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J Nat Med ; 78(3): 568-575, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38564154

RESUMO

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.


Assuntos
Lipopolissacarídeos , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Camundongos , Humanos , Células RAW 264.7 , Fosforilação/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Lactonas , Resorcinóis , Zearalenona/administração & dosagem
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