Phillyrin prevents sepsis-induced acute lung injury through inhibiting the NLRP3/caspase-1/GSDMD-dependent pyroptosis signaling pathway

• Phillyrin (PHI) preadministration significantly reduces sepsis-induced pulmonary edema, inflammation, and histological damage in mice, indicating its preventive potential against acute lung injury (ALI). • PHI suppresses the activation of the NLRP3/caspase-1/GSDMD pyroptosis pathway in alveolar epithelial cells, both in vivo and in vitro, highlighting its mechanism of action. • Molecular docking and surface plasmon resonance demonstrate that PHI directly binds to GSDMD protein, identifying GSDMD as a potential pharmacological target for PHI. • These findings support PHI as a promising therapeutic candidate for sepsis-induced ALI, offering a novel approach targeting pyroptosis.