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

Abstract

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.

Key Findings

• Yeast β-1,3/1,6-glucan (YBG) significantly alleviated pathological lung injury, inflammation, and ferroptosis in aged mice with aspiration pneumonia.
• YBG enhanced cell viability, reduced apoptosis, and suppressed ferroptosis in LPS-injured lung epithelial cells.
• The protective effects of YBG are mediated through activation of the NRF2/HO-1 antioxidant pathway.

Clinical Significance

Citation

Li Qin, Li Chongjin, Yang Liet al.. Yeast β-1,3/1,6 glucan regulates NRF2 to inhibit ferroptosis and ameliorates aspiration pneumonia in aged mice. Biochimica et biophysica acta. General subjects. 2026-Oct-02.