RESUMEN
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.
Asunto(s)
Antiinflamatorios/farmacología , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Extractos Vegetales/farmacología , Rosaceae/química , Animales , Línea Celular , Inhibidores de la Ciclooxigenasa 2/farmacología , Dinoprostona/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas I-kappa B/antagonistas & inhibidores , Interleucina-6/antagonistas & inhibidores , Macrófagos/efectos de los fármacos , Ratones , Inhibidor NF-kappaB alfa , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Fosforilación , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Schisandra fructus has been used for treatment of cough and thirst in Korea. However, its therapeutic mechanisms remain largely unclear. To investigate the biological effect of Schisandra fructus water extract (SFWE), we examined the effect of SFWE on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced pro-inflammatory cytokine secretion in the human mast cell line HMC-1. HMC-1 cells were stimulated with PMA plus A23187 in the presence or absence of SFWE. Tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) productions were measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. Inhibitory IkappaB/nuclear factor-kappaB (NF-kappaB) expression was assessed by western blot. SFWE suppressed PMA plus A23187-induced TNF-alpha, IL-6, and GM-CSF production in dose-dependent manners. Furthermore, SFWE inhibited IkappaB degradation and NF-kappaB nuclear translocation. These results suggest that SFWE inhibits the secretion of pro-inflammatory cytokines in HMC-1 cells through blockade of IkappaB degradation and NF-kappaB activation. Taken together, these findings may help elucidate the mechanism of action of this medicine in the modulation of mast cell activation in inflammatory conditions.
Asunto(s)
Citocinas/metabolismo , Mastocitos/metabolismo , Extractos Vegetales/farmacología , Schisandra/química , Calcimicina/farmacología , Línea Celular Tumoral , Medios de Cultivo Condicionados/química , Expresión Génica/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leucemia de Mastocitos , Mastocitos/efectos de los fármacos , FN-kappa B/metabolismo , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Acetato de Tetradecanoilforbol/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , AguaRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for a number of infections in humans that are difficult to treat, and as a result, is a substantial contributor to morbidity and mortality. In the present study, in search of natural products capable of inhibiting this multidrug-resistant bacterium, we investigated the antimicrobial activity of rhein isolated from Rheum palmatum L. (Polygonaceae) against 16 different strains of the bacterium. New antimicrobial activity was found using the paper disc diffusion method [minimal inhibitory concentrations (MICs)], MTT test and checkerboard dilution test. Against the 16 strains, the disc diffusion test was in the range of 20-29 mm and the MICs of rhein were in the range of 7.8-31.25 µg/ml. From these results we performed the checkerboard test to determine the synergism of rhein in combination with ampicillin (AM) or oxacillin (OX) against all strains. The combined activity of rhein and the two antimicrobial agents (AM and OX) against all strains resulted in a fractional inhibitory concentration index ranging from 0.28-1 and from 0.18-1, respectively. The effect of rhein with AM and OX was found to be synergistic or partially synergistic. We found that rhein reduced the MICs of AM and OX. Rhein in combination with AM or OX could lead to the development of new combinations of antibiotics against MRSA infection.