Nano-Encapsulated Cordyceps militaris Grown on Germinated Black Bean Attenuates PM- and LPS-Induced Airway Inflammation

Exposure to particulate matter (PM) containing bacterial endotoxins triggers oxidative stress and inflammation in the respiratory epithelium. In this study, we investigated chitosan nanoparticle-encapsulated Cordyceps militaris grown on germinated Rhynchosia nulubilis (GCN) as a potential functional food–derived ingredient against PM- and lipopolysaccharide (LPS)-induced cellular damage in human lung epithelial cells. Nano-encapsulation significantly improved the antioxidant capacity and storage stability of the extract compared with the non-encapsulated form GRC. GCN markedly attenuated PM- and LPS-induced cytotoxicity and intracellular reactive oxygen species (ROS) generation in a dose-dependent manner, resulting in a therapeutic index approximately 4.5-fold higher than that of GRC. PPI network and hub gene analysis identified 120 inflammation-related genes associated with PM- and LPS-induced pulmonary responses enriched in inflammatory response, cytokine–cytokine receptor interaction, Toll-like receptor, and TNF signaling pathways. Protein-protein interaction network analysis revealed TNF, CXCL-10, IL-6, IL-1β, and CXCL-2 as key hub genes involved in these pathways. Consistent with these predictions, GCN significantly suppressed PM- and LPS-induced mRNA expression of TNF-α, CXCL-2, and TRPC6, and effectively inhibited MAPK-mediated NF-κB and AP-1 signaling pathways in A549 cells. Collectively, nano-encapsulation enhances the stability and bioactivity of Cordyceps militaris-based extracts and suggest that GCN may serve as a functional food-derived ingredient for protecting airway epithelial cells from oxidative stress and inflammation induced by environmental stressors.