Oxomollugin, an oxidized substance in mollugin, inhibited LPS-induced NF-κB activation via the suppressive effects on essential activation factors of TLR4 signaling

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL
Yuki Nakajima, Naohide Tsuboi, Kumiko Katori, Maigunuer Waili, Alfarius Eko Nugroho, Kazunori Takahashi, Hitomi Nishino, Yusuke Hirasawa, Yoko Kawasaki, Yukihiro Goda, Toshio Kaneda, Hiroshi Morita
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Abstract

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.

Graphical Abstract

Abstract Image

Oxomollugin是软骨素中的一种氧化物质,它通过抑制TLR4信号的基本激活因子,抑制LPS诱导的NF-κB激活。
Oxomollugin 是 mollugin 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。在本研究中,我们研究了 Oxomollugin 的抑制活性,重点是 TLR4 信号通路导致的 NF-κB 激活。氧代木糖醇抑制了 LPS 诱导的 TLR4 信号通路初始激活的重要因子 MyD88、IRAK4 和 TRAF6 的结合。此外,氧化木糖醇对 LPS 诱导的 IRAK1、IRAK2 和 TRAF6 的修饰、LPS 诱导的 TRAF6-TAK1/TAB2 的结合以及随后的 IKKα/β 磷酸化均有抑制作用,而 IKKα/β 磷酸化在导致 LPS 诱导的 NF-κB 激活的信号转导中起着关键作用。这些结果一致表明,奥罗莫鲁金通过抑制 TLR4 信号通路中的信号转导来抑制 LPS 诱导的 NF-κB 激活。
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来源期刊
CiteScore
6.90
自引率
3.00%
发文量
79
审稿时长
1.7 months
期刊介绍: The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.
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