Curcumin improves necrotising microscopic colitis and cell pyroptosis by activating SIRT1/NRF2 and inhibiting the TLR4 signalling pathway in newborn rats

Innate Immun. 2020 Oct;26(7):609-617. doi: 10.1177/1753425920933656. Epub 2020 Sep 13.

Abstract

This study aimed to explore comprehensively the biological function of curcumin, and its underlying mechanism, in protecting from necrotising microscopic colitis in newborn rats. A total of 20 normal healthy rats were selected, and a necrotising enterocolitis (NEC) model was established. After hypoxia and hypothermia stimulation, these rats were treated with different doses of curcumin (control group, NEC model group, NEC+20 mg/kg curcumin and NEC+50 mg/kg curcumin). Inflammation was identified using hematoxylin and eosin staining, and inflammatory factors were detected via ELISA. The mRNA and protein levels of SIRT1, NRF2, TLR4, NLRP3 and caspase-1 were determined by quantitative RT-PCR and Western blotting, respectively. Curcumin improved the inflammatory condition of NEC and inhibited the expression of inflammatory factors in NEC newborn rat intestinal tissue. Furthermore, the SIRT1/NRF2 pathway was inhibited in the intestinal tissue of NEC newborn rats, whereas curcumin treatment induced the activation of the SIRT1/NRF2 pathway and inhibited TLR4 expression in these animals. In addition, curcumin could also inhibit the expression of inflammatory factors and alleviate the LPS/ATP-induced focal death pathway in intestinal epithelial cells through the SIRT1 pathway. Curcumin can improve necrotising microscopic colitis and cell pyroptosis by attenuating NEC-induced inhibition of SIRT1/NRF2 and inhibiting the TLR4 signalling pathway in newborn rats.

Keywords: Curcumin; SIRT1/NRF2; TLR4; cell pyroptosis; necrotising microscopic colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cells, Cultured
  • Colitis, Microscopic / therapy*
  • Colon / metabolism
  • Colon / pathology*
  • Curcumin / therapeutic use*
  • Disease Models, Animal
  • Humans
  • NF-E2-Related Factor 2 / metabolism*
  • Necrosis
  • Pyroptosis
  • Rats
  • Sirtuin 1 / metabolism*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Sirtuin 1
  • Curcumin