ABSTRACT
Inflammatory bowel diseases involve chronic intestinal inflammation which is mostly caused by Crohn's disease and ulcerative colitis (UC) conditions. Patients having UC are prone to colorectal cancer and dysplastic polyps, and also have sporadic adenomas. Syringic acid (SA) possesses many health benefits including antioxidant, anti-bacterial, and anti-cancer. This study was aimed to identify the effects of SA on UC, using a murine experimental model. Clinical symptoms and weight loss were significantly reduced in mice induced with dextran sulfate sodium (DSS) and treated with SA, compared to untreated mice. The effects of SA exhibited in DSS-induced mice were associated with significant decrease in the expressions levels of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), pro-inflammatory cytokines (tumor necrosis factor [TNF-α], interleukin [IL-1ß and IL-6]), remarkable amelioration of colonic architectural disruption, and a significant reduction in the activity of colonic myeloperoxidase. To further confirm the anti-inflammatory property of SA, RAW 264.7 cells were stimulated with lipopolysaccharides. SA dose-dependently inhibited the cytokines TNF-α, IL-1ß, and IL-6. It also decreased the expressions of p65-NF-κB and IκB, thus reducing the activation and nuclear accumulation of p-STAT-3Y705 . This prohibited the degradation of inhibitory protein, IκB, as well as inhibited the nuclear translocation of p65-NF-κB in colonic tissue. It was concluded that SA has a potential to limit inflammation via inhibiting the p65-NF-κB and STAT3 signaling; hence it can be used for therapeutic purposes.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Gallic Acid/analogs & derivatives , Animals , Anti-Inflammatory Agents/pharmacology , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Colon/drug effects , Colon/metabolism , Colon/pathology , Cytokines/metabolism , Dextran Sulfate , Gallic Acid/pharmacology , Gallic Acid/therapeutic use , I-kappa B Kinase/metabolism , Lipopolysaccharides , Male , Mice , Mice, Inbred BALB C , Peroxidase/metabolism , RAW 264.7 Cells , STAT3 Transcription Factor/metabolism , Transcription Factor RelA/metabolismABSTRACT
The objective of the present work was to evaluate the anti-inflammatory effects of Vicenin-2 on dextran sulfate sodium (DSS)-induced colitis model. Colitis was induced in C57BL/6J mice by administration of 2% DSS in drinking water for 7 days. In addition to DSS, Vicenin-2 (50 mg kg-1 /day-1 ) was administrated orally to the test group. The ulceration extent and severity were assessed macroscopically, histopathologically, and by disease activity index. The Vicenin-2 treated group showed significant differences in physiological parameters including bodyweight, colon weight, and colon length, compared to DSS-induced colitis group. In addition, Vicenin-2 treatment effectively reduced stool consistency and bleeding scores. Myeloperoxidase (MPO) activity, expressions of pro-inflammatory cytokines, and specific key inflammatory markers (iNOS and COX-2) significantly increased in DSS-induced colitis colon tissues. However, administration of Vicenin-2 effectively reduced the MPO activity, attenuated the expression of pro-inflammatory cytokines and key inflammatory markers, in DSS-induced colitis mice. These results were comparable with sulfasalazine, an anti-inflammatory drug used routinely for ulcerative colitis (UC). These findings suggest that Vicenin-2 effectively suppresses DSS-induced colitis by attenuating expressions of key inflammatory mediators and found to be an attractive therapeutic drug for treating UC.
