Annexin A1 accounts for an anti-inflammatory binding target of sesamin metabolites

Yasuaki Kabe, Daisuke Takemoto, Ayaka Kanai, Miwa Hirai, Yoshiko Ono, Sota Akazawa, Manabu Horikawa, Yoshinori Kitagawa, Hiroshi Handa, Tomohiro Rogi, Hiroshi Shibata, Makoto Suematsu

研究成果: Article

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Sesamin [(7α,7′α,8α,8′α)-3,4:3′,4′-bis(methylenedioxy)-7,9′:7′,9-diepoxylignane] is a major lignan in sesame seeds. Sesamin is converted to the catechol metabolite, SC1 [(7α,7′α,8α,8′α)-3′,4′-methylenedioxy-7,9′:7′,9-diepoxylignane-3,4-diol] with anti-inflammatory effects after oral administration. However, its molecular target remains unknown. Analysis using high-performance affinity nanobeads led to the identification of annexin A1 (ANX A1) as an SC1-binding protein. SC1 was found to bind to the annexin repeat 3 region of ANX A1 with a high-affinity constant (Kd = 2.77 μmol L−1). In U937 cells, SC1 exhibited an anti-inflammatory effect dependent on ANX A1. Furthermore, administration of sesamin or SC1 attenuated carbon tetrachloride-induced liver damage in mice and concurrently suppressed inflammatory responses dependent on ANX A1. The mechanism involved SC1-induced ANX A1 phosphorylation at serine 27 that facilitates extracellular ANX A1 release. Consequently, the ANX A1 released into the extracellular space suppressed the production of tumor necrosis factor α. This study demonstrates that ANX A1 acts as a pivotal target of sesamin metabolites to attenuate inflammatory responses.

元の言語English
記事番号4
ジャーナルnpj Science of Food
4
発行部数1
DOI
出版物ステータスPublished - 2020 12 1

ASJC Scopus subject areas

  • Food Science
  • Public Health, Environmental and Occupational Health

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    Kabe, Y., Takemoto, D., Kanai, A., Hirai, M., Ono, Y., Akazawa, S., Horikawa, M., Kitagawa, Y., Handa, H., Rogi, T., Shibata, H., & Suematsu, M. (2020). Annexin A1 accounts for an anti-inflammatory binding target of sesamin metabolites. npj Science of Food, 4(1), [4]. https://doi.org/10.1038/s41538-020-0064-6