Document Detail

Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation.
MedLine Citation:
PMID:  18355329     Owner:  NLM     Status:  MEDLINE    
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.
R R Ortiz-Andrade; J C Sánchez-Salgado; G Navarrete-Vázquez; S P Webster; M Binnie; S García-Jiménez; I León-Rivera; P Cigarroa-Vázquez; R Villalobos-Molina; S Estrada-Soto
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-18
Journal Detail:
Title:  Diabetes, obesity & metabolism     Volume:  10     ISSN:  1463-1326     ISO Abbreviation:  Diabetes Obes Metab     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-12-02     Completed Date:  2009-08-20     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  100883645     Medline TA:  Diabetes Obes Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  1097-104     Citation Subset:  IM    
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico.
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MeSH Terms
Blood Glucose / analysis,  metabolism
Diabetes Mellitus, Experimental / drug therapy*,  metabolism
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism
Flavanones / therapeutic use*,  toxicity
Glucose Tolerance Test
Glyburide / therapeutic use
Hypoglycemic Agents / therapeutic use*,  toxicity
Lethal Dose 50
Random Allocation
Rats, Wistar
Triglycerides / blood
Reg. No./Substance:
0/Blood Glucose; 0/Flavanones; 0/Hypoglycemic Agents; 0/Triglycerides; 10238-21-8/Glyburide; 480-41-1/naringenin

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