Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and anti-inflammatory mechanisms.

Key Findings

Inflammatory bowel disease (IBD) comprises of Ulcerative colitis (UC) and Crohn’s disease (CD). The cytokines involved in the inflammation of IBD are tumour necrosis factor (TNF) -α, interferon (IFN) -γ, interleukin (IL) -8, IL1-β and IL-12. The primary objective of the study was to assess the effectiveness of a crude aqueous methanolic extract of flaxseed in acetic acid (AA) induced colitis model in mice. The AA colitis model was used because it is an easy and reproducible method in laboratory for induction of colitis and resembles human features of UC with alteration of cytokines causing inflammation and oxidative stress. The aqueous methanolic extract reduced the severity of acetic acid induced colitis model in mice by reducing IFN-γ, TNF-α and increasing IL-17 levels with simultaneous antioxidant and anti-inflammatory activities that result in mucosal protective effects.

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 24 h 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 24 h 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 500 mg/kg) decreased TNF-α and IFN-γ levels at all time points with simultaneous increase in IL-17 levels at 24 h as compared to the AA group. These results suggest that Fs.Crameliorates 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.