Multiple molecular targets underlie the antidiabetic effect of Nigella sativa seed extract in skeletal muscle, adipocyte and liver cells.
OBJECTIVE
Nigella sativa (N. sativa) is a plant widely used in traditional medicine of North African countries. During the last decade, several studies have shown that extracts from the seeds of N. sativa have antidiabetic effects.


METHODS
Our group has recently demonstrated that N. sativa seed ethanol extract (NSE) induces an important insulin-like stimulation of glucose uptake in C2C12 skeletal muscle cells and 3T3-L1 adipocytes following an 18 h treatment. The purpose of the present study was to elucidate the pathways mediating this insulin-like effect and the mechanisms through which these pathways are activated.


RESULTS
Results from western immunoblot experiments indicate that in C2C12 cells as well as in H4IIE hepatocytes, but not in 3T3-L1 cells, NSE increases activity of Akt, a key mediator of the effects of insulin, and activity of AMP-activated protein kinase (AMPK), a master metabolic regulating enzyme. To test whether the activation of AMPK resulted from a disruption of mitochondrial function, the effects of NSE on oxygen consumption were assessed in isolated liver mitochondria. NSE was found to exhibit potent uncoupling activity.


CONCLUSIONS
Finally, to provide an explanation for the effects of NSE in adipocytes, PPARgamma stimulating activity was tested using a reporter gene assay. Results indicate that NSE behaves as an agonist of PPARgamma. The data supports the ethnobotanical use of N. sativa seed oil as a treatment for diabetes, and suggests potential uses of this product, or compounds derived thereof, against obesity and the metabolic syndrome.
Benhaddou-Andaloussi
A
A
Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Montreal Diabetes Research Centre, Université de Montréal, Montreal, Quebec, Canada H3C 3J7.
Martineau
L C
LC
Vallerand
D
D
Haddad
Y
Y
Afshar
A
A
Settaf
A
A
Haddad
P S
PS
D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D031881:Nigella sativa / Q000737:chemistry*; D047495:PPAR gamma / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases