Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling

Abstract

Naringenin, one of the most abundant flavonoids in citrus, grapefruits and tomatoes, has been used as a traditional anti-inflammatory agent for centuries. However, the molecular mechanism of naringenin in intestinal inflammation remains unknown so far. The present study investigated a molecular basis for the protective effect of naringenin in dextran sulphate Sodium-induced murine colitis. Pre-administration of naringenin significantly reduced the severity of colitis and resulted in down-regulation of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox2), TNF-α and IL-6 mRNA) in the colon mucosa. The decline in the production of pro-inflammatory cytokines, specifically TNF-α and IL-6, correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) mRNA and protein. Phospho-NF-κB p65 protein was significantly decreased, which correlated with a similar decrease in phospho-IκBα protein. Consistent with the in vivo results, naringenin exposure blocked lipopolysaccharide-stimulated nuclear translocation of NF-κB p65 in mouse macrophage RAW264.7 cells. In addition, in vitro NF-κB reporter assays performed on human colonic HT-29 cells exposed to naringenin demonstrated a significant inhibition of TNF-α-induced NF-κB luciferase expression. Thus, for the first time, the present study indicates that targeted inhibition of the TLR4/NF-κB signalling pathway might be an important mechanism for naringenin in abrogating experimental colitis.

Chitooligosaccharides Attenuate Lipopolysaccharideinduced Inflammation and Apoptosis of Intestinal Epithelial Cells: Possible Involvement of TLR4/NF-κB Pathway.

“…[21][22]27 At present, TLR4/ NF-κB pathway has been believed as a targets for IBD control. 28 The results of this study demonstrated that CHOS treatment significantly downregulated the enhanced expression of TLR4 and NF-κB induced by LPS, suggesting the possible involvement of this signal pathway in the protective role of CHOS against IBD. Interestingly, although IL-8 was also a pro-inflammatory cytokine involved in IBD, 18 CHOS treatment appeared to have no obvious effect on LPS-induced IL-8 production of IECs in this study.…”

Secondary metabolites from endophytic fungus from Lippia sidoides Cham.

“…This substance and other flavonoids are credited with antioxidative and anticarcinogenic activity. Naringenin is a flavonoid of the flavanone subclass, found mainly in citrus fruits (Dou et al, 2013), with a beneficial antioxidative and neuroprotective effect (Raza et al, 2013). Among these, the flavonoids catechin and quercetin were also found in plant extracts.…”

Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway

“…Mice were monitored daily for body weight, diarrhea, and bloody stool. Bloody diarrhea event was assessed as described before (3,4). Following measurement of the colon length, the distal colon was taken and fixed in 10% (wt/vol) buffered formalin for H&E staining.…”

“…Lubbad et al (23) have reported that amelioration of TNBS-induce colitis by curcumin is mediated through TLR4-linked NF-B inhibition. We recently demonstrated that naringenin ameliorates DSS-induced colitis via transecting TLR4/NF-B signaling cascades (4). In addition, TLR4 is indicated to be linked with MAPK pathway in IBD.…”