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

• Published in: Basic & clinical pharmacology & toxicology Vol. 110; no. 3; pp. 238 - 244
• Main Authors: Li, Xiao-Hong, McGrath, Kristine C-Y, Nammi, Srinivas, Heather, Alison K., Roufogalis, Basil D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2012; Blackwell
• Subjects: Amyloid; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cell culture; Cells, Cultured; Cytokines - metabolism; Diet, High-Fat - adverse effects; Gene expression; Gene Expression Regulation - drug effects; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; High fat diet; Humans; I Kappa B kinase; IKK protein; Inflammation; Inflammation - drug therapy; Inflammation - physiopathology; Interleukin 1; Interleukin 6; Interleukin 8; Liver; Liver - drug effects; Liver - physiopathology; Male; Medical sciences; Molecular modelling; NF- Kappa B protein; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Nuclear transport; Pharmacology. Drug treatments; Plant Extracts - pharmacology; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Signal transduction; Signal Transduction - drug effects; Tumor necrosis factor- alpha; Western blotting; Zingiber officinale; Zingiber officinale - chemistry; Monocotyledones; Nutrition; Rat; Digestive system; Pharmacognosy; Liver; Rodentia; Lipids; Inflammation; Medicinal plant; Feeding; Vertebrata; Mammalia; Diet; Animal; Angiospermae; Fat; Flavoring crop; Attenuation; Spermatophyta; Inhibitor; Zingiber officinale; Zingiberaceae
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2011.00791.x

:  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‐κB)‐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‐κB activation were measured by real‐time PCR, Western blot and an NF‐κB nuclear translocation assay, respectively. In vitro, cell culture studies were carried out in human hepatocyte (HuH‐7) cells by treatment with Zingiber officinale (100 μg/mL) for 24 hr prior to interleukin‐1β (IL‐1β, 8 ng/mL)‐induced inflammation. We showed that Zingiber officinale treatment decreased cytokine gene TNFα and IL‐6 expression in HFD‐fed rats, which was associated with suppression of NF‐κB activation. In vitro, Zingiber officinale treatment decreased NF‐κB‐target inflammatory gene expression of IL‐6, IL‐8 and serum amyloid A1 (SAA1), while it suppressed NF‐κB activity, IκBα degradation and IκB 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‐κB activation. The study demonstrates that the anti‐inflammatory effect of Zingiber officinale occurs at least in part through the NF‐κB signalling pathway.