Mechanism study of naringenin in treating sepsis-induced kidney injury based on network pharmacology

This study explored naringenin's therapeutic mechanisms in sepsis-induced AKI via network pharmacology. An integrative bioinformatics pipeline identified targets, mapped interactomes, and validated results via molecular docking. The efficacy was validated using a cecal ligation and puncture-induced AKI mouse model. Histopathological changes were assessed through hematoxylin-eosin staining. Biochemical parameters, including blood urea nitrogen (BUN) and creatinine (Cr), were quantified. Pro-inflammatory mediators (IL-1 and TNF-?) were evaluated via ELISA, while Nrf2 and HO-1 protein expression was determined through Western blot analysis. The network pharmacology analysis revealed 3,449 potential therapeutic targets of naringenin in AKI treatment. Target analysis demonstrated significant associations with oxidative stress response and apoptotic signaling cascades. KEGG pathway analysis highlighted the involvement of the Nrf2/HO-1 signaling axis in renal injury. Experimental results showed that naringenin improved pathological changes in AKI mice, down regulated serum BUN and Cr levels, reduced inflammatory factors IL-1 and TNF- ? levels and decreased the expression of Nrf2 and HO-1 proteins in sepsis-related AKI. The therapeutic efficacy of naringin in AKI is mediated through pleiotropic effects on multiple targets and signaling cascades, with its renoprotective mechanism primarily involving the regulation of Nrf2/HO-1 pathway-dependent oxidative stress reduction.