TY - JOUR
T1 - Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-κB p65 in LPS signaling pathway
AU - Furusawa, Jun ichi
AU - Funakoshi-Tago, Megumi
AU - Mashino, Tadahiko
AU - Tago, Kenji
AU - Inoue, Hideo
AU - Sonoda, Yoshiko
AU - Kasahara, Tadashi
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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-κB transcriptional activation by abrogating the phosphorylation of NF-κB 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 IκB degradation, nuclear translocation and DNA binding activity of NF-κB p65; however, we observed that Licochalcone B and Licochalcone D significantly inhibited LPS-induced phosphorylation at serine 276 and transcriptional activation of NF-κB, 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-κB p65 at serine 276. Consequently, Licochalcone B and Licochalcone D significantly reduced the LPS-induced production of NO, TNFα and MCP-1. On the other hand, Licochalcone C, Echinatin and Isoliquitigenin failed to inhibit LPS-induced NF-κB activation. These findings suggest that the anti-inflammatory effect of Glycyrrhiza inflata is ascribable to the potent inhibition of NF-κB by Licochalcone A, Licochalcone B and Licochalcone D.
AB - 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-κB transcriptional activation by abrogating the phosphorylation of NF-κB 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 IκB degradation, nuclear translocation and DNA binding activity of NF-κB p65; however, we observed that Licochalcone B and Licochalcone D significantly inhibited LPS-induced phosphorylation at serine 276 and transcriptional activation of NF-κB, 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-κB p65 at serine 276. Consequently, Licochalcone B and Licochalcone D significantly reduced the LPS-induced production of NO, TNFα and MCP-1. On the other hand, Licochalcone C, Echinatin and Isoliquitigenin failed to inhibit LPS-induced NF-κB activation. These findings suggest that the anti-inflammatory effect of Glycyrrhiza inflata is ascribable to the potent inhibition of NF-κB by Licochalcone A, Licochalcone B and Licochalcone D.
KW - Glycyrrhiza inflata
KW - LPS
KW - Licochalcone A
KW - Licochalcone B
KW - Licochalcone D
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=61649115375&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=61649115375&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2009.01.031
DO - 10.1016/j.intimp.2009.01.031
M3 - Article
C2 - 19291859
AN - SCOPUS:61649115375
VL - 9
SP - 499
EP - 507
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 4
ER -