Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation.

AIM: The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. METHODS: Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 microM) on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. RESULTS: Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin-nicotinamide-induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of alpha-glucosidase activity in vitro. However, NG (10 microM) was shown to inhibit 11beta-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD(50) > 5000 mg/kg and ranking at level five based on OECD protocols. CONCLUSION: Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels.

alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent.

Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.

Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum vitifolium (Willd.) Sprengel: a potential agent for the treatment of metabolic syndrome.

Cochlospermum vitifolium (Willd.) Sprengel is a Mexican medicinal plant that is used in the folk medicine for the treatment of hypertension, diabetes, hepatitis and related diseases. The purpose of the present study was to assess the pharmacological properties of different extracts from Cochlospermum vitifolium bark as potential agent for the treatment of some factors related with metabolic syndrome (MS), a complex disease produced for several pathophysiological factors such as visceral fat obesity, insulin resistance, hypertension, dyslipidemia and liver steatosis. Hexane (HECv), dichloromethane (DECv) and methanol (MECv) extracts were subjected to some pharmacological assays to determine their vasorelaxant and hypoglycemic activity. On the other hand, MECv was also evaluated to determine its hepatoprotective effect on sub-chronic experimental assay. HECv showed a significant endothelium-independent relaxation on rat aorta rings (intact endothelium: IC(50)=14.42+/-5.90 microg/mL, E(max)=92.71+/-8.9%; denuded endothelium: IC(50)=27.94+/-4.0 microg/mL, E(max)=78.68+/-4.6%) and MECv produced an endothelium-dependent relaxation (IC(50)=21.94+/-6.87 microg/mL, E(max)=79.12+/-7.80%) on this tissue. Furthermore, HECv (at a dose of 120 mg/kg) also showed a significant decrease of blood glucose levels (p<0.05) on normoglycemic rats. Moreover, MECv (at a dose of 100 mg/kg) also was administered to bile duct-obstructed rats to determine its hepatoprotective activity, showing a statistically significant decrease of serum glutamic-pyruvic transaminase (PGT, 45%) and alkaline phosphatase (APh, 15%) (p<0.05). Finally, we obtained a crystalline polyphenolic compound from MECv by spontaneous precipitation. Those crystals were identified as (+/-)-naringenin by X-ray diffraction, NMR, IR and GC-MS techniques. Results suggest that Cochlospermum vitifolium could be used as a potential agent against MS since it shows hypoglycemic, vasorelaxant and hepatoprotective properties.

Anti-diabetic effect on alloxanized and normoglycemic rats and some pharmacological evaluations of Tournefortia hartwegiana.

The purpose of the present investigation was to assess the pharmacological properties of Tournefortia hartwegiana Steud (Boraginaceae), used in traditional medicine for the treatment of diabetes, diarrhea and kidney pain in Morelos, Mexico. Administration of methanol extract from aerial parts of Tournefortia hartwegiana (310 mg/kg body weight/day) for 10 days, to normoglycemic and alloxan-induced diabetic rats, significantly lowered their blood glucose levels (37 and 36%, respectively, p<0.05). The anti-diabetic and hypoglycemic activities due to the MeOH extract were similar to those produced by metformin at 120 mg/kg (positive control, p<0.05). In contrast, the hexane, dichloromethane and MeOH extracts from the same species showed no significant spasmolytic effect and did not have activity in antibacterial and Artemia salina toxicity bioassays.