RESUMO
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.
Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Aralia/química , Linhagem Celular , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Diterpenos/isolamento & purificação , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas I-kappa B/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Medicina Tradicional do Leste Asiático , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
Mume Fructus (Family Rosaceae) is used as a traditional drug and health food in Asian countries. However, its therapeutic mechanisms and effects on macrophage-mediated inflammation remain unknown. In this study we examined the effect of Mume Fructus water extract (MFWE) on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The investigation focused on whether MFWE inhibited nitric oxide (NO) and prostaglandin (PG) E2 productions, as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-6, nuclear factor-kappaB (NF-kappaB), and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells. We found that MFWE inhibited LPS-induced NO, PGE(2), and IL-6 productions as well as the expressions of iNOS and COX-2. Furthermore, MFWE suppressed the LPS-induced phosphorylations of p38 MAPK and extracellular signal-regulated kinase MAPK, as well as IkappaBalpha degradation and NF-kappaB activation. These results suggest that MFWE has inhibitory effects on LPS-induced PGE2, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage. These inhibitory effects occur through blockades on the phosphorylation of MAPKs following IkappaBalpha degradation and NF-kappaB activation.
Assuntos
Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Extratos Vegetais/farmacologia , Rosaceae/química , Animais , Linhagem Celular , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas I-kappa B/antagonistas & inibidores , Interleucina-6/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Camundongos , Inibidor de NF-kappaB alfa , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Fosforilação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Methanol extract and its fractions (hexane, EtOAc, n-BuOH, and H2O) of Dryopteris crassirhizoma were investigated for antibacterial activity against methicillin-resistant Staphylococcus aureus. The hexane fraction showed a good antibacterial activity against all tested strains.