The Protective Effects of Dose-Dependent Umbelliferone Application on CLP-Induced Acute Lung Injury (ALI) Model.

Abstract

This study aimed to evaluate the beneficial effects of umbelliferone (UMB) (25, 50, and 100 mg/kg) in a cecal ligation and puncture (CLP)-induced rat model of sepsis, focusing on inflammation and oxidative stress mechanisms. Thirty-six Wistar albino rats were randomly assigned to six groups: Control, Sham, Sepsis, and Sepsis treated with three different doses of umbelliferone. Inflammatory cytokines were measured by ELISA, oxidative stress markers by tissue biochemistry, while protein expression and immune cell density were assessed using Western blotting and immunohistochemistry. Sepsis markedly increased pro-inflammatory cytokines, oxidative stress parameters, and NF-κB/CD68 immunopositivity, while reducing antioxidant defenses. UMB administration dose-dependently reversed these alterations, reducing pro-inflammatory cytokines, enhancing anti-inflammatory cytokines, restoring antioxidant balance, and significantly decreasing Nrf2 expression. Umbelliferone confers protection against sepsis-induced acute lung injury through multiple mechanisms, including suppression of NF-κB signaling, modulation of cytokine balance, and activation of the Nrf2/Keap1/HO-1 pathway. These findings highlight its potential as a natural therapeutic candidate for sepsis-related organ injury.