Protective effect of Morus macroura Miq. fruit extract against acetic acid-induced ulcerative colitis in rats: Involvement of miRNA-223 and TNFα/NFκB/NLRP3 inflammatory pathway

Abstract

Tumor necrosis factor receptor (TNFR) activation and nuclear factor kappa B (NF{kappa}B) expression play a significant role in the activation of nod-like receptor pyrin domain-1 containing 3 (NLRP3) inflammasome inflammatory pathway, which is involved in the pathogenesis of ulcerative colitis (UC). Furthermore, miRNA-223 expression was shown to exert counter-regulatory effect on NLRP3 expression. Interestingly, polyphenols are attaining increased importance for their potential effectiveness in ameliorating certain diseases owing to their antioxidant and anti-inflammatory activity. In accord, our study attempted to investigate the effect of mulberry tree (Morus macroura) fruit extract (MFE) against acetic acid (AA)- induced UC in rats, which is not previously investigated, based on previous promising results for MFE in alleviating gastric ulcer in rats. First, total phenolic (TPC), total flavonoid (TFC), and total anthocyanin content (TAC) were determined in MFE. Then, MFE (300 mg/kg) and sulfasalazine (Sulfa), as a standard treatment (100 mg/kg), were given orally for seven days before intra-rectal induction of UC by AA (2 ml, 4% v/v) on day eight. The extent of UC was evaluated macroscopically and microscopically. Biochemically, the colonic TNFR1, NLRP3, p- NF{kappa}B p65, TNF, interleukin-1 beta (IL-1{beta}), IL-18 levels, miRNA-223 expression and caspase-1 activity were assayed. MFE significantly reduced macroscopic and microscopic scores, colonic levels of TNFR1, NLRP3, p-NF{kappa}B p65, TNF, IL-1{beta}, IL-18, and caspase-1 activity, and showed increased miRNA-223 expression, almost similarly to Sulfa effects. In conclusion, our study provided a novel impact for MFE against AA-induced UC in rats through affecting miRNA-223 expression and halting TNF/NF{kappa}B/NLRP3 inflammatory pathway.