Proanthocyanidins from Grape Seeds Modulates the Nuclear Factor-kappa B Signal Transduction Pathways in Rats with TNBS-induced Recurrent Ulcerative Colitis

The aim of this study was to elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE) on recurrent ulcerative colitis (UC) in rats. GSPE in doses of 100, 200, and 400mg/kg were intragastrically administered per day for 7 days after recurrent colitis was twice-induced by TNBS. The levels of GSH, as well as the activity of GSH-Px and SOD in colon tissues were measured by biochemical methods. The expression levels of tumor necrosis factor-α (TNF-α) and the nuclear translocation levels of nuclear factor-kappa B (NF-κB) in the colon tissues were measured by enzyme-linked immunosorbent assay methods. Western blotting analysis was used to determine the protein expression levels of inhibitory kappa B-alpha (IκBα), inhibitor kappa B kinase (IKKα/β), phosphorylated IκBα and phosphorylated IKKα/β. GSPE treatment was associated with a remarkable increased the activity of GSH-Px and SOD with GSH levels in TNBS-induced recurrent colitis rats as compared to the model group. GSPE also significantly reduced the expression levels of TNF-α, p-IKKα/β, p-IκBα and the translocation of NF-κB in the colon mucosa. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response and promoting damaged tissue repair to improve colonic oxidative stress. Moreover, GSPE inhibited the TNBS-induced inflammatory of recurrent colitis though blocking NF-κB signaling pathways.