Abstract
Background and Aims: Surgery remains the major available strategy in inflammatory bowel disease (IBD) fibrotic strictures because no available drugs have sufficient prevention and treatment in this complication. This study aimed to evaluate the efficacy of the total flavone of Abelmoschus manihot L. Medic (TFA) on the development of colonic fibrosis in mice and its possible mechanism. Methods: The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colonic inflammation-associated fibrosis mice were used to evaluate anti-fibrosis of TFA using macroscopic, histological, immunohistochemical analyses, ELISA, Masson staining, Verhoeff’s von Gieson staining, transcription-quantitative polymerase chain reaction, and immunoblot analysis. Results: Oral administration of TFA attenuated body weight loss, reduced colon length shortening, lowered the morphological damage index score, and notably ameliorated the inflammatory response. TFA downregulated proinflammatory cytokines IL-6, IL-17, TNF-α, IFN-γ productions, and increased the levels of anti-inflammatory cytokine IL-10 and TGF-β. The histological severity of the colonic fibrosis was also notably improved by the TFA treatment and associated with a significant reduction in the colonic expression of col1a2, col3a2, and hydroxyproline. TFA inhibits α-SMA, TGF-β, vimentin, TIMP-1 expression, increasing MMPs, thereby inhibiting activated intestinal mesenchymal cells and extracellular matrix (ECM) deposition. Conclusion: Together, we herein provide the evidence to support that TFA may restore the imbalance of Th17/Treg and decrease the generation of ECM. This may be a potential mechanism by which TFA protects the intestine under inflammatory conditions and acts as a therapeutic agent for the treatment of intestinal fibrosis in Crohn’s disease.
Highlights
Crohn’s disease (CD) is a chronic inflammatory bowel disease that affects any part of the gastrointestinal tract, and its prevalence has increased annually worldwide
The TNBS-induced chronic colitis mice model was employed to evaluate the effect of TFA
A marked progressive weight loss and disease activity index (DAI) score increase was observed in TNBS-induced mice compared with the sham-1, sham-2 groups, while treatment with TFA in modeling or after modeling showed significantly reversed body weight loss (Figure 1A) and DAI score (Figure 1B)
Summary
Crohn’s disease (CD) is a chronic inflammatory bowel disease that affects any part of the gastrointestinal tract, and its prevalence has increased annually worldwide. Population-based cohort studies showed that up to 40% of patients with CD will develop intestinal fibrosis, which involves all intestinal layers and lead to strictures and even intestinal obstruction (Peyrin-Biroulet et al, 2010; Cosnes et al, 2011). Fibrogenesis is an adaptive response to the onset of inflammation and facilitates tissue repair, whereas fibrosis is an exaggerated response to chronic inflammation and leads to excessive scarring characterized by profound production and deposition of extracellular matrix (ECM). The fibrosis will occur when ECM production is increased and surpasses degradation (Rieder et al, 2017). Medic (TFA) on the development of colonic fibrosis in mice and its possible mechanism
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