RESUMEN
Oxomollugin is a degraded product of mollugin and was found to be an active compound that inhibits LPS-induced NF-κB activation. In this study, we investigated the inhibitory activity of oxomollugin, focusing on TLR4 signaling pathway, resulting in NF-κB activation. Oxomollugin inhibited the LPS-induced association of essential factors for initial activation of TLR4 signaling, MyD88, IRAK4 and TRAF6. Furthermore, oxomollugin showed suppressive effects on LPS-induced modification of IRAK1, IRAK2 and TRAF6, LPS-induced association of TRAF6-TAK1/TAB2, and followed by IKKα/ß phosphorylation, which critical in signal transduction leading to LPS-induced NF-κB activation. The consistent results suggested that oxomollugin inhibits LPS-induced NF-κB activation via the suppression against signal transduction in TLR4 signaling pathway.The activities of oxomollugin reported in this study provides a deeper understanding on biological activity of mollugin derivatives as anti-inflammatory compounds.
Asunto(s)
Lipopolisacáridos , FN-kappa B , Transducción de Señal , Receptor Toll-Like 4 , Receptor Toll-Like 4/metabolismo , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Ratones , Humanos , Células RAW 264.7 , Fosforilación/efectos de los fármacos , Factor 88 de Diferenciación Mieloide/metabolismo , Lactonas , Resorcinoles , Zearalenona/administración & dosificaciónRESUMEN
Mollugin, a naphthoquinone derivative, was reported to possess various biological activities such as anti-inflammatory and anti-tumor activity. Mollugin isolated from Rubia tinctorum roots inhibited lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 macrophages. However, mollugin synthesized for further investigation of its anti-inflammatory mechanism showed weak activity in addition to unstable assay results. From the result of analysis on a degradation product of mollugin, oxomollugin was found to be the main active substance of mollugin degradation, showing a potent inhibitory activity on NO-production including nuclear factor kappa B signals.