Furuhashi Ikue, Iwata Susumu, Shibata Shoji, Sato Toshitsugu, Inoue Hideo
Pharmacological Research Department, Research Laboratory, Minophagen Pharmaceutical Co. Ltd, 2-2-3, Komatsubara, Zama-shi, Kanagawa 228-0002, Japan.
J Pharm Pharmacol. 2005 Dec;57(12):1661-6. doi: 10.1211/jpp.57.12.0017.
Licochalcone A, a novel flavonoid isolated from the root of Glycyrrhiza inflata, has been reported to exhibit anti-inflammatory activity in animal models. In this study, we examined the effect of licochalcone A on the production of chemical mediators such as prostaglandin (PG)E2 and cytokines by interleukin (IL)-1beta in human skin fibroblasts. Licochalcone A (IC50 15.0 nM) inhibited PGE2 production, but not IL-6 and IL-8 production, in response to IL-1beta. NS-398 (IC50 1.6 nM), a COX-2 selective inhibitor, also suppressed the PGE2 production. Furthermore, licochalcone A and NS-398 suppressed PGF(2alpha) production by IL-1beta. However, licochalcone A (1 microM) had no effect on increased levels of cyclooxygenase (COX)-2 mRNA and protein in cells. Dexamethasone (100 nM) not only inhibited PGE2, PGF(2alpha), IL-6 and IL-8 production but also strongly suppressed the expression of COX-2 mRNA and protein. Licochalcone A had no effect on COX-1-dependent PGE2 production, whereas indometacin (100 nM), a dual inhibitor of COX-1 and COX-2, was very effective. These results suggest that licochalcone A induces an anti-inflammatory effect through the inhibition of COX-2-dependent PGE2 production. Furthermore, it appears that the inhibitory effect of licochalcone A on PGE2 production in response to IL-1beta is quite different from that of the steroid.
光甘草定A是从胀果甘草根中分离出的一种新型黄酮类化合物，据报道在动物模型中具有抗炎活性。在本研究中，我们检测了光甘草定A对人皮肤成纤维细胞中白细胞介素（IL）-1β诱导的前列腺素（PG）E2等化学介质及细胞因子产生的影响。光甘草定A（半数抑制浓度[IC50]为15.0 nM）可抑制IL-1β诱导的PGE2产生，但不影响IL-6和IL-8的产生。COX-2选择性抑制剂NS-398（IC50为1.6 nM）也可抑制PGE2产生。此外，光甘草定A和NS-398可抑制IL-1β诱导的PGF2α产生。然而，光甘草定A（1 μM）对细胞中环氧化酶（COX）-2 mRNA和蛋白水平的升高没有影响。地塞米松（100 nM）不仅可抑制PGE2、PGF2α、IL-6和IL-8的产生，还可强烈抑制COX-2 mRNA和蛋白的表达。光甘草定A对COX-1依赖性PGE2的产生没有影响，而COX-1和COX-2的双重抑制剂吲哚美辛（100 nM）则非常有效。这些结果表明，光甘草定A通过抑制COX-2依赖性PGE2的产生发挥抗炎作用。此外，光甘草定A对IL-1β诱导的PGE2产生的抑制作用似乎与类固醇的抑制作用有很大不同。
