Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1947513 | Biochimica et Biophysica Acta (BBA) - General Subjects | 2014 | 9 Pages |
•Kolaviron blocks IκBα, MAPKs, and AP-1 signalling.•Kolaviron blocks Akt phosphorylation.•Kolaviron did not block CREB activation.•Kolaviron blocks LPS induced secretion of IL-6 but not that of TNF-α.
BackgroundKolaviron (Kol-v), an important component of Garcinia kola seed has a variety of biologic activities, including anti-inflammatory properties.MethodsWe tested the ability of Kol-v to block signalling pathways implicated in lipopolysaccharide (LPS)-induced inflammatory gene expression in RAW 264.7 macrophage cell line.ResultsWhen macrophages pre-treated with Kol-v (15 and 25 μM) were activated with LPS, phosphorylation of p38 and p-c-JUN but not IκBα degradation and phosphorylation of NF-κB (p65), ERK1/2, and IκBα were blocked. Furthermore, Kol-v suppressed LPS-induced increase in the expression of IL-18 gene and LPS-induced decrease in the mRNA expression of IP-10 but it had no effect on the LPS-induced decrease in the gene expression levels of IL-1α, IL-33, IL-1β, and IFNβ1-1. When macrophages pre-treated with Kol-v (50 and 100 μM) were activated with LPS, phosphorylation of Akt, ERK1/2, IκBα, and NFκB (p65) but not that of CREB was blocked by Kol-v. The protective effect of Kol-v on the LPS-induced phosphorylation of the mitogen activated protein kinase (MAPK) family member JNK was only observed at 100 μM. At all concentrations of Kol-v (0–100 μM) tested in this study, there was no effect of Kol-v on LPS-induced secretion of the pro-inflammatory cytokine TNF-α but a concentration dependent inhibition of Kol-v on IL-6 secretion was observed.ConclusionKol-v interferes with LPS signalling by reducing the activation of several inflammatory transcription factors and that its inhibitory action on IL-6 secretion correlates with inhibition of ERK1/2, p38, Akt, p-c-JUN and JNK signalling pathways.General significanceThe anti-inflammatory potential of Kol-v via inhibition of IL-6 secretion in RAW macrophage was established in this study.
Graphical abstractAnti-inflammatory activity of Garcinia kola extract in LPS-induced RAW 264.7 macrophages.Figure optionsDownload full-size imageDownload high-quality image (192 K)Download as PowerPoint slide