The Inhibitory Effects of <i>Cordyceps militaris</i> ARA301 Extract on Lipopolysaccharide-Induced Lung Injury <i>in vivo</i>

Lung injury is a critical health concern associated with severe inflammatory responses and tissue damage that can weaken respiratory function and potentially become life-threatening in severe cases. This study aimed to establish a mouse model of lung injury induced by lipopolysaccharides (LPS) derived from <i>Klebsiella pneumoniae</i> and to evaluate whether <i>Cordyceps militaris</i> ARA301 extract (CME) can prevent lung injury. CME was orally administered to mice for three consecutive days, followed by intranasal LPS administration. Mice were sacrificed 24 h later to analyze immune cell alterations and inflammatory responses through bronchoalveolar lavage fluid (BALF) and tissue analyses. CME administration inhibited immune cell infiltration, tissue fibrosis, and excessive mucus deposition induced by intranasal LPS administration. Furthermore, CME suppressed the expression of mucin 5AC (MUC5AC), a protein involved in mucus production, as well as the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in lung tissues. In BALF, CME reduced the production of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-X-C motif chemokine ligand 1 (CXCL1), which were elevated due to LPS administration. Additionally, CME decreased the total immune cell, neutrophil, monocyte, and eosinophil numbers in BALF. The anti-inflammatory activity of CME was evaluated <i>in vitro</i> using RAW 264.7 cells. CME treatment reduced the secretion of pro-inflammatory cytokines induced by LPS and inhibited the phosphorylation of p65, inhibitor of kappa B alpha (IκBα), and IκB kinase alpha (IKKα). These findings suggest that CME has potential as a functional health supplement effective in preventing lung injury.