title: Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-kappaB p65 in LPS signaling pathway.
abstract: Licorice root has been used as a traditional medicine for the treatment of gastric ulcer, bronchial asthma and inflammation. Licochalcone A is a major component of Xinjiang licorice, Glycyrrhiza inflata. Previously we showed that Licochalcone A significantly inhibited LPS-induced NF-kappaB transcriptional activation by abrogating the phosphorylation of NF-kappaB p65 at serine 276. Glycyrrhiza inflata contains not only Licochalcone A but also Licochalcone B, Licochalcone C, Licochalcone D, Echinatin and Isoliquiritigenin, harboring the common structure of chalcones. No chalcones had any effect on LPS-induced IkappaB degradation, nuclear translocation and DNA binding activity of NF-kappaB p65; however, we observed that Licochalcone B and Licochalcone D significantly inhibited LPS-induced phosphorylation at serine 276 and transcriptional activation of NF-kappaB, the same as Licochalcone A. Interestingly, we also found that Licochalcone A, Licochalcone B and Licochalcone D effectively inhibited LPS-induced activation of PKA, which is required for the phosphorylation of NF-kappaB p65 at serine 276. Consequently, Licochalcone B and Licochalcone D significantly reduced the LPS-induced production of NO, TNFalpha and MCP-1. On the other hand, Licochalcone C, Echinatin and Isoliquitigenin failed to inhibit LPS-induced NF-kappaB activation. These findings suggest that the anti-inflammatory effect of Glycyrrhiza inflata is ascribable to the potent inhibition of NF-kappaB by Licochalcone A, Licochalcone B and Licochalcone D.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacology, Keio University, Tokyo, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furusawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Mashino
authors.forename: Kenji
authors.initials: K
authors.lastname: Tago
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; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006035:Glycyrrhiza / Q000737:chemistry; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047188:Chalcones; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D011763:Pyrrolizidine Alkaloids; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C541529:licochalcone D; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; C541528:licochalcone B; C070840:licochalcone A; C018336:indicine