Morus macroura Miq. Fruit extract protects against acetic acid-induced ulcerative colitis in rats: Novel mechanistic insights on its impact on miRNA-223 and on the TNFα/NFκB/NLRP3 inflammatory axis

Food Chem Toxicol. 2022 Jul:165:113146. doi: 10.1016/j.fct.2022.113146. Epub 2022 May 18.

Abstract

Nod-like receptor pyrin domain-1 containing 3 (NLRP3) inflammasome/tumor necrosis factor alpha (TNFα)/nuclear factor kappa B (NFκB) inflammatory pathway is known to be involved in the pathogenesis of ulcerative colitis (UC). Inversely, miRNA-223 can exert counter-regulatory effect on NLRP3 expression. The mulberry tree (Morus macroura) fruit is attaining increased importance for its antioxidant and anti-inflammatory activity in addition to its high safety profile. Accordingly, we attempted to explore the possible protective effect of mulberry fruit extract (MFE) in acetic acid (AA)-induced UC rat model. Phytochemical constituents of MFE were characterized using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). In the in vivo study, three doses of MFE were orally given for seven days before intra-rectal induction of UC by AA on day eight. Screening study revealed that MFE (300 mg/kg) significantly reduced macroscopic and microscopic UC scores. Biochemically, MFE ameliorated oxidative stress, levels of TNFR1, NLRP3, p-NFκB p65, TNFα, IL-1β, and IL-18, caspase-1 activity, but enhanced miRNA-223 expression. In conclusion, our study provided a novel protective impact for MFE against UC, in which miRNA-223 and TNFα/NFκB/NLRP3 pathway are involved. These results provide a promising step that might encourage further investigations of MFE as a protective agent in UC patients.

Keywords: Mulberry fruit; NLRP3; TNFα/NFκB; Ulcerative colitis; miRNA-223.

MeSH terms

  • Acetic Acid / analysis
  • Animals
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / prevention & control
  • Fruit / chemistry
  • Humans
  • Inflammasomes / metabolism
  • MicroRNAs* / genetics
  • Morus*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Plant Extracts / analysis
  • Rats
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Inflammasomes
  • MIRN223 microRNA, human
  • MIRN223 microRNA, rat
  • MicroRNAs
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Acetic Acid