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.

Abstract

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-1β, 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.

• Authors: Guilherme Antônio Lopes de Oliveira, Catalina Alarcón de la Lastra, Maria Ángeles Rosillo, Maria Luisa Castejon Martinez, Marina Sánchez-Hidalgo, Jand Venes Rolim Medeiros, Isabel Villegas
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 297 Pg. 25-33 (Jan 05 2019) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 30365937 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Benzopyrans
• CARD Signaling Adaptor Proteins
• Inflammasomes
• Inflammation Mediators
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Protective Agents
• Pycard protein, rat
• Trinitrobenzenesulfonic Acid
• bergenin

Topics

• Acute Disease
• Animals
• Benzopyrans (chemistry, pharmacology)
• CARD Signaling Adaptor Proteins (antagonists & inhibitors, metabolism)
• Colitis (chemically induced, drug therapy)
• Disease Models, Animal
• Inflammasomes (drug effects)
• Inflammation (drug therapy)
• Inflammation Mediators (pharmacology)
• Male
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors, metabolism)
• Protective Agents (chemistry, pharmacology)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Trinitrobenzenesulfonic Acid