International immunopharmacology
-
Int. Immunopharmacol. · Apr 2010
Anti-inflammatory effect of lucidone in mice via inhibition of NF-kappaB/MAP kinase pathway.
Here, we investigated the anti-inflammatory activity of lucidone, a phytocompound isolated from the fruits of Lindera erythrocarpa Makino, against lipopolysaccharide (LPS)-induced acute systemic inflammation in mice. Male ICR mice were injected intraperitoneally with LPS (5 microg/kg), and the effects of pretreatment with various concentrations of lucidone (50-200 mg/kg) for 12h on the formation of nitric oxide (NO), prostaglandin-E(2) (PGE(2)) and tumor necrosis factor (TNF-alpha) were analyzed. Lucidone inhibited the production of NO, PGE(2) and TNF-alpha production in LPS-induced mice, and also induced mRNA and protein levels of inducible nitric oxide synthase (iNOS), and cyclooxigenase-2 (COX-2). ⋯ Moreover, lucidone decreased the expression and phosphorylation of c-Jun N-terminal kinase (JNK) protein thereby causing the subsequent inhibition of AP-1 activity. Finally, our results indicated that lucidone was able to block mitogen-activated protein kinases activity and its downstream signaling activation of NF-kappaB and AP-1. We thus conclude that lucidone exerts its anti-inflammatory effects in mice by inhibiting the expression of pro-inflammatory factors and their related signaling pathways.
-
Int. Immunopharmacol. · Apr 2010
A phenolic acid phenethyl urea compound inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines in cell culture.
We previously used the Curtius rearrangement to synthesize various phenolic acid phenethyl urea compounds from phenolic acids and demonstrated their beneficial anti-oxidant and anti-cancer effects. Here, we investigated the effects of one of these synthetic compounds, (E)-1-(3,4-dihydroxystyryl)-3-(4-hydroxyphenethyl)urea (DSHP-U), on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression, and cytokine secretion in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. DSHP-U suppressed LPS-induced NO production and iNOS expression at a concentration of 50 microM and inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase. ⋯ Furthermore, DSHP-U decreased the production of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 in LPS-treated macrophages. However, the LPS-stimulated expression of LPS receptors, such as Toll-like receptor 4, myeloid differentiation factor-2, and CD14, was unchanged after DSHP-U treatment at significantly high levels. Our data suggest that DSHP-U blocks NO and inflammatory cytokine production in LPS-stimulated macrophages and that these effects are mainly mediated through the inhibition of the ERK/p38- and NF-kappaB signaling pathways.
-
Int. Immunopharmacol. · Apr 2010
Pharmacological profile of AW-814141, a novel, potent, selective and orally active inhibitor of p38 MAP kinase.
The p38 mitogen activated protein kinase (MAPK) is a key signaling molecule that plays a crucial role in the progression of various inflammatory diseases such as rheumatoid arthritis (RA), asthma and chronic obstructive pulmonary disease. The objective of the present study was to evaluate the anti-inflammatory activity of a p38 MAPK inhibitor, AW-814141. AW-814141 inhibited enzymatic activity of recombinant p38-alpha and beta isoforms with IC(50) value of 100nM and 158nM, respectively. ⋯ In a carrageenan-induced rat paw edema model and collagen-induced arthritis model (CIA), AW-814141 dose dependently inhibited paw swelling. In different in vivo efficacy models, efficacy of AW-814141 was found to be better as compared to the reference compounds (Vx-745 and BIRB-796). This study demonstrated that AW-814141 is a novel p38 MAPK inhibitor and it displays promising in vitro and in vivo anti-inflammatory activities and can be used for the treatment of rheumatoid arthritis.