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

• Published in: Biochimica et biophysica acta Vol. 1840; no. 7; pp. 2373 - 2381
• Main Author: Abarikwu, Sunny O.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2014
• Subjects: Animals; anti-inflammatory activity; flavonoids; Flavonoids - administration & dosage; Flavonoids - chemistry; Garcinia kola; Garcinia kola - chemistry; gene expression; Gene Expression Regulation - drug effects; genes; IKappaB kinase; IL-6; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - pathology; interleukin-18; interleukin-1alpha; interleukin-1beta; interleukin-6; Interleukin-6 - secretion; Kolaviron; Lipopolysaccharide; lipopolysaccharides; Lipopolysaccharides - toxicity; macrophages; Macrophages - drug effects; Macrophages - pathology; MAPK; messenger RNA; Mice; mitogen-activated protein kinase; NF-kappa B - metabolism; phosphorylation; protective effect; RAW macrophage; secretion; seeds; Seeds - chemistry; signal transduction; Signal Transduction - drug effects; transcription factor NF-kappa B; Transcription Factors - genetics; Transcription Factors - metabolism; tumor necrosis factor-alpha; Lipopolysaccharide; Inflammation; Kolaviron; RAW macrophage; MAPK; IL-6
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2014.03.006

Kolaviron (Kol-v), an important component of Garcinia kola seed has a variety of biologic activities, including anti-inflammatory properties. 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. 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. 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. The anti-inflammatory potential of Kol-v via inhibition of IL-6 secretion in RAW macrophage was established in this study. Anti-inflammatory activity of Garcinia kola extract in LPS-induced RAW 264.7 macrophages. [Display omitted] •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.