Antidiabetic and antihyperlipidemic activity of asiatic acid in diabetic rats, role of HMG CoA: in vivo and in silico approaches.

Hyperlipidemia is an associated complication of diabetes and also a major risk factor for cardiovascular diseases. The present study was designed to examine the antihyperlipidemic effect of asiatic acid (AA) in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.). Diabetic rats show increased plasma glucose, total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density liprotein, atherogenic index and decreased insulin and high density lipoprotein in diabetic rats. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly in contrast to the activities of lipoprotein lipase and lecithin cholesterol acyltransferase. In addition, the molecular docking of AA against HMG CoA reductase involved in cholesterol biosynthesis using Argus software. Diabetic rats were treated with AA shifted all these parameters towards normalcy. AA has shown best ligand binding energy 11.8122 kcal/mol. The antihyperlipidemic effect of AA was compared with glibenclamide; a well-known antihyperglycemic drug. In conclusion, this study indicates that AA showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes.

Modulatory effect of sesamol on DOCA-salt-induced oxidative stress in uninephrectomized hypertensive rats.

The present study was undertaken to investigate the antihypertensive and antioxidant effects of sesamol on uninephrectomized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Hypertension was induced in surgically single-kidney-removed (left) adult male albino Wistar rats, weighing 180-200 g, by injecting DOCA (25 mg/kg BW) subcutaneously twice a week for 6 weeks, with saline instead of tap water for drinking. Rats were treated with three different doses of sesamol (50, 100 and 200 mg/kg BW) post-orally by gavage daily for 6 weeks. Hypertension was revealed by increased systolic and diastolic blood pressure and the toxicity of DOCA-salt was determined using hepatic marker enzymes, aspartate aminotransferase, alanine aminotransferase, alkaline phospatase and gamma-glutamyl transpeptidase; and, lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes were assayed. The activities of enzymatic antioxidants, superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were evaluated in erythrocytes, plasma and tissues. Post-oral administration of sesamol at the dosage of 50 mg/kg BW remarkably decreased systolic and diastolic blood pressure, hepatic marker enzyme activities and lipid peroxidation products and also enhanced the antioxidant activity. The biochemical observations were also supported by histopathological examinations of the rat liver, kidney and heart sections. These results suggest that sesamol possesses antihypertensive and antioxidant effects.

Protective effects of D-limonene on lipid peroxidation and antioxidant enzymes in streptozotocin-induced diabetic rats.

The aim of this study was to evaluate the protective effects of D-limonene on the levels of lipid peroxidation by-products and antioxidant defence systems in the plasma and tissues of normal and streptozotocin (STZ)-induced diabetes rats. The experimental diabetes was induced in rats by a single dose of STZ (40 mg/kg i.p.) injection, and treatment with D-limonene was continued for 45 days. After the treatment period, oxidative stress parameters such as lipid peroxidation by-products; enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase; non-enzymic antioxidants including reduced glutathione, Vitamins C and E were measured in the plasma and tissues of experimental rats. An increase in the levels of lipid peroxidation by-products and significant decrease in antioxidant enzymes were observed in untreated diabetic rats. Administration of D-limonene to diabetic rats for 45 days caused a significant reduction in the levels of lipid peroxidation by-products and an increase in the activities of antioxidant enzymes, when compared with the untreated diabetic group. There was no significant difference in normal treated groups, when compared with normal rats. Biochemical observations were substantiated with the help of histopathological examinations through its antioxidant properties and thereby conferred protection against STZ-induced diabetic rats. The result of this study indicates that D-limonene has antioxidant potential in addition to its antidiabetic effect in experimental diabetes.

Efficacy of asiatic acid, a pentacyclic triterpene on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats.

Asiatic acid (AA), a triterpenoid derivative of Centella asiatica, has shown significant biological effects of antioxidant and anti-inflammatory activities. Aim of this investigation was to evaluate the antihyperglycemic effect of AA on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. To induce diabetes mellitus, rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg/kg b.w. Diabetic rats showed significant (p<0.05) increased in plasma glucose, glycosylated hemoglobin and significant (p<0.05) decreased in circulating insulin and hemoglobin. The altered activities of key enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase of carbohydrate metabolism significantly (p<0.05) increased whereas hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and glycogen content significantly (p<0.05) decreased in the liver of diabetic rats and also increased activities of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Oral administration of AA (5, 10 and 20 mg/kg b.w.) and glibenclamide (600 µg/kg b.w.) to diabetic rats for 45 days prevented the above alteration and reverted to near normalcy. Protection of body weight loss of diabetic rats by AA was also observed. No significant effect was observed in normal rats treated with AA (20 mg/kg b.w.). In this search, AA found to be potential bioactive compound to regulate the carbohydrate metabolism by modulating the key regulatory enzymes in diabetic rats. These findings merit further research in this field.

Effect of Rebaudioside A, a diterpenoid on glucose homeostasis in STZ-induced diabetic rats

Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently proposed as an insulinotropic agent. The aim of this investigation was to evaluate the antihyperglycemic effect of Reb A on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a single intraperitoneal injection at a dose of STZ (40 mg/kg body weight). Diabetic rats showed significant (P < 0.05) increase in the levels of plasma glucose and glycosylated hemoglobin and significant (P < 0.05) decrease in the levels of plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly (P < 0.05) increased while hexokinase and glucose-6-phosphate dehydrogenase were significantly (P < 0.05) decreased in the liver along with glycogen. Oral treatment with Reb A to diabetic rats significantly (P < 0.05) decreased blood glucose and reversed these hepatic carbohydrate metabolizing enzymes in a significant manner. Histopathology changes of pancreas confirmed the protective effects of Reb A in diabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic activity and provide evidence for its traditional usage in the control of diabetes (AU)

Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal formulation in alloxan induced hyperglycemic rats.

BACKGROUND: This study was undertaken to investigation the effect of Diasulin, a poly herbal drug composed of ethanolic extract of ten medicinal plants on blood glucose, plasma insulin, tissue lipid profile, and lipidperoxidation in alloxan induced diabetes. METHODS: Ethanolic extract of Diasulin a, poly herbal drug was administered orally (200 mg/kg body weight) for 30 days. The different doses of Diasulin on blood glucose and plasma insulin in diabetic rats were studied and the levels of lipid peroxides [TBARS, and hydroperoxide] and tissue lipids [cholesterol, triglyceride, phospholipides and free fatty acids] were also estimated in alloxan induced diabetic rats. The effects were compared with glibenclamide. RESULT: Treatment with Diasulin and glibenclamide resulted in a significant reduction of blood glucose and increase in plasma insulin. Diasulin also resulted in a significant decrease in tissue lipids and lipid peroxide formation. The effect produced by Diasulin was comparable with that of glibenclamide. CONCLUSION: The decreased lipid peroxides and tissue lipids clearly showed the antihyperlipidemic and antiperoxidative effect of Diasulin apart from its antidiabetic effect.