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

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 PGE₂, 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 PGE₂ 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.

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