Exploring the mechanism of astaxanthin against lipopolysaccharide-induced acute lung injury by network pharmacology and experimental validation

Abstract BackgroundAcute lung injury (ALI) is a leading cause of morbidity and mortality in respiratory disease. Astaxanthin, a natural antioxidant xanthophyll carotenoid, has been shown to possess anti-inflammatory activity. However, poor evidence has been reported that whether it has protective effects against ALI.Methods A network pharmacology analysis was carried out combining the construction of the GeneCards database and the Pharmmapper database, The potential active compounds and targets were predicted by compound-target prediction, protein-protein interaction analysis, GO and KEGG pathway analysis. Then, the anti-inflammation effect of astaxanthin was investigated in LPS-induced RAW264.7 cells in vitro and LPS-induced ALI mice in vivo.ResultsThe results screened by GO and KEGG enrichment analysis suggested that astaxanthin had extensive associations with 25 known therapeutic targets of ALI. These target genes were further found to be associated with pathways involved in inflammatory pathways in ALI, such as the Toll-like receptor signal pathway, TNF signal pathway, Hif signal pathway, and NF-Kappa B signal pathway. Pre-treatment with astaxanthin inhibited the TLR4/MyD88 signaling pathway and attenuated LPS-increased inflammatory factors in vitro. Furthermore, the administration of astaxanthin significantly protected lung injury in vivo. Subsequently, we validated astaxanthin binds to the TLR4 pocket using molecular docking. ConclusionTaken together, astaxanthin exerts impressively protective effects on LPS-induced ALI in vitro and in vivo via suppressing the TLR4/MyD88 signaling pathway.