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

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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.

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Acknowledgements

This work was partly supported by JSPS KAKENHI (JP 19K07152 and JP22K06671 to MH), Japan.

Funding

This work was partly supported by JSPS KAKENHI (JP 19K07152 and JP22K06671 to MH), Japan.

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Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo, 142-8501, Japan

    Yuki Nakajima, Naohide Tsuboi, Kumiko Katori, Maigunuer Waili, Alfarius Eko Nugroho, Kazunori Takahashi, Hitomi Nishino, Yusuke Hirasawa, Toshio Kaneda & Hiroshi Morita

  2. National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan

    Yoko Kawasaki & Yukihiro Goda

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  1. Yuki Nakajima
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Contributions

Yuki Nakajima, Naohide Tsuboi, Kumiko Katori, Maigunuer Waili, Yusuke Hirasawa, Toshio Kaneda, and Hiroshi Morita conceived and designed the experiments; Alfarius Eko Nugroho, Hitomi Nishino, Kazunori Takahashi, Yoko Kawasaki, and Yukihiro Goda prepared mollugin and oxomollugin; Yuki Nakajima and Toshio Kaneda and Hiroshi Morita wrote the paper.

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Correspondence to Toshio Kaneda or Hiroshi Morita.

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Nakajima, Y., Tsuboi, N., Katori, K. et al. Oxomollugin, an oxidized substance in mollugin, inhibited LPS-induced NF-κB activation via the suppressive effects on essential activation factors of TLR4 signaling. J Nat Med 78, 568–575 (2024). https://doi.org/10.1007/s11418-024-01798-y

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