Effect of 6-gingerol on AMPK- NF-κB axis in high fat diet fed rats

Objectives: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in metabolic homeostasis and regulation of inflammatory responses through attenuation of nuclear factor kappa-B (NF-kB), Thus AMPK may be a promising pharmacologic target for the treatment of various chronic inflammatory diseases. We examined the effect of 6-gingerol, an active ingredient of ginger on AMPK-NF-kB pathway in high fat diet (HFD) rats in comparison to fish oil. Methods: Protein levels of AMPK-alpha 1 and phosphorylated AMPK-a1 were measured by western blot while Sirtuin 6 (Sirt-6), resistin and P65 were estimated by RT-PCR, TNF-alpha was determined by ELISA, FFAs were estimated chemically as well as the enzymatic determination of the metabolic parameters. Results: 6-Gingerol substantially enhanced phosphorylated AMPK-a1 more than fish oil and reduced the P65 via upregulation of Sirt-6 and downregulation of resistin, and resulted in attenuation of the inflammatory molecules P65, FFAs and TNF-a more than fish oil treated groups but in an insignificant statistical manner, those effects were accompanied by a substantial hypoglycemic effect. Conclusion: Gingerol treatment effectively modulated the state of inflammatory privilege in HFD group and the metabolic disorders via targeting the AMPK-NF-kB pathway, through an increment in the SIRT-6 and substantial decrement in resistin levels. (C) 2017 Published by Elsevier Masson SAS.