Polygonum multiflorum Inhibits Pulmonary Inflammation and Fibrosis in PM2.5-Induced Dysfunction Through the Regulation of the TLR4/TGF-β1 Signaling Pathway in Mice

Industrial development has improved living standards; however, mortality associated with fine particulate matter (PM_2.5) exposure continues to rise. Despite increasing awareness of its health risks, effective strategies to mitigate PM_2.5-induced pulmonary damage remain limited. This study examines the protective properties of an ethanolic extract from <i>Polygonum multiflorum</i> (EPM) in preventing pulmonary dysfunction induced by PM_2.5, as well as its possible use as a dietary intervention to improve respiratory health. The physiological compounds in EPM were identified using ultra-performance liquid chromatography, and its protective effects were evaluated via in vitro assays using A549 and RPMI 2650 cells. The antioxidant system and mitochondrial function were further analyzed in the lung tissues of PM_2.5-exposed BALB/c mice, with molecular mechanisms elucidated by Western blot analysis. The main bioactive compounds identified in EPM included 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside. EPM modulated the Nrf2 signaling pathway, enhancing antioxidant defense by regulating the expression of antioxidant-related proteins. Furthermore, EPM exhibited protective effects against inflammation, apoptosis, and fibrosis through the TLR4/p-JNK and TGF-β1 signaling pathways. These findings suggest that EPM exerts protective effects against PM_2.5-induced oxidative stress and inflammation and may be used as a functional food ingredient for respiratory health.