الفهرس | Only 14 pages are availabe for public view |
Abstract Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. This study was carried out to investigate the potential therapeutic effect of the natural flavonoid galangin in a mouse model of dextran sulfate sodium (DSS)-induced colitis, and to elucidate the underlying mechanisms for its action. First, a 2-week dose-selection study was performed to choose the best therapeutic dose of galangin out of 3 doses (20, 40, and 80 mg/kg) in DSS-induced colitis. The medium dose was selected to be investigated in a 4-week mechanistic study, as it significantly improved disease activity index scores, ameliorated histopathological signs of colitis, and lowered nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase protein abundance. In the mechanistic study, galangin (40 mg/kg), sulfasalazine (100 mg/kg), and a combination of both (20 mg/kg galangin + 50 mg/kg sulfasalazine) were investigated in a 4-week mouse model of DSS-induced colitis. Administration of DSS caused a significant elevation in serum lactate dehydrogenase (LDH) activities, toll-like receptor 4 (TLR4) mRNA expression, NF-κB p65 nuclear translocation, tissue interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, and high mobility group box protein 1 (HMGB1) mRNA expression. This was accompanied by a reduction in the antioxidant reduced glutathione (GSH) and an elevation in malondialdehyde (MDA) levels. Treatment with galangin significantly lowered serum LDH activities, TLR4 and HMGB1 mRNA expression, NF-κB nuclear translocation, tissue IL-6 and TNF-α levels, consequently restoring GSH levels and lowering MDA levels. Galangin showed comparable therapeutic effect to sulfasalazine. Keywords: Inflammatory bowel diseases, ulcerative colitis, dextran sulfate sodium, toll-like receptor 4, galangin, sulfasalazine. |