Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice.

Nerium oleander L. (syn. Nerium indicum Mill. and Nerium odorum Aiton.) is used for its anti-diabetic properties in Pakistan, Algeria, Morocco and is also recognized in Ayurveda. The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). After 20 consecutive days of treatment, various diabetic parameters were studied and compared with untreated mice. Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. Different bioactive phytocompounds with potent anti-diabetic activity were identified by GC-MS and HPLC analysis. The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices.

Dey P ，Saha MR ，Chowdhuri SR ，Sen A ，Sarkar MP ，Haldar B ，Chaudhuri TK ... -  《-》

Acacia nilotica leaf improves insulin resistance and hyperglycemia associated acute hepatic injury and nephrotoxicity by improving systemic antioxidant status in diabetic mice.

Acacia nilotica (L.) Delile is used as a traditional anti-diabetic remedy in Bangladesh, Pakistan, Egypt, Nigeria and is mentioned in Ayurveda as well. The objective of the study was to evaluate the ethnomedicinal claim of A. nilotica leaf (ANL) extract for its efficiency in ameliorating diabetic complications. ANL was orally administrated (50 and 200mg/kg) to alloxanized mice (blood glucose > 200mg/dL) for 20d. Parameters of glucose metabolism, hepatotoxicity, hyperlipidemia and nephrotoxicity were measured with emphasis on elevated oxidative stress. ANL was chemically characterized using GC-MS. Further, docking studies were employed to predict molecular interactions. ANL lowered (65%, P< 0.001) systemic glucose load in diabetic mice, which was otherwise 398% higher than control. ANL lowered (35%) insulin resistance, without any significant effect on insulin sensitivity (P> 0.05). Anti-hyperglycemic properties of ANL was further supported by lowering of HbA1c (34%; P< 0.001) and improved glucose utilization (OGTT). Overall diabetic complications were mitigated as reflected by lowered hepatic (ALT, AST) and renal (creatinine, BUN) injury markers and normalization of dyslipidemia. Elevated systemic oxidative stress was lowered by increased catalase and peroxidase activities in liver, kidney and skeletal muscle, resulting in 32% decrease of serum MDA levels. Apart from high phenolic and flavonoid content, tocopherol, catechol and β-sitosterol, identified in ANL, demonstrated substantial binding affinity with Nrf2 protein (5FNQ) reflecting possible crosstalk with intracellular antioxidant defense pathways. The present study revealed the potentials of A. nilotica to alleviate diabetes-related systemic complications by limiting oxidative stress which justified the ethnopharmacological antidiabetic claim.

Saha MR ，Dey P ，Sarkar I ，De Sarker D ，Haldar B ，Chaudhuri TK ，Sen A ... -  《-》

Antidiabetic activities of chloroform fraction of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes.

Anthocleista vogelii Planch is a medicinal plant traditionally used in West Africa for the management and treatment of diabetes mellitus. To determine the antidiabetic activities of chloroform fraction (CF) of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes. Inhibitory activities of CF against α-amylase and α-glucosidase activities were determined in vitro. Three weeks old rats were fed with high-fat diet for 9 weeks to induce obesity prior to further induction of diabetes using alloxan (150 mg/kg body weight, i.p.). Blood glucose levels and body weight were measured every 7 days throughout the experiment. Glucose tolerance was assessed in normal and CF-treated rats on day 21. Terminal blood samples were collected from sacrificed animals for the measurement of serum insulin levels. Pancreases were excised from treated and untreated animals for histopathological examination. LCMS/MS chromatographic profile of CF via positive and negative modes revealed 13 and 23 compounds respectively. Further analysis revealed quebrachitol (QCT), loganin, sweroside, oleoside 11-methyl ester and ferulic acid, which have been previously reported for their antidiabetic activities, as constituents of CF. CF inhibited activities of α-amylase (IC50 = 51.60 ± 0.92 µg/ml) and α-glucosidase (IC50 = 5.86 ± 0.97 µg/ml) in a dose-dependent manner. Treatment of animals with obesity-diabetes with 100 and 200 mg/kg CF significantly improved glucose tolerance (P < 0.001) and enhanced serum insulin levels (P < 0.05) compared to diabetic control rats. Antidiabetic activities of CF might be mediated via inhibition of α-amylase and α-glucosidase activities, elevation of serum insulin concentration, and enhancement of insulin and leptin sensitivity in obesity-diabetes rats. This study further substantiates the traditional use of A. vogelii in the management and treatment of diabetes in Africa and encourages further studies to investigate its mechanism of action.

Anyanwu GO ，Iqbal J ，Khan SU ，Zaib S ，Rauf K ，Onyeneke CE ，Ojo OO ，Nisar-Ur-Rahman ... -  《-》

Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice.

Rehmannia glutinosa (Gaertn.) DC. (RG) has been widely used as traditional Chinese herbal medicine for treatment of diabetes and its complications. The polysaccharide fraction of RG has been proposed to possess hypoglycemic effect by intraperitoneal administration, however, the mechanisms responsible for the hypoglycemic effect of RG polysaccharide (RGP) remain poorly understood. Here we studied the anti-hyperglycemic and anti-hyperlipidemic effect of oral administration of a purified RGP and its underlying mechanisms in streptozotocin (STZ)-induced diabetic mice. The preliminary structure of RGP was determined by GC and FT-IR. Mice were injected with STZ to induce type 1 diabetes. RGP at doses of 20, 40 and 80 mg/kg/day was orally administered to mice for 4 weeks, and metformin was used as positive control. After 4 weeks, the blood biochemical parameters, the pancreatic insulin contents, in vitro insulin secretion, the hepatic glycogen contents and mRNA expression of phosphoenolpyruvate carboxyl kinase (PEPCK) were assayed. RGP was composed of rhamnose, arabinose, mannose, glucose and galactose in the molar ratio of 1.00:1.26:0.73:16.45:30.40 with the average molecular weight of 63.5 kDa. RGP administration significantly decreased the blood levels of glucose, total cholesterol, triglycerides, low density lipoprotein-cholesterol, and increased the blood levels of high density lipoprotein-cholesterol and insulin in diabetic mice, concurrent with increases in body weights and pancreatic insulin contents. The in vitro study revealed that RGP significantly enhanced both basal and glucose-stimulated insulin secretions, as well as islet insulin contents in the pancreatic islets of diabetic mice. Moreover, RGP reversed the increased mRNA expression of PEPCK and the reduced glycogen contents in the liver of diabetic mice. Furthermore, RGP exhibited potent anti-inflammatory and anti-oxidative activities, as evidenced by the decreased blood levels of TNF-α, IL-6, monocyte chemoattractant protein-1, MDA, and also the elevated blood levels of SOD and GPx activities in diabetic mice. Taken together, RGP can effectively ameliorate hyperglycemia, hyperlipemia, vascular inflammation and oxidative stress in STZ-induced diabetic mice, and thus may be a potential therapeutic option for type 1 diabetes.

Zhou J ，Xu G ，Yan J ，Li K ，Bai Z ，Cheng W ，Huang K ... -  《-》

Antidiabetic and antioxidant potential of Emblica officinalis Gaertn. leaves extract in streptozotocin-induced type-2 diabetes mellitus (T2DM) rats.

Nain P ，Saini V ，Sharma S ，Nain J ... -  《-》