Stibene glucoside prevents PM caused pulmonary fibrosis by Pseudo hypoxia, autophagy and NF-κB signal pathways.

Although the association between PM exposure and pulmonary fibrosis is well-documented, the underlying molecular mechanisms remain poorly understood, and effective preventive strategies against PM-induced pulmonary toxicity are yet to be established‌. This study investigated the role of reactive oxygen species (ROS)-mediated pseudo-hypoxia signaling and NF-κB pathway activation in PM-triggered epithelial-mesenchymal transition (EMT) and fibrosis, alongside the therapeutic potential of the antioxidant compound stilbene glucoside (TSG). ‌In vivo‌, C57BL/6 mice exposed to PM for two months developed pulmonary fibrosis, with transcriptomic analysis revealing significant alterations in pathways associated with carbohydrate metabolism, cancer signaling, and immune-related diseases‌. Concurrently, upregulated expression of EMT markers (fibronectin, vimentin), glycolysis-related genes (PKM, LDHA), and inflammatory cytokines (TGF-beta) was observed in lung tissues‌. ‌In vitro‌, PM induced EMT in BEAS-2B cells via ROS-driven mitochondrial membrane potential collapse, mitophagy, HIF-1α activation, and NF-κB-mediated inflammation, which collectively promoted a metabolic shift toward glycolysis‌. Notably, TSG treatment attenuated PM-induced pulmonary fibrosis by suppressing ROS accumulation, pseudo-hypoxia signaling, and NF-κB pathway activation. These effects correlated with restored mitochondrial function and normalized glucose metabolism in cellular models‌. ‌We come to the conclusion that PM exacerbates pulmonary fibrosis through ROS/HIF-1α and NF-κB axis-driven EMT and metabolic reprogramming. TSG, as a multifunctional antioxidant, represents a promising prophylactic agent against PM-associated pulmonary damage‌.