title: 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.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University, Dongdaemun-ku, Hoegi-Dong, Seoul 130-701, South Korea.
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Yun
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Jong-Bin
authors.initials: JB
authors.lastname: Kim
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Seo-Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Hee-Juhn
authors.initials: HJ
authors.lastname: Park
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Jung
authors.forename: Young-Wuk
authors.initials: YW
authors.lastname: Cho
authors.forename: Kijoo
authors.initials: K
authors.lastname: Yun
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D051550:I-kappa B Kinase / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D053978:Pentacyclic Triterpenes; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D009569:Nitric Oxide; C017032:asiatic acid; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019908:Proto-Oncogene Proteins c-raf; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; D015232:Dinoprostone; C004446:asiaticoside