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

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.

Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies

“…The number of Bcl-2-and caspase 3-positive cells were significantly decreased in the intestine of NEC protocol exposed rats that were orally treated with sesamol compared to non-treated rats [125]. Enteral administration of curcumin in a rat NEC model decreased intestinal protein and mRNA expression of caspase 1 and NLRP3 in a SIRT1 mediated fashion, suggesting curcumin reduces pyroptosis [124].…”

“…Bacteroides fragilis ZY-312 [113] Lactobacillus reuteri DSM 17938 [68,69] Lactobacillus reuteri ATCC PTA 4659 [68] Lactobacillus reuteri biofilm on unloaded microspheres [71,72] Lactobacillus reuteri biofilm on MRS loaded microspheres [71] Lactobacillus reuteri biofilm on sucrose loaded microspheres [72] Lactobacillus reuteri biofilm on maltose loaded microspheres [72] Bifidobacterium microcapsules [114] Bifidobacterium mixture [115] Bifidobacterium adolescentis [76] Bifidobacterium infantis [116] Bifidobacterium bifidum OLB6378 [74] Bifidobacterium breve M-16V [117] Lactobacillus rhamnosus HN001 (live) [39] Lactobacillus rhamnosus HN001 (dead) [39] Lactobacillus rhamnosus isolated DNA [39] Probiotic mixture (Bifidobacterium animalis DSM15954, Lactobacillus acidophilus DSM13241, Lactobacillus casei ATCC55544, Lactobacillus pentosus DSM14025 and Lactobacillus plantarum DSM13367) [77] CpG-DNA [39] Other interventions Bovine milk exosomes [118] Native human breast milk exosomes [78,119] Pasteurized human breast milk exosomes [119] Preterm human breast milk exosomes [120] Ginger [121] Fennel seed extracts [122] Amniotic fluid [40,63,123] Curcumin [124] Sesamol [125] Astragaloside iv [126] Resveratrol [127] Berberine [79] Surfactant protein a [80] Human β-defensin-3 [81] PUFA, polyunsaturated fatty acids; MPL milk polar lipids; MFGM, milk fat...…”

“…In a preterm pig NEC model, enteral treatment with amniotic fluid reduced the distal small intestinal mRNA expression of IFNγ, IL1α and TNFα and middle small intestinal mRNA expression of IL1α, TNFα, IL6 and IL8 compared to formula fed pigs that developed NEC [123]. Oral administration of curcumin dose dependently reduced intestinal protein levels of IL1β, IL6, IL1, TNFα and protein and mRNA levels of TLR4 while increasing protein and mRNA levels of SIRT1 and nuclear factor erythroid 2-relatedfactor 2 (NRF2) [124]. In a rat NEC model, addition of surfactant protein A to formula feeding reduced ileal IL1β, TNFα and TLR4 protein levels, but did not affect ileal IFNγ concentrations [80].…”

“…Intestinal IL1β (protein) ↓ [124] Intestinal IL6 (protein) ↓ [124] Intestinal IL18 (protein) ↓ [124] Intestinal TNFα (protein) ↓ [124] Intestinal TLR4 (protein) ↓ [124] Intestinal SIRT1 (protein) ↑ [124] Intestinal NRF2 (protein) ↑ [124] Intestinal TLR4 (mRNA) ↓ [124] Intestinal SIRT1 (mRNA) ↑ [124] Intestinal NRF2 (mRNA) ↑ [124] Surfactant protein A HGF, hepatocyte growth factor; TGF-β1, transforming growth factor β1; IGF1, insulin-like growth factor 1; ATRA, all-trans-retinoic acid.…”

“…Intestinal caspase 1 (protein) ↓ [124] Intestinal NLRP3 (protein) ↓ [124] Intestinal caspase 1 (mRNA) ↓ [124] Intestinal NLRP3 (mRNA) ↓ [124] ↑ depicts an increase, ↓ depicts a decrease; PUFA, polyunsaturated fatty acids; MPL, milk polar lipids; HMO, human milk oligosaccharides; EGF, epidermal growth factor; HB-EGF, hemoglobin-binding EGF-like growth factor; EPO, erythropoietin; ATRA, all-trans retinoic acid.…”