Attenuation of Liver Pro-Inflammatory Responses by Zingiber officinale via Inhibition of NF-kappa B Activation in High-Fat Diet-Fed Rats

The aim of this study was to investigate whether treatment with a ginger (Zingiber officinale) extract of high-fat diet (HFD)-fed rats suppresses Nuclear factor-kappa B (NF-kappa B)-driven hepatic inflammation and to subsequently explore the molecular mechanisms in vitro. Adult male Sprague-Dawley rats were treated with an ethanolic extract of Zingiber officinale (400 mg/kg) along with a HFD for 6 weeks. Hepatic cytokine mRNA levels, cytokine protein levels and NF-kappa B activation were measured by real-time PCR, Western blot and an NF-kappa B nuclear translocation assay, respectively. In vitro, cell culture studies were carried out in human hepatocyte (HuH-7) cells by treatment with Zingiber officinale (100 mu g/mL) for 24 hr prior to interleukin-1 beta (IL-1 beta, 8 ng/mL)-induced inflammation. We showed that Zingiber officinale treatment decreased cytokine gene TNF alpha and IL-6 expression in HFD-fed rats, which was associated with suppression of NF-kappa B activation. In vitro, Zingiber officinale treatment decreased NF-kappa B-target inflammatory gene expression of IL-6, IL-8 and serum amyloid A1 (SAA1), while it suppressed NF-kappa B activity, I kappa B alpha degradation and I kappa B kinase (IKK) activity. In conclusion, Zingiber officinale suppressed markers of hepatic inflammation in HFD-fed rats, as demonstrated by decreased hepatic cytokine gene expression and decreased NF-kappa B activation. The study demonstrates that the anti-inflammatory effect of Zingiber officinale occurs at least in part through the NF-kappa B signalling pathway.