Betulinic acid isolated from Bacopa monniera (L.) Wettst suppresses lipopolysaccharide stimulated interleukin-6 production through modulation of nuclear factor-κB in peripheral blood mononuclear cells

The purpose of this study was to investigate the anti-inflammatory function and mechanism(s) of action of an active component-betulinic acid isolated from Bacopa monniera. Betulinic acid, a pentacyclic triterpenoid markedly suppressed lipopolysaccharide (LPS) induced IL-6 production in blood mononuclear cells both in vivo and in vitro. Betulinic acid also prevented LPS induced nuclear translocation of p65 NF-kappa B in hPBMCs. LPS induced nuclear translocation of NF-kappa B and IL-6 production was also abolished by p38 and ERK MAPK inhibitors PD98059 and SB203580. Addition of each of these inhibitors to cell cultures along with betulinic acid caused significant downregulation of IL-6 production and inhibition of p65 NF-kappa B nuclear translocation. The inhibitory effect of both betulinic acid and the inhibitors was higher than that of cells treated with inhibitors alone. These results suggest that betulinic acid inhibited IL-6 production by preventing p65 NF-kappa B nuclear translocation and there is a possibility that this prevention of p65 nuclear translocation may involve p38 and ERK MAPKs as cross talks occur between MAPK and NF-kappa B pathways. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of betulinic acid. (C) 2010 Elsevier B.V. All rights reserved.