School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo, 142-8501, Japan.
National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan.
J Nat Med. 2024 Jun;78(3):568-575. doi: 10.1007/s11418-024-01798-y. Epub 2024 Apr 2.
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/β 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.
氧化脒醇是脒醇的降解产物，被发现是一种抑制 LPS 诱导的 NF-κB 激活的活性化合物。在这项研究中，我们研究了氧化脒醇的抑制活性，重点关注 TLR4 信号通路，导致 NF-κB 激活。氧化脒醇抑制了 LPS 诱导的 TLR4 信号通路初始激活所必需的关键因素 MyD88、IRAK4 和 TRAF6 的结合。此外，氧化脒醇对 LPS 诱导的 IRAK1、IRAK2 和 TRAF6 的修饰、LPS 诱导的 TRAF6-TAK1/TAB2 结合以及随后的 IKKα/β 磷酸化具有抑制作用，这在导致 LPS 诱导的 NF-κB 激活的信号转导中至关重要。一致的结果表明，氧化脒醇通过抑制 TLR4 信号通路中的信号转导来抑制 LPS 诱导的 NF-κB 激活。本研究中报道的氧化脒醇的活性为作为抗炎化合物的脒醇衍生物的生物学活性提供了更深入的了解。
