110 / 2021-10-24 11:30:08

Fucoxanthin inhibits ferroptosis against LPS-induced RAW264.7 inflammation by regulating STAT3 signaling pathway

Fucoxanthin；,ferroptosis,STAT3,Inflammation

Background: Ferroptosis is a newly discovered mode of cell death different from apoptosis and necrosis, triggered by iron-dependent peroxidation accumulation, and plays an active role in the inflammatory response. Fucoxanthin is a natural carotenoid with abundant content, which has the characteristics of anti-inflammation, but whether it acts by regulating ferroptosis has not been reported.

Objective: The aim of this study was to investigate the protective effect of fucoxanthin on LPS-induced inflammation in RAW264.7 cells and its regulatory mechanism.

Methods: A network pharmacology analysis of fucoxanthin and ferroptosis was carried out combining the use of FerrDb database, PubChem database, CTD database, SwissTagertPrediction, and other databases. The intersection target genes and enriched pathways were predicted by target prediction, protein-protein interaction analysis, GO and KEGG pathway analysis. In vitro, mouse mononuclear macrophages (RAW264.7) were induced by lipopolysaccharide (LPS) to establish a cellular inflammation model and the effects of fucoxanthin on inflammation and ferroptosis were subsequently measured.

Results: The enrichment analysis of fucoxanthin-related target genes is closely related to the occurrence and development mechanism of ferroptosis. GO and KEGG enrichment analysis of the intersection genes of fucoxanthin acting on ferroptosis further found that fucoxanthin-related target genes are strongly related to the mechanism of ferroptosis, involving lipoxygenase pathway, hepoxilin biosynthetic process, arachidonic acid metabolic process, linoleic acid metabolic process, oxidation-reduction process and so on. In addition, In vitro, fucoxanthin can attenuate LPS-induced expression of inflammatory mediators and inflammatory factors in RAW264.7 cells. Moreover, ferroptosis can mediate LPS-induced inflammatory response in RAW264.7 cells, and fucoxanthin may reduce LPS-induced inflammatory response by inhibiting ferroptosis through regulating STAT3 signaling pathway.

Conclusion: Fucoxanthin attenuates LPS-induced ferroptosis through the STAT3 pathway, thereby inhibiting the inflammatory response.