The fixed structure of Licochalcone A by α, β-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-κB activation

Megumi Funakoshi-Tago, Kei Nakamura, Rina Tsuruya, Masashi Hatanaka, Tadahiko Mashino, Yoshiko Sonoda, Tadashi Kasahara

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Glycyrrhiza inflata has been used as a traditional medicine with anti-inflammatory activity. Previously, we reported that a major component, Licochalcone A, potently inhibited TNFα-induced NF-κB activation by inhibiting IKKβ activation. In this study, we investigated whether the fixed structure of Licochalcone A by α, β-unsaturated ketone is required for its inhibitory effect of NF-κB activation. Interestingly, reduced Licochalcone A, which lacks a double bond, failed to inhibit TNFα-induced NF-κB activation. Whereas Licochalcone A potently inhibited TNFα-induced IKK activation, IκBα degradation, nuclear localization of NF-κB and its DNA binding activity, no inhibitory effect was observed by reduced Licochalcone A. In addition, TNFα-induced expression of inflammatory cytokines, CCL2/MCP-1 and CXCL1/KC, was clearly inhibited by Licochalcone A but not reduced Licochalcone A. As a result, culture media pretreated with Licochalcone A but not reduced Licochalcone A following TNFα stimulation significantly inhibited the chemotactic activity of neutrophils. Furthermore, acute carrageenan-induced paw edema in mice was markedly inhibited by administration of Licochalcone A but not reduced Licochalcone A. Taken together, it is suggested that Licochalcone A is a promising anti-inflammatory drug in vivo and its fixed structure is critical for anti-inflammatory activity.

Original languageEnglish
Pages (from-to)562-571
Number of pages10
JournalInternational Immunopharmacology
Volume10
Issue number5
DOIs
Publication statusPublished - 2010 May 1

Keywords

  • Glycyrrhiza inflata
  • Licochalcone A
  • NF-κB
  • Reduced Licochalcone A
  • TNFα

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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