title: Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-kappaB p65 phosphorylation at serine 276.
abstract: Licorice root, Glycyrrhiza inflata, has been used as a traditional medicine for the treatment of bronchial asthma and inflammation; however, the mechanism of its anti-inflammatory activity has not been clarified. Here, we investigated the effect of Licochalcone A, a major component of G. inflata, on the LPS signaling pathway. We found that Licochalcone A remarkably inhibited LPS-induced NO production, and TNFalpha expression and MCP-1 expression in both RAW264.7 cells and primary macrophages. Furthermore, when injected with Licochalcone A prior to injection of LPS, the serum level of TNFalpha and MCP-1 in C57BL/6 mice was clearly decreased, indicating that Licochalcone A has a potent anti-inflammatory effect both in vitro and in vivo. Strikingly, Licochalcone A significantly inhibited LPS-induced NF-kappaB transcriptional activation; however, it had no effect on not only the phosphorylation and degradation of IkappaBalpha but also nuclear translocation and DNA binding activity of NF-kappaB p65. Interestingly, Licochalcone A markedly inhibited the phosphorylation of p65 at serine 276. As a result, it reduced NF-kappaB transactivation by preventing the interaction of p65 with p300. Taken together, Licochalcone A might contribute to the potent anti-inflammatory effect of G. inflata through the unique mechanism of NF-kappaB inhibition.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furusawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.forename: Kenji
authors.initials: K
authors.lastname: Tago
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Mashino
authors.forename: Hideo
authors.initials: H
authors.lastname: Inoue
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism; D006035:Glycyrrhiza / Q000737:chemistry; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D047188:Chalcones; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D012694:Serine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C070840:licochalcone A