Peperomins as anti-inflammatory agents that inhibit the NF-kappaB signaling pathway

Chieko Tsutsui; Yuriko Yamada; Masayoshi Ando; Daisuke Toyama; Jian-Lin Wu; Liyan Wang; Shigeru Taketani; Takao Kataoka

doi:10.1016/j.bmcl.2009.06.029

Peperomins as anti-inflammatory agents that inhibit the NF-kappaB signaling pathway

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4084-7. doi: 10.1016/j.bmcl.2009.06.029. Epub 2009 Jun 13.

Authors

Chieko Tsutsui¹, Yuriko Yamada, Masayoshi Ando, Daisuke Toyama, Jian-Lin Wu, Liyan Wang, Shigeru Taketani, Takao Kataoka

Affiliation

¹ Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.

PMID: 19559609
DOI: 10.1016/j.bmcl.2009.06.029

Abstract

The transcription factor nuclear factor kappaB (NF-kappaB) induces the expression of various inflammatory genes. In the common NF-kappaB signaling pathway, peperomin E and 2,6-didehydropeperomin B inhibited IkappaB degradation upon stimulation with TNF-alpha or interleukin-1. Consistent with these results, peperomin E and 2,6-didehydropeperomin B blocked the TNF-alpha-induced activation of IkappaB kinase, while they had no direct effect on the IkappaB kinase activity. Our present results clearly demonstrate that peperomins inhibit the NF-kappaB signaling pathway by blocking IkappaB kinase activation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents / chemical synthesis*
Anti-Inflammatory Agents / pharmacology*
Benzodioxoles / chemical synthesis*
Benzodioxoles / pharmacology
Cell Line, Tumor
Chemistry, Pharmaceutical / methods
Drug Design
Gene Expression Regulation
Humans
Inflammation / drug therapy*
Interleukin-1 / metabolism
Models, Chemical
NF-kappa B / metabolism*
Phosphorylation
Signal Transduction
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / metabolism

Substances

2,6-didehydropeperomin B
Anti-Inflammatory Agents
Benzodioxoles
Interleukin-1
NF-kappa B
Tumor Necrosis Factor-alpha
peperomin E