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.