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.
- TNF, tumor necrosis factor
- MCP, monocyte chemotactic protein
- NF-κB, nuclear factor-κB
- IKK, IκB kinase complex
- IκBα, inhibitor of nuclear factor-κB
- TNFR, tumor necrosis factor receptor
- TRADD, tumor necrosis factor receptor-associated death domain
- RIP, receptor-interacting protein
- TRAF, tumor necrosis factor receptor-associated factor
- CMV, cytomegalovirus
- HEK, human embryonic kidney
- FBS, fetal bovine serum
- PBS, phosphate-buffered saline
- GST, glutathione transferase
- RT-PCR, reverse transcriptase-polymerase chain reaction
- GAPDH, glyceraldehyde-3-phosphate dehydrogenase
- ELISA, enzyme-linked immunosorbent assay
- DMSO, dimethyl sulfoxide
- LPS, lipopolysaccharide.
Footnotes
-
This work was supported in part by Ministry of Education, Culture, Sports, Science and Technology Japan [Grants 16390024, 19790071] and the Hi-Tech Research Center Project for Private Universities in Japan.
-
Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
-
ABBREVIATIONS:
- Received May 1, 2009.
- Accepted July 10, 2009.
- © 2009 The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|