Sophoridine alleviates spleen injury in sepsis by inhibiting ASK1-mediated inflammation, oxidative stress, and apoptosis.

Abstract

Sepsis is a severe systemic inflammatory condition characterized by infection, and marked by high morbidity and mortality. Injury to the spleen resulting from sepsis disrupts immune defense functions, exacerbates systemic inflammatory dysregulation, and contributes to multiple organ failure, thereby substantially increasing patient mortality. Sophoridine (SR), a naturally occurring alkaloid derived from Sophora flavescens, exhibits anti-inflammatory, antioxidant and neuroprotective effects. This study investigated the protective effects of SR against sepsis-induced splenic damage and elucidated its underlying mechanisms. A murine sepsis model was established using cecal ligation and puncture (CLP), and SR was administered to assess its efficacy. Histological analysis demonstrated that SR markedly ameliorated structural damage to splenic tissue in mice subjected to CLP. Quantitative PCR (qPCR), dihydroethidium (DHE) staining, and TUNEL assays revealed that SR significantly reduced the mRNA levels of pro-inflammatory mediators, including Tnf, Il6, Il1b and Nos2, while increasing the mRNA level of the anti-inflammatory mediator Il10. Furthermore, SR substantially reduced reactive oxygen species (ROS) production and apoptosis. We also established an in vitro model by stimulating J774A.1 cells with lipopolysaccharide (LPS). Results from Western blotting, qPCR and flow cytometry analyzes indicated that the beneficial effects of SR on LPS-induced inflammation, oxidative stress and apoptosis were substantially attenuated by overexpression of ASK1. In conclusion, SR alleviates sepsis-induced splenic injury by suppressing inflammation, oxidative stress, and apoptosis through the inhibition of ASK1, thereby offering a potential therapeutic approach for the management of splenic injury in sepsis.