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白屈菜碱通过抑制 RAW264.7 巨噬细胞中的 TLR4/NF-κB 信号通路抑制 LPS 诱导的炎症介质产生。

Chelidonine suppresses LPS-Induced production of inflammatory mediators through the inhibitory of the TLR4/NF-κB signaling pathway in RAW264.7 macrophages.

机构信息

Department of Cardiology, Hainan General Hospital, Haikou 570102, China.

Department of Nephropathy, Children's Medical Center, The Second Xiangya Hospital, Cal South University, Changsha 410000, China.

出版信息

Biomed Pharmacother. 2018 Nov;107:1151-1159. doi: 10.1016/j.biopha.2018.08.094. Epub 2018 Aug 28.

Abstract

Chelidonine is one of the alkaloids of Chelidonium majus, which has broad pharmacological activities, including anti-inflammatory. Despite chelidonine has been shown to exhibit anti-inflammatory activity, the molecular mechanisms are not yet fully elucidated. In this paper, we used RAW264.7 macrophages and mice to investigate the anti-inflammatory effects of chelidonine. Firstly, we found that chelidonine significantly suppressed LPS-induced the production of NO and PGE, as well as iNOS and COX-2 mRNA and protein expression. In addition, pro-inflammatory cytokines induced by LPS, such as TNFα and IL-6 were also attenuated by chelidonine. What's more, LPS-induced activation and degradation of IκBα followed by translocation of the p65 from the cytoplasm to the nucleus were attenuated by chelidonine. Furthermore, chelidonine even significantly inhibited TLR4 expression induced by LPS. Finally, we verified that chelidonine striking ly decreased serum TNFα, IL-6 and PGE levels in LPS stimulated mice. Taken together, this study demonstrated that chelidonine may suppressed the LPS-induced inflammatory response both in vitro and in vivo, which was relating to TLR4/NF-κB signaling pathway disturbed by chelidonine.

摘要

白屈菜碱是白屈菜中的一种生物碱,具有广泛的药理活性,包括抗炎作用。尽管白屈菜碱已被证明具有抗炎活性,但分子机制尚未完全阐明。在本文中,我们使用 RAW264.7 巨噬细胞和小鼠来研究白屈菜碱的抗炎作用。首先,我们发现白屈菜碱能显著抑制 LPS 诱导的 NO 和 PGE 的产生,以及 iNOS 和 COX-2 mRNA 和蛋白表达。此外,白屈菜碱还能减弱 LPS 诱导的促炎细胞因子 TNFα 和 IL-6 的产生。更重要的是,LPS 诱导的 IκBα 的激活和降解,以及 p65 从细胞质向细胞核的转位,也被白屈菜碱所减弱。此外,白屈菜碱甚至能显著抑制 LPS 诱导的 TLR4 表达。最后,我们验证了白屈菜碱能显著降低 LPS 刺激的小鼠血清中 TNFα、IL-6 和 PGE 的水平。综上所述,本研究表明,白屈菜碱可能通过干扰 TLR4/NF-κB 信号通路,抑制 LPS 诱导的体外和体内炎症反应。

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