Licochalcone A Potently Inhibits Tumor Necrosis Factor α-Induced Nuclear Factor-κB Activation through the Direct Inhibition of IκB Kinase Complex Activation
- 10 July 2009
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Molecular Pharmacology
- Vol. 76 (4), 745-753
- https://doi.org/10.1124/mol.109.057448
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.Keywords
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