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

• Published in: Biomedicine & pharmacotherapy 2017-04, Vol.88, p.293-301
• Main Authors: Hashem, Reem M, Rashed, Laila A, Hassanin, Kamel M.A, Hetta, Mona H, Ahmed, Asmaa O
• Format: Article
• Language: English
• Subjects: 6-Gingerol; Adipose Tissue - pathology; AMP-Activated Protein Kinases - drug effects; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Body Weight - drug effects; Catechols - pharmacology; Diet, High-Fat - adverse effects; Fatty Alcohols - pharmacology; Fish Oils; High fat diet; Internal Medicine; Male; Medical Education; NF-kappa B - drug effects; NF-kappa B - metabolism; p65; Phosphorylation; Rats; Rats, Wistar; Resistin; Signal Transduction - drug effects; Sirtuin 6; Sirtuins - drug effects; Sirtuins - metabolism; Transcription Factor RelA - drug effects; Transcription Factor RelA - metabolism; Tumor Necrosis Factor-alpha - metabolism; Zingiber officinale - chemistry
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.01.035

Abstract 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-κB), 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-κB pathway in high fat diet (HFD) rats in comparison to fish oil. Methods Protein levels of AMPK-α1 and phosphorylated AMPK-α1 were measured by western blot while Sirtuin 6 (Sirt-6), resistin and P65 were estimated by RT-PCR, TNF-α 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-α1 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-α 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-κB pathway, through an increment in the SIRT-6 and substantial decrement in resistin levels.