earticle

영어

(-)-α-bisabolol is a sesquiterpene alcohol found in the oils of chamomile and other plants. (-)-α-bisabolol has been widely used in dermatological and cosmetic formulations as an anti-inflammatory agent. But so far there were no studies that show the inhibitory mechanism of (-)-α-bisabolol in inflammation-associated gene expression. Therefore, this study was designed to investigate the anti-inflammatory effect of (-)-α-bisabolol and its mechanisms of action. Among many pro-inflammatory mediators, we found that (-)-α-bisabolol inhibited LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW264.7 cells. In addition, in iNOS and COX-2 promoter luciferase assays, (-)-α-bisabolol reduced LPS-induced activation of iNOS and COX-2 promoters. Protein levels of iNOS and COX-2 were also reduced by (-)-α-bisabolol in a concentration-dependent manner. These results suggest that (-)-α-bisabolol exerts anti-inflammatory effects by downregulating expression of iNOS and COX-2.In order to elucidate inhibitory mechanisms of (-)-α-bisabolol on expression of iNOS and COX-2, we investigated effects of (-)-α-bisabolol on LPS-induced activation of AP-1 and NF-kB elements which exist in the promoter of iNOS and COX-2 genes. LPS-induced activation of AP-1 and NF-kB promoters was significantly reduced by (-)-α-bisabolol, suggesting that AP-1 and NF-kB promoters are involved in (-)-α-bisabolol effects. To further confirm this, ELISA for phospho-IkBa and Western blot for phospho-p42/44mapk, phospho-p38mapk, and phospho-JNK were performed. (-)-α-bisabolol reduced LPS-induced phosphorylation of IkBa. In addition, while LPS-induced phosphorylation of p42/44mapk and p38mapk was attenuated by (-)-α-bisabolol, significant change in the level of phosphorylated JNK was not observed. Collectively, our results indicate that (-)-α-bisabolol exerts anti-inflammatory effects by downregulating expression of iNOS and COX-2 genes through the inhibition of NF-kB and AP-1 (p42/44mapk and p38mapk) signaling pathway and suggest that (-)-α-bisabolol may be introduced for the treatment of inflammatory diseases.