β-elemene attenuates macrophage activation and proinflammatory factor production via crosstalk with Wnt/β-catenin signaling pathway
Autor: | Yanhua Kang, Xiaxuan Cheng, Han Zou, Liyun Shi, Tian Xie, Yangyi Fang, Hang Zhang |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Lipopolysaccharide Interleukin-1beta Anti-Inflammatory Agents Down-Regulation Nitric Oxide Synthase Type II Inflammation Biology Proinflammatory cytokine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery medicine Animals Wnt Signaling Pathway Pharmacology Interleukin-6 Tumor Necrosis Factor-alpha Macrophages Wnt signaling pathway LRP5 General Medicine Macrophage Activation Cell biology Nitric oxide synthase RAW 264.7 Cells 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Tumor necrosis factor alpha medicine.symptom Signal transduction Sesquiterpenes |
Zdroj: | Fitoterapia. 124:92-102 |
ISSN: | 0367-326X |
Popis: | 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. |
Databáze: | OpenAIRE |
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