Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms

Int Immunopharmacol. 2016 Sep:38:153-66. doi: 10.1016/j.intimp.2016.04.043. Epub 2016 Jun 6.

Abstract

New treatments for inflammatory bowel disease are of interest due to high rate of remission failure. Natural products have been effective in IBD therapeutics as they have multiple constituents. The aim of the present study was to evaluate the effect of Flaxseed extract (Fs.Cr) on ulcerative colitis and identify the possible mechanisms involved. Colitis was induced by intrarectal administration of 6% AA in BALB/c mice. Colonic mucosal damage was assessed after 24h by calculating disease activity index (DAI), macroscopic and histological damage scores, biochemical measurement of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total glutathione activities. Since cytokines are involved in exacerbating inflammatory cascade with emerging role of innate immune cytokines in IBD therapeutics, we hence assessed the effect on the levels of TNF-α, IFN-γ and IL-17, at 6, 12 and 24h by ELISA. Fs.Cr ameliorated the severity of AA colitis as evident by improved DAI, macroscopic damage and the histopathological scores along with restoration of goblet cells. Fs.Cr decreased MDA and MPO activities and enhanced antioxidant activity compared to the AA group. Finally, Fs.Cr in doses (300 and 500mg/kg) decreased TNF-α and IFN-γ levels at all time points with simultaneous increase in IL-17 levels at 24h as compared to the AA group. These results suggest that Fs.Cr ameliorates the severity of AA colitis by reducing goblet cell depletion, scavenging oxygen-derived free radicals, reduce neutrophil infiltration that may be attributed due to decreasing IFN-γ and TNF-α and increasing IL-17 levels.

Keywords: Goblet cells; IL-17, IFN-gamma; Innate immune arm; Natural products; Ulcerative colitis.

MeSH terms

  • Acetic Acid
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colon / drug effects*
  • Colon / immunology
  • Colon / pathology
  • Cytokines / metabolism
  • Flax / immunology*
  • Humans
  • Immunity, Mucosal / drug effects
  • Inflammatory Bowel Diseases / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Peroxidase / metabolism
  • Plant Extracts / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Plant Extracts
  • Peroxidase
  • Acetic Acid