Curcumin attenuates inflammation through inhibition of TLR-4 receptor in experimental colitis

Abstract

Curcumin, an active ingredient of Curcumin longa mediates its anti-inflammatory effects through inhibition of NFkB. Several pathways including toll-like receptors (TLR) induce NFkB leading to inflammation. In this study, we investigated the effects of curcumin on the expression of TLR-4 and MyD88, the upstream signaling pathway in experimental colitis induced in the Sprague-Dawley male rats by intra-rectal administration of trinitrobenzenesulfonic acid (TNBS). The animals which received TNBS were divided into two groups: Group 1, received aqueous suspension of curcumin (100 mg/Kg body weight) 2 h prior to inducing colitis, and the treatment was repeated every day for 5 days, and Group 2 and non-colitis (Group 3) animals received phosphate buffered saline (PBS) in a similar fashion. Non-colitis animals (Group 4) received curcumin and served as controls. Animals were sacrificed on day 5 post-TNBS by cervical dislocation, colon was taken out, and cleaned with PBS. Levels of TLR-4, MyD88, and NFkB proteins were measured using ECL Western blot analysis, and TLR-4 mRNA by a competitive RT-PCR method. Colitis was confirmed histologically by measuring myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels in the colonic tissues. TNBS-induced increase in the level of MPO activity and MDA concentrations was reversed by curcumin treatment, whereas the same dose of curcumin did not affect their levels in the non-colitis animals. Increases in the levels of TLR-4, MyD88, and NFkB proteins in inflamed tissue were also suppressed significantly by curcumin treatment. The level of TLR-4 mRNA remained unchanged in the colitis animals. These findings demonstrate that signaling pathway of curcumin-induced inhibition of inflammation involves TLR-4 and MyD88, and therefore may serve as an important therapeutic target in IBD.

Curcumin: an orally bioavailable blocker of TNF and other pro‐inflammatory biomarkers

“…Ninthly, curcumin combined with resveratrol and simvastatin decreases acute small intestinal inflammation in mice by down-regulating the Th1-type immune response (Bereswill et al, 2010). Tenthly, curcumin suppresses TNBS-induced colonic inflammation in mice by down-regulation of NFkB, TLR4 and MyD88 (Lubbad et al, 2009a). Eleventhly, curcumin has been shown to inhibit colitis by inducing the production of tolerogenic dendritic cells that promote differentiation of T-cells into Treg, which include CD4 + CD25 + Foxp3 + Treg and IL-10-producing Tr1 cells, and by producing TGF-b (Cong et al, 2009).…”

“…• Attenuated the TNBS-induced colitis in rats through suppression of expression in TLR-4, MyD88 and NF-kB proteins in inflamed tissue (Lubbad et al, 2009a). …”

Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways

“…Evidence is mounting for the argument that TLR4 plays an important role in the progression of atherosclerosis: one study demonstrated that TLR4 is markedly overexpression in human atherosclerotic plaques, while in other experiments involving TLR4 knockouts, scientists were able to reduce area and vulnerability of atherosclerotic plaques [11,12] . Furthermore, Cur has been found to attenuate inflammation via inhibition of the TLR4 receptor in experimental colitis [13] . The NF-κB signaling pathway, being downstream of TLR4-mediated signaling, plays a critical role in amplifying inflammatory responses by upregulating the expression of various proinflammatory cytokines genes [14] .…”

The *1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis

“…Lipopolysaccharide signaling is mainly mediated through the cell surface TLRs, which have been shown to be extremely important to gut homeostasis during host-microbial interactions (20,21). TLR-4 plays a significant role in gut innate immunity, protection and is involved in human inflammatory bowel diseases (IBDs), including UC (22,23). Cantó et al reported that a marked increase of TNF-α response to TLR2 ligands correlated with a higher TLR2 expression in Crohn's disease and UC patients, indicating that an abnormal mechanism may provide an excess of inflammatory mediators during the active phases of IBDs (24).…”