Yeast β-1,3/1,6 glucan regulates NRF2 to inhibit ferroptosis and ameliorates aspiration pneumonia in aged mice

Background Aspiration pneumonia (AP) is a common and serious respiratory disease among the elderly, with current treatments limited primarily to antibiotics and supportive care, highlighting a need for targeted therapies. Yeast β-1,3/1,6-glucan (YBG), a natural polysaccharide derived from yeast cell walls, holds immunomodulatory and antioxidant properties. However, its mechanism in AP remains unclear.Methods An AP model was established in aged C57BL/6 mice using HCl-treated pepsin and lipopolysaccharide (LPS), followed by YBG administration. Lung histopathology was assessed by H&E staining. Total protein concentration in bronchoalveolar lavage fluid (BALF) was measured, and inflammatory cytokines (IL-1β, IL-6) were detected by ELISA. Iron deposition was visualized via Prussian blue staining, and ferroptosis-related proteins (GPX4, SLC7A11) were analyzed by Western blotting (WB). MDA levels and SOD activity were also evaluated using specific kits. Additionally, an LPS-induced lung epithelial cell injury model was established to assess cell viability, apoptosis, and ferroptosis markers (MDA, SOD, GPX4, SLC7A11). Activation of the NRF2/HO-1 pathway was assessed by WB.Results In vivo, YBG significantly alleviated pathological lung injury, inflammation, and ferroptosis in aged mice. Mechanistically, YBG enhanced cell viability, reduced apoptosis, and suppressed ferroptosis in LPS-injured lung epithelial cells via activation of the NRF2/HO-1 pathway.Conclusion YBG ameliorates inflammation and lung injury in aged mice with AP by inhibiting ferroptosis through activation of the NRF2/HO-1 pathway, suggesting its potential as a therapeutic agent.