Preventive effect of bergenin against the development of TNBS-induced acute colitis in rats is associated with inflammatory mediators inhibition and NLRP3/ASC inflammasome signaling pathways.

Ulcerative colitis is an idiopathic inflammatory bowel disease characterized by intestinal inflammation; blocking this inflammatory process may be the key to the development of new naturally occurring anti-inflammatory drugs, with greater efficiency and lower side effects. The objective of this study is to explore the effects of bergenin (BG) in TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced acute colitis model in rats in order to assist in the studies for the development of novel natural product therapies for inflammatory bowel disease. 48 Wistar rats were randomized into six groups: (i) Control and (ii) TNBS control; (iii) 5-ASA 100 mg/kg/day (iv) BG 12 mg/kg/day (v) BG 25 mg/kg/day and (vi) BG 50 mg/kg/day. Colitis was induced by instillation of TNBS. Colitis was evaluated by an independent observer who was blinded to the treatment. Our results revealed that bergenin decreased the macroscopic and microscopic damage signs of colitis, and reduced the degree of neutrophilic infiltration in the colon tissue; also, it was capable to down-regulate COX-2, iNOS, IkB-α, and pSTAT3 protein expression. Similarly, using a protocol for indirect ELISA quantification of cytokines, bergenin treatment reduced IL-1ß, IFN-γ and IL-10 levels, and inhibited both canonical (IL-1) and non-canonical (IL-11) NLRP3/ASC inflammasome signaling pathways in TNBS-induced acute colitis. Conclusion: Our study has provided evidence that administration of bergenin reduced the damage caused by TNBS in an experimental model of acute colitis in rats, reduced levels of pro-inflammatory proteins and cytokines probably by modulation of pSTAT3 and NF-κB signaling and blocking canonical and non-canonical NLRP3/ASC inflammasome pathways.

Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. AIM OF THE STUDY: In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. MATERIALS AND METHODS: ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. RESULTS: TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50 mg/kg) administration reduced COX-2 overexpression. CONCLUSIONS: We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases.