-7. There was an increase in fluid intake, but neither blood pressure nor plasma insulin levels were significantly affected. It is suggested that the improvements in cardiac function and hyperlipidemia in diabetic rats by salt loading may be related to each other; however, the mechanisms for these effects are not clear but are unlikely to be due to changes in glycemic control.

Role of small intestine in pathogenesis of hyperlipidemia in diabetic rats.

The small intestine can utilize endogenous substrates for triglyceride synthesis. In diabetes mellitus, potential endogenous substrates are elevated. This study was designed to investigate whether intestinal triglyceride production utilizing endogenous substrates contributes to the pathogenesis of hyperlipidemia in diabetes. Intestinal fatty acid esterification as well as activities of acyl-CoA synthetase and acyl-CoA monoglyceride acyltransferase are the same in diabetic and control rats when the results are expressed per milligram protein. However, due to marked intestinal hypertrophy these activities are increased when the results are expressed as per centimeter gut length. In the mesenteric lymph fistula rat model, we found that during fasting diabetic rats have a greater than twofold increase in triglyceride output that is carried mainly by very low-density lipoproteins (VLDL). During lipid infusion, total triglyceride fatty acid output was not different between diabetic and control rats, although there were significant differences in the patterns of partition of endogenous and exogenous triglyceride into chylomicrons and VLDL. Endogenous triglyceride production did not increase in diabetic rats during lipid infusion. In contrast, there was a substantial increase in endogenous triglyceride production in the control group to a level comparable with that of the diabetic rats. There was a significant reduction in incorporation of exogenous triglyceride into chylomicrons in diabetic rats.