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 language | English |
|---|---|
| Pages (from-to) | 745-753 |
| Number of pages | 9 |
| Journal | Molecular Pharmacology |
| Volume | 76 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2009 Oct |
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ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Licochalcone A potently inhibits tumor necrosis factor α-induced nuclear factor-κB activation through the direct inhibition of IκB kinase complex activation
AU - Tago, Megumi
AU - Tanabe, Saeko
AU - Tago, Kenji
AU - Itoh, Hiroshi
AU - Mashino, Tadahiko
AU - Sonoda, Yoshiko
AU - Kasahara, Tadashi
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=70349337442&partnerID=8YFLogxK
U2 - 10.1124/mol.109.057448
DO - 10.1124/mol.109.057448
M3 - Article
C2 - 19592502
AN - SCOPUS:70349337442
VL - 76
SP - 745
EP - 753
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 4
ER -