Protective effect of chrysophanol on acute kidney injury in sepsis through NF-κB pathway
OBJECTIVE To explore the mechanism of chrysophanol against acute kidney injury(AKI)in sepsis and provide theoretical rationales for clinical treatment.METHODS The relevant targets of CHR for septic AKI were obtained through net-work pharmacology.Potential therapeutic targets of CHR for septic AKI were harvested through plotting a Venn diagram.The protein interaction network diagram of the targets was constructed by the databases of STRING and Cytoscape.The key therapeu-tic targets of CHR for septic AKI were obtained by arranging them in accordance with the degree.Then GO/KEGG enrichment analysis of key targets was performed by Metascape.Along with cell assays,lipopolysaccharide(LPS)was utilized for inducing HK-2 cells for a modeling of septic AKI for in vitro experimental validation.Cell viability was detected by CCK-8,apoptosis by Hoechst33258 stain,inflammatory factor expression by enzyme-linked immunosorbent assay(ELISA)and the protein expres-sions of Bcl-2,BAX and NF-κB p-p65 by Western blot.RESULTS A total of 78 common therapeutic targets of chrysophanol for septic AKI were identified.The results of KEGG enrichment analysis showed that signaling pathway of NF-κB pathway was involved.The results of in vitro experiments indicated that chrysophanol could improve cellular injury and apoptosis caused by LPS,suppress the release of inflammatory factors of TNF-α and IL-6,lower the protein expression of NF-κB p-p65 and blunt the activation of NF-κB pathway.CONCLUSION Chrysophanol may be a multi-target and multi-pathway treatment for septic AKI.And the therapeutic mechanism of chrysophanol for septic AKI is probably correlated with an inhibition of NF-κB signaling pathway activation.
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