Mechanistic study of cortex mori radices on alleviating inflammatory response in fibroblasts and enhancing lung function in COPD

Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition defined by persistent airway inflammation. While traditional Chinese medicine offers distinct advantages in its management, the pharmacological effects and mechanisms of cortex mori radices (CMR) in COPD remain largely unexplored. Methods A cigarette smoke-induced COPD rat model and a transforming growth factor‑β1 (TGF‑β1)‑stimulated MRC‑5 fibroblast model were established. To evaluate the therapeutic effects, multiple endpoint indicators were assessed, including histopathology by hematoxylin‑eosin (HE) staining; oxidative stress markers including malondialdehyde (MDA), glutathione peroxidase (GSH‑Px), and superoxide dismutase (SOD); inflammatory cytokines including tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), interleukin‑1β (IL‑1β), and monocyte chemoattractant protein‑1 (MCP‑1); and fibrosis and fibroblast activation by Transwell assay, wound healing assay, quantitative real‑time PCR (qRT‑PCR), and Western blot. Results Animal experiments confirmed that CMR alleviated lung injury in COPD rats, inhibited oxidative stress (reduced MDA levels and increased GSH-Px and SOD activities) and inflammatory factor levels (TNF-α, IL-6, IL-1β, MCP-1) ( P <0.001), upregulated E-cadherin expression, and downregulated N-cadherin, COL-1, ATF6, GRP78, and XBP1 ( P <0.05, P <0.01, P <0.001). Furthermore, in vitro rescue experiments using tunicamycin (TM) confirmed that ERS was successfully reactivated. Upon ERS activation, the CMR‑mediated inhibitory effects on TGF‑β1‑induced fibroblast activation, migration, invasion, oxidative stress, and inflammation were significantly reversed ( P < 0.05, P < 0.01, P < 0.001). Conclusion This study elucidates the mechanism by which CMR inhibits fibroblast inflammation and enhances lung function in COPD, highlighting its clinical potential as a promising candidate drug for combating COPD.