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 E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), 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-α, IL-1β, and IL-6 at the mRNA level in RAW 264.7 macrophage cells, as determined by Western blotting and RT‐PCR, respectively. Furthermore, madecassic acid suppressed the LPS-induced activation of nuclear factor-κB (NF-κB), and this was associated with the abrogation of inhibitory kappa B-α (IκB-α) 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-α, IL-1β, and IL-6 inhibition via the downregulation of NF-κB activation in RAW 264.7 macrophage cells.