Anti-inflammatory effects of madecassic acid via the suppression of NF-κB pathway in LPS-induced RAW 264.7 macrophage cells

We have investigated the anti-inflammatory effects of madecassic acid and madecassoside isolated from Centella asiatica (Umbelliferae) on lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Both madecassic acid and madecassoside inhibited the production of nitric oxide (NO), prostaglandin E(PGE, tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and IL-6. However, madecassic acid more potently suppressed these inflammatory mediators than did madecassoside. Consistent with these observations, madecassic acid inhibited the LPS-induced expression of iNOS and COX-2 at the protein level and of iNOS, COX-2, TNF-, IL-1, and IL-6 at the mRNA level in RAW 264.7 macrophage cells, as determined by Western blotting and RTPCR, respectively. Furthermore, madecassic acid suppressed the LPS-induced activation of nuclear factor-B (NF-B), and this was associated with the abrogation of inhibitory kappa B- (IB-) degradation and with the subsequent blocking of p65 protein translocation to the nucleus. These results suggest that the anti-inflammatory properties of madecassic acid are caused by iNOS, COX-2, TNF-, IL-1, and IL-6 inhibition via the downregulation of NF-B activation in RAW 264.7 macrophage cells.