Subramani Srinivasan

Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats.

The purpose of this study was to investigate the effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Diosmin was administered to streptozotocin-induced (45 mg/kg b.w) diabetic rats at different doses (25, 50, 100 mg/kg b.w) for 45 days to assess its effect on fasting plasma glucose, insulin, glycosylated hemoglobin, hemoglobin and carbohydrate metabolic enzymes, it was found that plasma glucose was significantly reduced in a dose-dependent manner when compared to the diabetic control. In addition, oral administration of diosmin (100mg/kg b.w) significantly decreased glycosylated hemoglobin and increased hemoglobin and plasma insulin. The activities of the hepatic key enzymes such as hexokinase and glucose-6-phosphate dehydrogenase were significantly increased whereas, glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly decreased. Furthermore, protection against body weight loss of diabetic animals was also observed. These results showed that diosmin has potential antihyperglycemic activity in streptozotocin-nicotinamide-induced diabetic rats.

Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats

Oxidative stress has been suggested as a contributory factor in development and complication of diabetes. The aim of the study was to evaluate the effect of diosmin (DS) in oxidative stress in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats by measuring the lipid peroxidation (LPO) as well as the ameliorative properties. Experimental diabetes was induced by a single intraperitoneal (i.p) injection of STZ (45 mg/kg body weight (b.w.)) dissolved in 0.1 mol/L citrate buffer (pH 4.5), 15 min after the i.p administration of NA (110 mg/kg b.w.). Diabetic rats exhibited increased plasma glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of low-molecular weight antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with DS (100mg/kg/day) for a period of 45 days showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that DS has potential ameliorative effects in addition to its antidiabetic effect in type 2 diabetic rats.

Syringic acid, a novel natural phenolic acid, normalizes hyperglycemia with special reference to glycoprotein components in experimental diabetic rats

Abstract Objective To evaluate the antidiabetic effect of syringic acid, a natural phenolic compound on the levels of glycoprotein components in plasma and tissues of alloxan induced diabetic rats. Methods Diabetes was induced in male Wistar rats by a single intraperitoneal injection of alloxan (150 mg/kg b.w). Syringic acid (50 mg/kg b.w) was administered orally for 30 d. The effects of syringic acid on plasma glucose, insulin, C-peptide, plasma and tissue glycoproteins were studied. Results Oral administration of syringic acid (50 mg/kg b.w) for 30 d positively modulates the glycemic status in alloxan induced diabetic rats. The levels of plasma glucose were decreased with significant increase of plasma insulin and C-peptide level. The altered levels of plasma and tissue glycoprotein components were restored to near normal. No significant changes were noticed in normal rats treated with syringic acid. Conclusions The present findings suggest that syringic acid can potentially ameliorate glycoprotein components abnormalities in addition to its antidiabetic effect in experimental diabetes, further clinical studies are required to evaluate the use of syringic acid as an effective therapeutic agent for the treatment of diabetes mellitus.

Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats.

Epidemiological studies have demonstrated that the diabetes mellitus is a serious health burden for both governments and healthcare providers. The present study was hypothesized to evaluate the antihyperglycemic potential of fraxetin by determining the activities of key enzymes of carbohydrate metabolism in streptozotocin (STZ) - induced diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg b.w). Fraxetin was administered to diabetic rats intra gastrically at 20, 40, 80 mg/kg b.w for 30 days. The dose 80 mg/kg b.w, significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as glucokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and hepatic enzymes (aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP)) in the liver tissues of diabetic rats were significantly reverted to near normal levels by the administration of fraxetin. Further, fraxetin administration to diabetic rats improved body weight and hepatic glycogen content demonstrated its antihyperglycemic potential. The present findings suggest that fraxetin may be useful in the treatment of diabetes even though clinical studies to evaluate this possibility may be warranted.

Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Abstract Context: Geraniol, an acyclic monoterpene alcohol is found in medicinal plants, is used traditionally for several medical purposes including diabetes. Objectives: The present study evaluates the antihyperglycemic potential of geraniol on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Diabetes was induced in experimental rats, by a single intraperitoneal (i.p) injection of STZ [40 mg/kg body weight (b.w.)]. Different doses of geraniol (100, 200 and 400 mg/kg b.w.) and glyclazide (5 mg/kg b.w.) were administrated orally to diabetic rats for 45 days. Body weight, food intake, plasma glucose, insulin, blood haemoglobin (Hb), glycosylated haemoglobin (HbA1c), hepatic glucose metabolic enzymes and glycogen were examined. Results: The LD50 value of geraniol is 3600 mg/kg b.w. at oral administration in rats. Administration of geraniol in a dose-dependent manner (100, 200, 400 mg/kg b.w.) and glyclazide (5 mg/kg b.w.) for 45 days significantly improved the levels of insulin, Hb and decreased plasma glucose, HbA1C in diabetic-treated rats. Geraniol at its effective dose (200 mg/kg b.w.) ameliorated the altered activities of carbohydrate metabolic enzymes near normal effects compared with two other doses (100 and 400 mg/kg b.w.). Geraniol treatment to diabetic rats improved hepatic glycogen content suggesting its anti-hyperglycemic potential. Geraniol supplement was found to preserve the normal histological appearance of hepatic cells and pancreatic β-cells in diabetic rats. Discussion and conclusions: The present findings suggest that geraniol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes even though clinical studies used to evaluate this possibility are warranted.

Antidiabetic efficacy of citronellol, a citrus monoterpene by ameliorating the hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats.

Diabetes mellitus is a clinically complex disease characterized by chronic hyperglycemia with metabolic disturbances. During diabetes, endogenous hepatic glucose production is increased as a result of impaired activities of the key enzymes of carbohydrate metabolism. The purpose of the present study was to evaluate the antidiabetic efficacy of citronellol, a citrus monoterpene in streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40 mg/kg b.w). STZ induced diabetic rats received citronellol orally at the doses of 25, 50, and 100 mg/kg b.w for 30 days. In this study the levels of plasma glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA1C), glycogen, and the activities of carbohydrate metabolic enzymes, liver and kidney markers were evaluated. Oral administration of citronellol (50 mg/kg) for 30 days dose dependently improved the levels of insulin, Hb and hepatic glycogen with significant decrease in glucose and HbA1C levels. The altered activities of carbohydrate metabolic enzymes, hepatic and kidney markers were restored to near normal. Citronellol supplement was found to be effective in preserving the normal histological appearance of hepatic cells and insulin-positive β-cells in STZ-rats. Our results suggest that administration of citronellol attenuates the hyperglycemia in the STZ-induced diabetic rats by ameliorating the key carbohydrate metabolic enzymes and could be developed as a functional and nutraceutical ingredient in combating diabetes mellitus.

Beneficial effect of carvone, a dietary monoterpene ameliorates hyperglycemia by regulating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats

Diabetes mellitus is a common metabolic/endocrine disorder characterized by inadequate control of carbohydrate metabolism and causes serious health issues. This study evaluates the effect of carvone, a novel monoterpene ketone, on carbohydrate metabolic enzymes in the liver of normal and streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (40mg/kg b.w). STZ intoxication led to a significant increase in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and decrease in the levels of insulin and hemoglobin (Hb). The activities of carbohydrate metabolic enzymes, glycogen, enzymatic antioxidants in pancreas and hepatic markers content were also altered. The daily oral administration of carvone (50mg/kg b.w) to diabetic rats for 30days resulted a significant decline in the levels of plasma glucose, HbA1c and significant improve in the levels of Hb and insulin. The reversed activities of carbohydrate metabolic enzymes, enzymic antioxidants and hepatic marker enzymes in diabetic rats were renovated to near normal level by the administration of carvone. The obtained results were compared with glyclazide, a standard oral hypoglycemia drug. Histopathological analysis of liver and pancreas and immunohistochemistry of pancreas revealed that treatment with carvone reduced the STZ-induced damage to hepatic and β-cells of the pancreas. From our results, carvone regulates carbohydrate metabolism by ameliorating the key enzymes in the hepatic tissues of STZ-induced diabetic rats however further studies and safety studies are needed to validate the effects of carvone.

