Therapeutic effect and mechanism of proanthocyanidins from grape seeds in rats with TNBS-induced ulcerative colitis

Abstract

The aim of the study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seeds (GSPE) in the treatment of ulcerative colitis (UC). Rats were intragastrically administered different doses of GSPE (100, 200, and 400 mg/kg) per day for 7 days after UC was twice-induced by intracolonic injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS)dissolved in 50% ethanol. Sulfasalazine (SASP) at 200 mg/kg was used as a positive control drug. Macroscopic and microscopic damage scores and changes in weight/length ratio (mg/mm) of colon segments were analyzed. The levels of malonyldialdehyde (MDA), interleukin (IL)-1beta, IL-2, IL-4, and myeloperoxidase (MPO) activity in the colon tissues and MPO activity in the serum were all measured by biochemical methods or double antibody sandwich ELISA methods. Compared with the TNBS control group, GSPE treatment facilitated recovery of pathologic changes in the colon after insult with TNBS, as demonstrated by increased body weight (p < 0.01) and decreased colonic weight/length ratio (p < 0.01); GSPE also notably reduced the colonic macroscopic and microscopic damage scores (p < 0.01). The MPO activity in colon tissues and serum of rats treated with GSPE was significantly lower than that in the TNBS control group. The MDA and IL-1beta levels of colon tissues were also decreased in GSPE groups. The intestinal antiinflammatory effect of GSPE was accompanied by a significant improvement of IL-2 and IL-4 levels in the colon tissues of rats in the high-dose GSPE group (p < 0.05). Compared with the SASP group, GSPE groups had no significant difference in the therapeutic effect (p > 0.05). GSPE exerts a beneficial antiinflammatory effect in the acute phase of TNBS-induced colitis in rats by downregulating some of the mediators involved in the intestinal inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, decreasing production of proinflammatory cytokines IL-1beta, and increasing production of antiinflammatory cytokines IL-2 and IL-4.

Proanthocyanidins from grape seeds modulates the nuclear factor-kappa B signal transduction pathways in rats with TNBS-induced recurrent ulcerative colitis

“…The dosage of SASP or GSPE was 10 mL/kg, once daily, for a total of 7 days. These dosages were chosen on the basis of a previous study, as they were the most active in preventing acetic acid or TNBS induced acute colitis in rats [16,17].…”

Grape seed proanthocyanidin extract (GSPE) differentially regulates Foxp3+ regulatory and IL-17+ pathogenic T cell in autoimmune arthritis

“…Their pharmacological properties are related to an increase of tonicity and resistance of capillary walls (making them more resistant to the degradative action of elastase and collagene) and to radical scavenging and inhibition of superoxide ion formation [18,19]. GSPE has shown a beneficial anti-inflammatory effect in animal models of colitis, skin tumor, and autoimmune arthritis [20][21][22].…”

NaOH-Induced Crohn’s Colitis in Rats: A Novel Experimental Model

“…This evidence suggests that this model is histopathologically relevant to the features of CD, but not UC. However, in most experimental studies, this has been widely used as a model of UC [11][12][13]. In our model, histopathological examinations revealed transmural inflammation with focal ulcerations.…”