Pharmaceutical Chemistry and Drug Design

Nigella sativa (NS) is black seed with different biological activities and its anti-diabetic effect is one of the highly investigated activities. Streptozotocin-induced diabetic rats (fed with a high-fat diet) were treated daily with NS Oil (NSO) in order to study its anti-liver or brain insulin resistance. In the hepatic tissues, the administration of NSO significantly induced the gene expression of insulin receptor compared to NSO-untreated rats. In addition, it up-regulated the expression of insulin-like growth factor 1 and phosphoinositide-3 kinase. On the other hand, the expression of ADAM-17 was down-regulated, whereas the level of TIMP-3 confirmed its down-regulation. In the brain, it corrected the reduced insulin signaling pathway (p-IRS/ p-AKT/p-GSK-3β) resulted from the stimulation of GSK-3β level. This, in turn, contributed to a decreased Tau phosphorylation along with changes in the protein phosphatase PP2A level. In conclusion, NSO or its combined treatments with anti-diabetic drugs have a possible protective and modifying effect of the insulin resistance through enhancing the hepatic and brain insulin signaling pathway.