RESUMO
This study was conducted to demonstrate the inhibitory effect of saucerneol G (SG), a new lignan, isolated from the aerial part of Saururus chinensis (Saururaceae) on lipopolysaccharide (LPS)-stimulated matrix metalloproteinase-9 (MMP)-9 inductions in RAW 264.7 cells. Aimed at evaluating the mechanism of action by which SG inhibits the LPS-mediated induction of MMP-9, the effects of SG on nuclear factor-κB (NF-κB) DNA binding activity, NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation, degradation and p65 nuclear translocation were assessed. SG profoundly suppressed the DNA binding activity and the reporter gene activity as well as translocation of NF-κB p65 subunit. Furthermore, SG also dose dependently inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). These findings suggest that SG may inhibit LPS-stimulated MMP-9 induction by blocking NF-κB and MAPKs activation.
Assuntos
Anti-Inflamatórios/farmacologia , Lignanas/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/farmacologia , Saururaceae/química , Fator de Transcrição RelA/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , DNA/metabolismo , Relação Dose-Resposta a Droga , Genes Reporter/fisiologia , Lignanas/isolamento & purificação , Lipopolissacarídeos , Camundongos , Componentes Aéreos da Planta , Extratos Vegetais/química , Raízes de PlantasRESUMO
Meso-dihydroguaiaretic acid (MDGA) is a medicinal herbal product isolated from the aerial parts of Saururus chinensis that inhibits the cyclooxygenase-2 (COX-2)-dependent phase of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) (IC(50) 9.8 microM). However, this compound did not inhibit COX-2 protein expression in BMMC at concentrations up to 30 microM, indicating that MDGA directly inhibits COX-2 activity. In addition, this compound consistently inhibited the production of leukotriene C(4) (IC(50) 1.3 microM). These results demonstrate that MDGA inhibits both COX-2 and 5-lipoxygenase. Furthermore, this compound strongly inhibited the degranulation reaction in BMMC (IC(50) 11.4 microM). Therefore, this compound might provide a basis for novel anti-inflammatory drug development.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Guaiacol/análogos & derivados , Lignanas/farmacologia , Inibidores de Lipoxigenase , Mastócitos/efeitos dos fármacos , Saururaceae , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Ácido Araquidônico/metabolismo , Células da Medula Óssea/enzimologia , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Guaiacol/isolamento & purificação , Guaiacol/farmacologia , Lignanas/isolamento & purificação , Masculino , Mastócitos/enzimologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
5-Methoxy-8-(2-hydroxy-3-buthoxy-3-methylbutyloxy)-psoralen (MP) is a medicinal herbal product isolated from Angelica dahurica that inhibits the cyclooxygenase-2 (COX-2)-dependent phase of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (IC(50), 23.5 microM). Western blotting with specific anti-COX-2 antibodies showed that the decrease in PGD(2) production was accompanied by a decrease in COX-2 protein levels. In addition, this compound consistently inhibited the production of leukotriene C(4) in a dose dependent manner, (IC(50), 2.5 microM). These results demonstrate that MP inhibits both cyclooxygenase-2 and 5-lipoxygenase activity. Furthermore, this compound also inhibited the degranulation reaction (IC(50), 4.1 microM). Therefore, this compound might provide a basis for novel anti-inflammatory drug development.
