6-Gingerol modulates proinflammatory responses in dextran sodium sulfate (DSS)-treated Caco-2 cells and experimental colitis in mice through adenosine monophosphate-activated protein kinase (AMPK) activation

Food Funct. 2015 Oct;6(10):3334-41. doi: 10.1039/c5fo00513b.

Abstract

Background: 6-gingerol has been reported to have anti-inflammatory effects in different experimental settings. The present study aimed at evaluating the effect of 6-gingerol on dextran sodium sulfate (DSS)-induced barrier impairment and inflammation in vitro and in vivo.

Methods: a differentiated Caco-2 monolayer was exposed to DSS and treated with different concentrations of 6-gingerol (0, 1, 5, 10, 50, and 100 μM). Changes in intestinal barrier function were determined using transepithelial electrical resistance (TEER). The anti-inflammatory activity of 6-gingerol was examined as changes in the expression of proinflammatory cytokine using quantitative real-time PCR. Western blotting was employed to determine the activation of adenosine monophosphate-activated protein kinase (AMPK). Mice with DSS-induced colitis were given different oral dosages of 6-gingerol daily for 14 days. Body weight and colon inflammation were evaluated, and level of proinflammatory cytokines in colon tissues was measured.

Results: 6-gingerol treatment was shown to restore impaired intestinal barrier function and to suppress proinflammatory responses in DSS-treated Caco-2 monolayers. We found that AMPK was activated on 6-gingerol treatment in vitro. In animal studies, 6-gingerol significantly ameliorated DSS-induced colitis by restoration of body weight loss, reduction in intestinal bleeding, and prevention of colon length shortening. In addition, 6-gingerol suppressed DSS-elevated production of proinflammatory cytokines (IL-1β, TNFα, and IL-12).

Conclusion: our findings highlight the protective effects of 6-gingerol against DSS-induced colitis. We concluded that 6-gingerol exerts anti-inflammatory effects through AMPK activation. It is suggested that 6-gingerol has a promising role in treatment of IBD.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Caco-2 Cells
  • Catechols / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colon / drug effects
  • Colon / metabolism
  • Dextran Sulfate / toxicity*
  • Disease Models, Animal
  • Fatty Alcohols / pharmacology*
  • Female
  • Humans
  • Inflammation / drug therapy
  • Interleukin-12 / metabolism
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Catechols
  • Fatty Alcohols
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Dextran Sulfate
  • gingerol
  • AMP-Activated Protein Kinases