Coix Seed Attenuates Acute Lung Injury via NLRP3 Signaling Pathway: Efficacy, Active Components, and Mechanisms

Coix seed is a medicinal and nutritional resource, but its protective effects against acute lung injury (ALI) remain unclear. This study investigated the efficacy, active components, and mechanisms of Coix seed extract (CSE) against ALI, focusing on the NLRP3 signaling pathway. The therapeutic efficacy of CSE was evaluated in a murine model of ALI. Liquid chromatography-mass spectrometry identified 32 components in CSE, which were then analyzed via network pharmacology, molecular docking, and molecular dynamics simulations for target prediction and drug-likeness evaluation. In vivo effects on NLRP3 pathway proteins were also examined. CSE decreased serum levels of TNF-α and IL-1β, pulmonary levels of IL-1β and IL-18, indicating systemic and local inflammatory suppression. Furthermore, CSE downregulated the expression of NLRP3, Caspase-1, and GSDMD-N in lung tissues, suggesting inhibition of NLRP3 inflammasome-driven pyroptosis. Network analysis screened 35 core targets and 4 NLRP3-related key targets involved in pathways regulating inflammation, proliferation, and oxidative stress. Molecular docking and dynamics simulations further corroborated the "component-target-disease" interactions within this network. Drug-likeness evaluation identified 12 promising compounds, including syringaldehyde, tangeretin, and eriodictyol. Collectively, these findings demonstrate that CSE alleviates ALI by suppressing both inflammation and pyroptosis through multiple pathways, with NLRP3 as a central mechanistic hub. The identification of bioactive compounds with favorable pharmacokinetic properties provides a chemical basis for quality control and supports potential application of CSE as a functional food ingredient in the management of pulmonary inflammatory conditions.