Hashem Reem M, Rashed Laila A, Hassanin Kamel M A, Hetta Mona H, Ahmed Asmaa O
Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt.
Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
Biomed Pharmacother. 2017 Apr;88:293-301. doi: 10.1016/j.biopha.2017.01.035. Epub 2017 Jan 21.
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.
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.
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.
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.
单磷酸腺苷(AMP)激活的蛋白激酶(AMPK)在代谢稳态及通过减弱核因子κB(NF-κB)调节炎症反应中起核心作用,因此AMPK可能是治疗各种慢性炎症性疾病的一个有前景的药理学靶点。我们比较了姜的活性成分6-姜酚与鱼油对高脂饮食(HFD)大鼠AMPK-NF-κB通路的影响。
通过蛋白质免疫印迹法检测AMPK-α1和磷酸化AMPK-α1的蛋白水平,通过逆转录聚合酶链反应(RT-PCR)评估沉默调节蛋白6(Sirt-6)、抵抗素和P65,通过酶联免疫吸附测定法(ELISA)测定肿瘤坏死因子-α(TNF-α),通过化学方法及酶法测定代谢参数来评估游离脂肪酸(FFAs)。
与鱼油相比,6-姜酚能更显著地增强磷酸化AMPK-α1,并通过上调Sirt-6和下调抵抗素降低P65,且比鱼油处理组更能减轻炎症分子P65、FFAs和TNF-α,但差异无统计学意义,这些作用伴随着显著的降血糖作用。
姜酚治疗通过靶向AMPK-NF-κB通路,增加SIRT-6并显著降低抵抗素水平,有效调节了HFD组的炎症优势状态和代谢紊乱。