4.7 Article

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

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 107, Issue -, Pages 1151-1159

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.08.094

Keywords

Chelidonine; Anti-inflammation; Toll-like receptor 4; Nuclear factor-kappa B; NLRP3 inflammasome

Funding

  1. National Natural Science Foundation of China [81260139, 81060073, 81560275, 61562021, 30560161]
  2. Hainan special projects of Social Development [2015SF39]
  3. Hainan Natural Science Foundation Innovation Research Team Project [2018CXTD350]
  4. Hainan Association for academic excellence Youth Science and Technology Innovation Program [201515]
  5. Hainan Natural Science Foundation of China [805106]
  6. Ministry of Personnel scientific and technological activities subject students project funds

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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(2), as well as iNOS and COX-2 mRNA and protein expression. In addition, pro-inflammatory cytokines induced by LPS, such as TNF alpha and IL-6 were also attenuated by chelidonine. What's more, LPS-induced activation and degradation of I kappa B alpha 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 TNF alpha, IL-6 and PGE(2) 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-kappa B signaling pathway disturbed by chelidonine.

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