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 Journal of Natural Medicines Pub Date : 2024-04-02 DOI:10.1007/s11418-024-01798-y

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

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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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

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.