Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB 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(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), 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-alpha, IL-1beta, 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-kappaB (NF-kappaB), and this was associated with the abrogation of inhibitory kappa B-alpha (IkappaB-alpha) 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-alpha, IL-1beta, and IL-6 inhibition via the downregulation of NF-kappaB activation in RAW 264.7 macrophage cells.
Won
Jong-Heon
JH
College of Pharmacy, Kyung-Hee University, Hoegi-Dong, Seoul, Republic of Korea.
Shin
Ji-Sun
JS
Park
Hee-Juhn
HJ
Jung
Hyun-Ju
HJ
Koh
Duck-Jae
DJ
Jo
Baek-Geon
BG
Lee
Jin-Yong
JY
Yun
Kijoo
K
Lee
Kyung-Tae
KT
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D028041:Centella / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C093443:madecassoside; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C001669:madecassic acid