Sunny O Abarikwu1. 1. Department of Chemical Sciences, College of Natural Sciences, Redeemer's University, Redemption City, Ogun State, Nigeria. Electronic address: abarikwus@run.edu.ng.
Abstract
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 25μM) 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 100μM) 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 100μM. At all concentrations of Kol-v (0-100μM) 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. 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.
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 25μM) 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 100μM) 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 100μM. At all concentrations of Kol-v (0-100μM) 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. 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.
Authors: Afolabi C Akinmoladun; Bolanle L Akinrinola; M Tolulope Olaleye; Ebenezer O Farombi Journal: Neurochem Res Date: 2015-02-01 Impact factor: 3.996