促炎细胞因子
Wnt信号通路
肿瘤坏死因子α
连环素
炎症
化学
榄香烯
信号转导
脂多糖
白细胞介素
药理学
细胞因子
细胞生物学
生物
细胞凋亡
免疫学
生物化学
作者
Yangyi Fang,Yanhua Kang,Han Zou,Xiaxuan Cheng,Tian Xie,Liyun Shi,Hang Zhang
出处
期刊:Fitoterapia
[Elsevier]
日期:2018-01-01
卷期号:124: 92-102
被引量:38
标识
DOI:10.1016/j.fitote.2017.10.015
摘要
β-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 β-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 β-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-1β (IL-1β), induced by LPS was significantly suppressed by β-elemene in a dose-dependent manner in RAW264.7 macrophage cell line. Also, β-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/β-catenin signaling pathway. Importantly, this study demonstrates that β-catenin was significantly inhibited by β-elemene, which appeared to be largely responsible for the down-regulation of Wnt/β-catenin signaling pathway. Accordingly, the deletion of β-catenin in primary macrophages reversed β-catenin-elicited inhibition of immune response. Furthermore, β-catenin expression and Wnt/β-catenin signaling pathway induced by LPS in RAW264.7 was also significantly inhibited by α-humulene, one isomeric sesquiterpene of β-elemene. α-humulene was also found to significantly inhibit LPS-induced production of proinflammatory cytokines. However, α-humulene showed more cytotoxic ability than β-elemene. Collectively, our data illustrated that β-elemene exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of β-catenin, and also demonstrated the protective functions of β-elemene in endotoxin-induced inflammation. β-elemene may serve as potential nontoxic modulatory agents for the prevention and treatment of inflammatory diseases.
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