Antihyperglycemic effect of carvone: Effect on the levels of glycoprotein components in streptozotocin-induced diabetic rats

Abstract Objective To investigate the effect of carvone on dearrangement in glycoprotein levels in the streptozotocin(STZ)-induced diabetic model. Methods Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w). The levels of glycoproteins were altered in experimental diabetes mellitus. Carvone were administered to diabetic rats intragastrically at 25, 50, 100 mg/kg bw for 30 d. The effects of carvone on plasma glucose, insulin, plasma and tissue glycoproteins were studied. Results Oral administration of carvone (50 mg/kg b.w) for 30 d, dose dependently improved the glycemic status in STZ-induced diabetic rats. The levels of plasma glucose were decreased with significant increase of plasma insulin level. The altered levels of plasma and tissue glycoprotein components were restored to near normal. Conclusions The present findings suggest that carvone can potentially ameliorate glycoprotein components abnormalities in addition to its antihyperglycemic effect in experimental diabetes. In light of these advantageous results, it is advisable to broaden the scale of use of carvone in a trial to alleviate the adverse effects of diabetes.

Antidiabetogenic efficiency of menthol, improves glucose homeostasis and attenuates pancreatic β-cell apoptosis in streptozotocin–nicotinamide induced experimental rats through ameliorating glucose metabolic enzymes

The phytochemical, menthol, has been reported to play many beneficial roles. However, under diabetic conditions, there is no detail mechanism of its beneficial action in the glucose homeostasis. The present study, we investigated to explore the role of menthol, on the glucose metabolic enzymes and pancreatic islet cell apoptosis of streptozotocin-nicotinamide (STZ-NA) induced diabetes in rats. Diabetes was induced by single intraperitoneal (i.p.) injection of STZ (50mg/kg/b.w.) and NA (110mg/kg/b.w.). Diabetic rats were treated with different dose of menthol (25, 50, and 100mg/kg/b.w.) and glibenclamide (600μg/kg/b.w.) daily for 45 days. The result of our study shows that menthol significantly reduced the blood glucose and glycosylated hemoglobin levels and significantly increased the total hemoglobin, plasma insulin and liver glycogen levels in diabetic rats. The altered activities of hepatic glucose metabolic enzymes, serum biomarkers of liver damage were restored to near normal. The pathological abnormalities in hepatic and pancreatic islets of diabetic rats were significantly ameliorated by menthol intervention. These effects were mediated by suppressing pancreatic β-cells apoptosis and were associated with increased anti-apoptotic Bcl-2 expression and reduced pro-apoptotic Bax expression. Findings from the current study consent us to conclude that menthol alleviates STZ-NA-induced hyperglycemia via modulating glucose metabolizing enzymes, suppression of pancreatic β-cells apoptosis and altered hepatic, pancreatic morphology. This exclusivity and dearth of any noticeable adverse efficacy proposes the opportunity of using this monoterpene as an efficient adjuvant in the management diabetes mellitus.

Allyl methyl sulfide, an organosulfur compound alleviates hyperglycemia mediated hepatic oxidative stress and inflammation in streptozotocin - induced experimental rats

Therapeutic approaches based on dietary compounds obtained from food products to handle diabetes involving oxidative stress and inflammation. Garlic is a common spice and has a long history as a folk remedy. Allyl methyl sulfide (AMS) is a potential garlic-derived organosulfur compound displaying a substantial range of optimistic actions in various diseases. Herein, we investigated the potential role of AMS in ameliorating the effects of oxidative stress and inflammation in the liver of streptozotocin (STZ)-induced experimental rats. Diabetes was induced by single intraperitoneal (i.p.) injection of STZ (40 mg/kg/b.w). STZ-induced hyperglycemic rats received daily intragastric doses of 50, 100 and 200 mg/kg/b.w of the AMS for 30 days. Dietary intervention of AMS (100 mg/kg b.w) resulted in significant attenuation in blood glucose and expression of pro-inflammatory markers TNF-α, IL-6, NF-κB p65 unit and significant elevation in the plasma insulin level. Moreover, AMS instigated a marked enhance in the levels of hepatic tissue non enzymatic antioxidants and the activities enzymatic antioxidants of diabetic rats with significant decline in lipid peroxides and hydroperoxides formation, serum biomarkers of liver damage, thus representing the protecting efficacy of AMS in hyperglycemic state. The pathological abnormalities in hepatic tissues of diabetic rats were significantly ameliorated by AMS supplementation and offered great support to the biochemical findings. These conclusions explicate the prospective use of AMS as a promising compound against glucotoxicity mediated hepatic oxidative dysfunction in rats. Clinical trials in validating this benefit for optimizing the AMS nutrition are however warranted.