Daphnetin alleviates renal inflammation, oxidative stress, and apoptosis in septic rats via the JAK2/STAT3 signaling pathway.

Abstract

Acute kidney injury (AKI) induced by sepsis is a critical condition with high morbidity, posing a significant challenge in clinical settings. Daphnetin (DAP), a natural compound, has demonstrated anti-inflammatory and antioxidant properties in various diseases. This study aims to explore the specific role and underlying mechanism of DAP in sepsis-induced AKI. Sepsis was induced in rats using the cecal ligation and puncture (CLP) method. Renal tissue samples were analyzed via hematoxylin and eosin staining for histopathological analysis and TUNEL assay for apoptosis detection. The expression of proteins associated with apoptosis or the JAK2/STAT3 pathway was determined via western blot analysis. Inflammatory cytokines were measured using ELISA kits. Oxidative stress markers were detected via biochemical analysis. Additionally, an in vitro sepsis model induced by lipopolysaccharide (LPS) was established to validate the effects of DAP. Cytotoxicity of DAP to HK-2 cells was determined using the CCK-8 assay, and cell apoptosis was analyzed via flow cytometry analysis. The results showed that DAP remarkably improved renal function in septic rats; it reduced the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6), attenuated oxidative stress, and suppressed cell apoptosis in renal tissues. DAP inhibited the activation of JAK2/STAT3 signaling in both septic rats and LPS-stimulated HK-2 cells. in vitro experiments showed that DAP or AG490 (a JAK2 inhibitor) alleviated LPS-induced apoptosis, inflammation, and oxidative stress. In conclusion, DAP attenuates sepsis-induced AKI by reducing inflammation, oxidative stress, and apoptosis via the inactivation of the JAK2/STAT3 pathway.