Protective effect ofMorus macrouraMiq. 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 (NFκB) 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- NFκB p65, TNFα, interleukin-1 beta (IL-1β), 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-NFκB p65, TNFα, IL-1β, 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 TNFα/NFκB/NLRP3 inflammatory pathway.

A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18)

“…Stimulation of p-NF-κB p65 initially activates NLRP3 inflammasome and Caspase-1 and stimulates IL-1β and IL-18, which in turn triggers the production of other inflammatory cytokines including IL-6 and TNF-α [ 39 ]. The current study showed that intrarectal administration of AA significantly elevated colon IL-18, which is consistent with the aforementioned findings of a previous study [ 40 ], in which intrarectal administration of AA increased colon level of IL-18 through upregulation of the TNFα/NF-κB/NLRP3 inflammatory pathway. This study reported that oral administration of DAPA for 14 days significantly declined IL-18 levels in colon tissues confirming former results of Leng et al, (2016) [ 41 ], in which intragastric administration of DAPA 1.0 mg/kg/day for 12 weeks decreased the production of IL-1β and IL-18 proteins in abdominal aorta of diabetic mice.…”