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)-alpha-induced
nuclear localization,
DNA binding activity, and the
transcriptional activity of nuclear factor-kappaB (
NF-kappaB). Whereas licochalcone A had no effect on the recruitment of receptor-interacting protein 1 and
IkappaB kinase beta (IKKbeta) to
TNF receptor I by
TNF-alpha, it significantly inhibited TNF-alpha-induced
IkappaB kinase complex (IKK)
activation and inhibitor of nuclear factor-kappaB degradation. It is interesting that we found that the
cysteine residue at position 179 of IKKbeta is essential for licochalcone A-induced IKK inhibition, because licochalcone A failed to affect the
kinase activity of the IKKbeta (C179A)
mutant. In contrast, a structurally related compound, echinatin, failed to inhibit TNF-alpha-induced IKK
activation and
NF-kappaB activation, suggesting that the 1,1-dimethy-2-propenyl group in licochalcone A is important for the inhibition of
NF-kappaB. In addition, TNF-alpha-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.
