RESUMO
ß-elemene, extracted from Rhizoma zedoariae, has been widely used as a traditional medicine for its antitumor activity against a broad range of cancers. However, the effect of ß-elemene in inflammation disorders has yet to be determined. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of ß-elemene in lipopolysaccharide (LPS)-induced murine macrophage cells RAW264.7. We found that the production of pro-inflammatory mediators, including interleukin-6(IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), induced by LPS was significantly suppressed by ß-elemene in a dose-dependent manner in RAW264.7 macrophage cell line. Also, ß-elemene inhibited LPS-induced nitric oxide synthase (iNOS) and interleukin-10 (IL-10) expression by RAW264.7, which was related to the down-regulation of Wnt/ß-catenin signaling pathway. Importantly, this study demonstrates that ß-catenin was significantly inhibited by ß-elemene, which appeared to be largely responsible for the down-regulation of Wnt/ß-catenin signaling pathway. Accordingly, the deletion of ß-catenin in primary macrophages reversed ß-catenin-elicited inhibition of immune response. Furthermore, ß-catenin expression and Wnt/ß-catenin signaling pathway induced by LPS in RAW264.7 was also significantly inhibited by α-humulene, one isomeric sesquiterpene of ß-elemene. α-humulene was also found to significantly inhibit LPS-induced production of proinflammatory cytokines. However, α-humulene showed more cytotoxic ability than ß-elemene. Collectively, our data illustrated that ß-elemene exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of ß-catenin, and also demonstrated the protective functions of ß-elemene in endotoxin-induced inflammation. ß-elemene may serve as potential nontoxic modulatory agents for the prevention and treatment of inflammatory diseases.