Kolaviron, a natural flavonoid from the seeds of Garcinia kola, reduces LPS-induced inflammation in macrophages by combined inhibition of IL-6 secretion, and inflammatory transcription factors, ERK1/2, NF-κB, p38, Akt, p-c-JUN and JNK

Background: Kolaviron (Kol-v), an important component of Garcinia kola seed has a variety of biologic activities, including anti-inflammatory properties. Methods: We 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. Results: When macrophages pre-treated with Kol-v (15 and 25 mu M) were activated with LPS, phosphorylation of p38 and p-c-JUN but not I kappa B alpha degradation and phospholylation of NF-kappa B (p65), ERK1/2, and I kappa B alpha 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-1 alpha, IL-33, IL-1 beta, and IFN beta 1-1. When macrophages pre-treated with Kol-v (50 and 100 mu M) were activated with LPS, phosphorylation of Akt, ERK1/2, I kappa B alpha, and NF kappa B (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 mu M. At all concentrations of Kol-v (0-100 mu M) tested in this study, there was no effect of Kol-v on LPS-induced secretion of the pro-inflammatory cytokine TNF-alpha but a concentration dependent inhibition of Kol-v on IL-6 secretion was observed. Conclusion: Kol-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 significance: The anti-inflammatory potential of Kol-v via inhibition of IL-6 secretion in RAW macrophage was established in this study. (C) 2014 Elsevier B.V. All rights reserved.