Ent-pimara-8(14), 15-dien-19-oic acid isolated from the roots of Aralia cordata inhibits induction of inflammatory mediators by blocking NF-kappaB activation and mitogen-activated protein kinase pathways

• Published in: European journal of pharmacology 2008-12, Vol.601 (1-3), p.179-185
• Main Authors: Kang, Ok-Hwa, Chae, Hee-Sung, Choi, Jang-Gi, Oh, Yoo-Chang, Lee, Young-Seob, Kim, Jong-Hak, Seung, Man-Jun, Jang, Hye-Jin, Bae, Ki-Hwan, Lee, John-Hwa, Shin, Dong-Won, Kwon, Dong Yeul
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Aralia - chemistry; Cell Line; Cyclooxygenase 2 - drug effects; Cyclooxygenase 2 - metabolism; Diterpenes - isolation & purification; Diterpenes - pharmacology; Gene Expression Regulation - drug effects; I-kappa B Proteins - drug effects; I-kappa B Proteins - metabolism; Inflammation Mediators - metabolism; Interleukin-6 - metabolism; Macrophages - drug effects; Macrophages - metabolism; Medicine, East Asian Traditional; Mice; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - drug effects; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - drug effects; Nitric Oxide Synthase Type II - metabolism; Phosphorylation - drug effects
• ISSN: 1879-0712
• DOI: 10.1016/j.ejphar.2008.10.012

Macrophages play central roles in the innate immune system. The roots of Aralia cordata are widely used in Oriental medicine as a remedy for arthritis. During our program to screen medicinal plants for potential anti-inflammatory compounds, ent-pimara-8(14), 15-dien-19-oic acid (pimaradienoic acid; PA) was isolated from the roots of A. cordata. We examined the effect of PA on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. PA was found to significantly inhibit the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and interleukin-6 (IL-6), as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-6. Furthermore, we examined whether mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) signaling pathways are involved in LPS-induced RAW 264.7 cells. We found that a p38 inhibitor (SB203580) and an ERK 1/2 inhibitor (PD98059) significantly affected LPS-induced IL-6 production. In contrast, a JNK 1/2 inhibitor (SP600125) and PI3K inhibitor (wortmannin or LY294002) did not block the induction of IL-6 production by LPS. The LPS-induced phosphorylation of p38 MAPK and extracellular signal-regulated kinase 1/2 (ERK1/2) was inhibited by PA, but not the phosphorylation of JNK 1/2 and AKT (Ser473). Moreover, PA suppressed I kappaB alpha degradation, NF-kappaB activation and luciferase activity. These results suggest that PA isolated from A. cordata has a potential regulatory effect on inflammatory iNOS, COX-2 and IL-6 expression through blockade of the phosphorylation of MAPKs following I kappaB alpha degradation and NF-kappaB activation.