Licochalcone A potently inhibits tumor necrosis factor α-induced nuclear factor-κB activation through the direct inhibition of IκB kinase complex activation

Megumi Tago, Saeko Tanabe, Kenji Tago, Hiroshi Itoh, Tadahiko Mashino, Yoshiko Sonoda, Tadashi Kasahara

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Abstract

Glycyrrhiza inflata has been used as a traditional medicine with anti-inflammatory activity; however, its mechanism has not been fully understood. Licochalcone A is a major and biogenetically characteristic chalcone isolated from G. inflata. Here, we found that licochalcone A strongly inhibited tumor necrosis (TNF)-α-induced nuclear localization, DNA binding activity, and the transcriptional activity of nuclear factor-κB (NF-κB). Whereas licochalcone A had no effect on the recruitment of receptor-interacting protein 1 and IκB kinase β (IKKβ) to TNF receptor I by TNF-α, it significantly inhibited TNF-α-induced IκB kinase complex (IKK) activation and inhibitor of nuclear factor-κB degradation. It is interesting that we found that the cysteine residue at position 179 of IKKβ is essential for licochalcone A-induced IKK inhibition, because licochalcone A failed to affect the kinase activity of the IKKβ (C179A) mutant. In contrast, a structurally related compound, echinatin, failed to inhibit TNF-α-induced IKK activation and NF-κB activation, suggesting that the 1,1-dimethy-2-propenyl group in licochalcone A is important for the inhibition of NF-κB. In addition, TNF-α-induced expression of inflammatory cytokines CCL2/monocyte chemotactic protein-1and CXCL1/KC was clearly inhibited by licochalcone A but not echinatin. Taken together, licochalcone A might contribute to the potent anti-inflammatory effect of G. inflata through the inhibition of IKK activation.

Original languageEnglish
Pages (from-to)745-753
Number of pages9
JournalMolecular Pharmacology
Volume76
Issue number4
DOIs
Publication statusPublished - 2009 Oct

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Phosphotransferases
Tumor Necrosis Factor-alpha
Monocyte Chemoattractant Proteins
Anti-Inflammatory Agents
I-kappa B Kinase
Receptor-Interacting Protein Serine-Threonine Kinases
Glycyrrhiza
Chalcone
licochalcone A
Tumor Necrosis Factor Receptors
Traditional Medicine
Cysteine
Necrosis
Cytokines
DNA
Neoplasms

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

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Licochalcone A potently inhibits tumor necrosis factor α-induced nuclear factor-κB activation through the direct inhibition of IκB kinase complex activation. / Tago, Megumi; Tanabe, Saeko; Tago, Kenji; Itoh, Hiroshi; Mashino, Tadahiko; Sonoda, Yoshiko; Kasahara, Tadashi.

In: Molecular Pharmacology, Vol. 76, No. 4, 10.2009, p. 745-753.

Research output: Contribution to journalArticle

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