Proanthocyanidins from Grape Seeds Modulate the NF-κB Signal Transduction Pathways in Rats with TNBS-Induced Ulcerative Colitis

Abstract

To elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE), we explore whether GSPE regulates the inflammatory response of TNBS-induced colitis in rats at the levels of NF-κB signal transduction pathway. Rats were intragastrically administered of different doses of GSPE (100, 200 and 400 mg·kg−1) per day for seven days after ulcerative colitis (UC) was induced by intracolonic injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Sulfasalazine (SASP) at 400 mg/kg was used as a positive control drug. The expression of nuclear factor-kappa B (NF-κB), phospho-I kappaB-alpha (pIκBα), inhibitor kappa B kinase (IκK) in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA) methods. Treatment with GSPE reduced the expression of NF-κB, pIκBα and IκK in the colon. The results of this study show that GSPE exerts beneficial effects in inflammatory bowel disease by inhibition of NF-κB signal transduction pathways.

The Gastrointestinal Tract as a Key Target Organ for the Health-Promoting Effects of Dietary Proanthocyanidins

“…As a consequence of these events, the animal treated with the extract exhibited a lower neutrophil infiltration in their colonic mucosa, a decrease of IL-1β concentration, lipid peroxidation, and colonic inducible nitric oxide synthase activity, while the concentrations of IL-2 and IL-4, the antioxidants enzymes activities, and the levels of glutathione increased. These effects were comparable to those obtained with sulfasalazine, the standard drug used for IBD treatment (201–204). …”

“…Grape seed extract (containing PACs >95%, dimeric >1.8%, oligomers >60%) also exerted a protective effect in recurrent colitis induced by the intracolonic injections of 2,4,6-trinitrobenzene sulfonic acid, reducing the colonic weight/length ratio and the microscopic and macroscopic damage scores (201–204). Such effect relied on the antiinflammatory and antioxidant properties of the extract, as it was shown to inhibit the NF-κB signaling pathway, reducing the expression levels of TNF-α, p-IKKα/β, p-IκBα, and the translocation of NF-κB to the nucleus of colonic epithelial cells (203, 204).…”

“…Such effect relied on the antiinflammatory and antioxidant properties of the extract, as it was shown to inhibit the NF-κB signaling pathway, reducing the expression levels of TNF-α, p-IKKα/β, p-IκBα, and the translocation of NF-κB to the nucleus of colonic epithelial cells (203, 204). As a consequence of these events, the animal treated with the extract exhibited a lower neutrophil infiltration in their colonic mucosa, a decrease of IL-1β concentration, lipid peroxidation, and colonic inducible nitric oxide synthase activity, while the concentrations of IL-2 and IL-4, the antioxidants enzymes activities, and the levels of glutathione increased.…”

Ferulic acid ameliorates TNBS-induced ulcerative colitis through modulation of cytokines, oxidative stress, iNOs, COX-2, and apoptosis in laboratory rats

“…It has been reported that activated phagocytic leukocytes have an ability to produce superoxide radicals that eventually leads to the production of reactive hydroxyl radical and peroxide (Adil et al, 2014[1]; Aswar et al, 2015[3]). Administration of TNBS may disrupt the endogenous antioxidant defense system leading to colonic oxidative damage (Li et al, 2011[47]). Superoxide dismutase (SOD) is an endogenous enzyme, whereas glutathione (GSH), a non-enzymatic antioxidant and both together play a vital role in cellular defense against elevated H 2 O 2 generation (Kandhare et al, 2015[29]).…”

“…Colitis was induced according to the procedure described elsewhere (Li et al, 2011[47]). Briefly, rats were slightly anaesthetized with ether following a 24 h fast, and then TNBS dissolved in 50 % ethanol was instilled into the colon of the animals (100 mg in a volume of 0.25 mL) using a medical-grade polyurethane catheter for enteral feeding (external diameter 2 mm) inserted 8 cm into the anus.…”