Background Rheumatic manifestation such as arthritis, spondylitis are the most common frequent extra-intestinal manifestations of inflammatory bowel disease (IBD), affecting 6 to 46% of patients. IBD is an umbrella term with two most prevalent entities namely Crohn's disease and Ulcerative colitis, defined as idiopathic chronic, relapsing and remitting inflammatory condition of intestinal tract. MMP-9, a matrixin is involved in the degradation of extracellular matrix promoting inflammation. Studies on MMP-9 knockout mice illustrated protection from collagen induced rheumatoid arthritis (RA) and Dextran sulphate sodium (DSS) induced colitis. Furthermore elevated MMP9 levels can be found in the synovial fluid of RA patients as well as IBD patients signifying that targeting MMP9 may have therapeutic importance. Mangiferin, an active component of Mango has demonstrated anti-inflammatory effects in the treatment of rheumatoid arthritis with low side-effects [1,2]; but its usefulness in chronic remission and relapse phases of human IBD i.e. chronic DSS model have not screened till date.
Objectives We investigated the therapeutic potential of Mangiferin; in a clinical relevant chronic model of DSS induced colitis in mice.
Methods Female BALB/c mice (8 to 12 wks) were randomized into four groups. Colitis was induced by cyclical administration of 5% DSS to mice i.e. 3 cycles of DSS with every cycle consisting of 7 days DSS followed by 7 days of autoclaved drinking water (7D DSS + 7D water). Group I (Normal control): free access to autoclaved drinking water. Group II (DSS control): free access to 5% DSS. Group III (DSS + Mangiferin_30mg/kg): free access to 5% DSS + oral Mangiferin at 30mg/kg. Group IV (DSS + Mangiferin_60mg/kg): free access to 5% DSS + oral Mangiferin at 60mg/kg. Mangiferin treatment was initiated following second cycle of DSS (i.e. Day 21); after assuring that colitis relapsed in mice. One fragment of the colon was fixed in 10% neutral buffered formalin for microscopic examination while the remaining tissue was divided into parts and stored at -70°C for assessment of biochemical markers of oxidative stress and inflammatory cytokines such as TNF-α, IL-1β, MMP-9.
Results Mangiferin treatment ameliorated the clinical parameters (body weight loss, stool consistency, occult blood), reduced microscopic damage (re-established mucosal architecture, abridged neutrophil infiltration), restored epithelial barrier integrity (diminished goblet cell loss), attenuated biochemical markers of oxidative stress (GSH, CAT, SOD, MDA, MPO), crucial inflammatory cytokines TNF-α, IL-1β and attenuates MMP-9 levels implicated in the pathogenesis of arthritis and IBD.
Conclusions Considering the beneficial effects of Mangiferin in arthritis and IBD, we suggest that it would be valuable to use Mangiferin in IBD patients with arthritis as its extra-intestinal manifestation.
Luczkiewicz, P., et al., Mangiferin: A promising therapeutic agent for rheumatoid arthritis treatment. Med Hypotheses, 2014. 83(5): p. 570–4.
Tsubaki, M., et al., Mangiferin suppresses CIA by suppressing the expression of TNF-alpha, IL-6, IL-1beta, and RANKL through inhibiting the activation of NF-kappaB and ERK1/2. Am J Transl Res, 2015. 7(8): p. 1371–81.
Disclosure of Interest None declared