AUTHOR=Gou Xuan , Zhang Wei , Wang Lele , Tan Caixia , Wei Hong , Wang Xinmin , Zhang Le 

TITLE=Chrysophanol promotes M2 polarization and inhibits M1 polarization through the NF-κB signaling pathway to attenuate sepsis-associated acute kidney injury

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1641068

DOI=10.3389/fphar.2025.1641068

ISSN=1663-9812

ABSTRACT=ObjectiveSepsis-associated acute kidney injury (SA-AKI) is a frequent and severe complication in septic patients. This study combines network pharmacology with in vitro and in vivo experiments to preliminarily investigate the protective effect of chrysophanol (CHR) on SA-AKI and its mechanism, aiming to find new therapeutic targets and strategies for SA-AKI treatment.MethodsHK-2 cells were used to investigate CHR’s inhibitory effects on SA-AKI in vitro using CCK-8 assay, Hoechst33258 staining, ELISA, Western blot. In vivo experiments were performed using a septic mouse model, and the therapeutic effect of CHR on SA-AKI and its effect on macrophage polarization were investigated using Hematoxylin and Eosin staining, ELISA, Western blot, and quantitative real-time PCR. Predicting the possible differentially expressed genes and pathways of CHR protecting SA-AKI through network pharmacology. Finally, these pathways were further validated in in vitro experiments by ELISA, Western blot and indirect immunofluorescence staining.ResultsCHR can inhibit LPS-induced injury and apoptosis in HK-2 cells, suppress the expression of inflammatory cytokines TNF-α and IL-6, and enhance its anti-apoptotic and anti-inflammatory effects on HK-2 cells through modulation of macrophages; in in vivo experiments, we obtained the same results that CHR effectively counteracted SA-AKI and played a protective role against mice exerting a protective effect. In addition, based on predictions from network pharmacology and validation from cellular experiments, CHR may exert these effects by inhibiting the NF-κB signalling pathway.ConclusionCHR may protect SA-AKI by inhibiting the NF-κB signalling pathway, promoting M2 macrophage polarisation and inhibiting M1 macrophage polarisation.