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

• Published in: Planta medica Vol. 76; no. 3; pp. 251 - 257
• Main Authors: Won, Jong-Heon, Shin, Ji-Sun, Park, Hee-Juhn, Jung, Hyun-Ju, Koh, Duck-Jae, Jo, Baek-Geon, Lee, Jin-Yong, Yun, Kijoo, Lee, Kyung-Tae
• Format: Journal Article
• Language: English
• Published: Germany 01.02.2010
• Subjects: animal models; Animals; anti-inflammatory activity; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; biochemical pathways; biosynthesis; Centella - chemistry; Centella asiatica; chemical constituents of plants; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Down-Regulation; inflammation; Inflammation Mediators - metabolism; interleukin-1; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; interleukin-6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lipopolysaccharides; macrophages; Macrophages - drug effects; Macrophages - metabolism; madecassic acid; madecassoside; medicinal plants; medicinal properties; Mice; NF-kappa B - genetics; NF-kappa B - metabolism; nitric oxide; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; nuclear factor-kB; plant extracts; Plant Extracts - chemistry; Plant Extracts - pharmacology; prostaglandins; RNA, Messenger - metabolism; Triterpenes - isolation & purification; Triterpenes - pharmacology; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-0029-1186142

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.