Benhaddou-Andaloussi A, Martineau LC, Spoor D, Leduc
C, Meddah B, Settaf A, Baddouri K, Haddad PS.
The antidiabetic action of Nigella sativa is mediated
by insulin-sensitizing activity in muscle cells and adipocytes.
University of Montreal, R-401 Pavillon Roger Gaudry,
2900 douard Monpetit, Montreal, Quebec H3T 1J4, Canada. b_andaloussi@yahoo.fr
Nigella sativa seeds, commonly known as black seed
or black cumin, are used in North African and Middle Eastern traditional
medicine as treatment for diabetes. Despite a widespread use, cellular
mechanisms of action are not well understood. The purpose of the project
was to confirm the anti-diabetic action of N. sativa in cell-based bioassays
and elucidate mechanisms of action. Crude ethanolic extract (200 µg/ml)
was applied 20 h to differentiated C2C12 muscle cells and 3T3-L1 adipocytes,
two insulin-sensitive cell lines, and effects on insulin-dependent and
-independent glucose uptake were assessed by H-deoxyglucose transport
assays in the presence or absence of insulin. In muscle cells, N. sativa
increased basal glucose uptake by over 50% and insulin-stimulated glucose
uptake by 30-50%. This effect was consistently greater than that of
400 mM metformin. In fat cells, basal uptake was increased by over 60%,
while stimulated uptake was increased up to 50%. Extract was also applied
to differentiating 3T3-L1 pre-adipocytes over a 6 day period to test
for acceleration of adipogenesis, a hallmark of the thiazolidinedione
class of anti-diabetic drugs. N. sativa increased triglyceride content
by three-fold, an effect comparable to 10 µM of rosiglitazone.
Western immunoblot analysis of insulin signal transduction pathways
revealed that N. sativa increases activity of Akt and ERK MAPK in an
insulin-independent manner in both muscle and fat cells. It is concluded
that N. sativa mimics and enhances the action of insulin in muscle and
fat cells. Furthermore, the effect of N. sativa on adipogenesis suggests
that it can affect the expression of genes regulating insulin sensitivity
by way of PPAR nuclear receptors. These data are consistent with our
recent in-vivo study of the insulin-sensitizing effects of Nigella sativa
(Le et al., J. Ethnopharmacology, 2004) and support the ethnopharmacological
use of this plant for the management of diabetes. This work was supported
by the Canadian Diabetes Association.
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