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Evidence-Based Complementary and Alternative Medicine
Volume 2011 (2011), Article ID 538671, 9 pages
Research Article

The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content

1Department of Pharmacology and Montreal Diabetes Research Center, Université de Montréal, Montréal, QC, Canada H3C 3J7
2Institut des Nutraceutiques et des Aliments Fonctionnels, Laval University, Quebec City, QC, Canada G1K 7P4
3Research Team in Pharmacokinetics, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat-Souissi, Morocco

Received 5 July 2010; Revised 26 January 2011; Accepted 15 February 2011

Copyright © 2011 Ali Benhaddou-Andaloussi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The antidiabetic effect of N. sativa seed ethanol extract (NSE) was assessed in Meriones shawi after development of diabetes. Meriones shawi were divided randomly into four groups: normal control, diabetic control, diabetic treated with NSE (2 g eq plant/kg) or with metformin (300 mg/kg) positive control, both administered by daily intragastric gavage for 4 weeks. Glycaemia and body weight were evaluated weekly. At study's end, an Oral Glucose Tolerance Test (OGTT) was performed to estimate insulin sensitivity. Upon sacrifice, plasma lipid profile, insulin, leptin, and adiponectin levels were assessed. ACC phosphorylation and Glut4 protein content were determined in liver and skeletal muscle. NSE animals showed a progressive normalization of glycaemia, albeit slower than that of metformin controls. Moreover, NSE increased insulinemia and HDL-cholesterol, compared to diabetic controls. Leptin and adiponectin were unchanged. NSE treatment decreased OGTT and tended to decrease liver and muscle triglyceride content. NSE stimulated muscle and liver ACC phosphorylation and increased muscle Glut4. These results confirm NSE's previously reported hypoglycaemic and hypolipidemic activity. More significantly, our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulin-independent AMPK signaling pathway, and by enhancing muscle Glut4 expression.