Inhibition of LPS-induced NO and PGE2 production by asiatic acid via NF-kappa B inactivation in RAW 264.7 macrophages: possible involvement of the IKK and MAPK pathways.
Int Immunopharmacol. 2008 Mar ;8(3):431-41. Epub 2007 Dec 3. PMID: 18279797
In the present study, we investigated the effect of asiatic acid (the aglycon of asiaticoside) and asiaticoside isolated from the leaves of Centella asiatica (Umbelliferae) on LPS-induced NO and PGE(2) production in RAW 264.7 macrophage cells. Asiatic acid more potently inhibited LPS-induced NO and PGE(2) production than asiaticoside. Consistent with these observations, the protein and mRNA expression levels of inducible iNOS and COX-2 enzymes were inhibited by asiatic acid in a concentration-dependent manner. In addition, asiatic acid dose-dependently reduced the production of IL-6, IL-1 beta and TNF-alpha in LPS-stimulated RAW 264.7 macrophage cells. Furthermore, asiatic acid inhibited the NF-kappaB activation induced by LPS, and this was associated with the abrogation of I kappa B-alpha degradation and with subsequent decreases in nuclear p65 and p50 protein levels. Moreover, the phosphorylations of IKK, p38, ERK1/2, and JNK in LPS-stimulated RAW 264.7 cells were suppressed by asiatic acid in a dose-dependent manner. These results suggest that the anti-inflammatory properties of asiatic acid might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1 beta, and TNF-alpha expressions through the down-regulation of NF-kappaB activation via suppression of IKK and MAP kinase (p38, ERK1/2, and JNK) phosphorylation in RAW 264.7 cells.