Bioactive Polysaccharides and Phlorotannins from <i>Eisenia bicyclis</i> Alleviate Particulate Matter (PM) _2.5 -Induced Chronic Lung Injury by Regulating Inflammatory and Fibrotic Pathways

This study investigated the protective effects of the ethanolic extract of <i>Eisenia bicyclis</i> (EB) against chronic pulmonary toxicity induced by particulate matter (PM_2.5) exposure in mice. EB contains phlorotannins, including dieckol and phlorofucofuroeckol A, sulfated polysaccharides, and lipid and amino acid derivatives. Male BALB/c mice were exposed to aerosolized PM_2.5 for 5 h daily over a repeated-dose period, and EB was administered orally. The administration of EB significantly ameliorated PM_2.5-induced lung damage by restoring antioxidant defense systems and decreasing serum levels of inflammatory cytokines. EB also suppressed mitochondrial dysfunction and apoptotic signaling. Furthermore, EB attenuated the expression of inflammatory markers, including TLR4, TNF-α, IL-1β, and COX-2, and attenuated the activation of fibrotic signaling pathways via the TGF-β/Smad axis. <i>In vitro</i> experiments using A549 cells further supported these findings, demonstrating that EB and its phlorotannin components (dieckol, 6,6'-bieckol, and 6,8'-bieckol) restored cell viability, reduced inflammatory cytokines, and modulated the Nrf2/HO-1 pathway together with fibrotic genes and proteins. These findings suggest that EB, which contains bioactive compounds, may be a promising functional material candidate for mitigating chronic lung injury caused by environmental toxicants such as PM_2.5.