Glabridin as a Potential Therapeutic Agent for COPD: Mechanistic Insights into JAK1/STAT1 Pathway Inhibition

Background Chronic obstructive pulmonary disease (COPD) is a common inflammatory disorder that is significantly aggravated by tobacco smoke exposure. Purpose This study aimed to explore the effect of glabridin (Glab) on the inflammatory response and explain the molecular mechanism of Glab in vitro model of human bronchial epithelial cells (16HBE) induced by cigarette smoke extract (CSE). Materials and Methods We constructed an in vitro model of COPD using CSE induction of 16HBE and applied Glab with differential concentration gradients to the model. Cell viability was assessed using the Cell Counting Kit-8 method. We also measured the apoptosis rate and the release level of inflammatory factors under each simulated condition, mainly based on flow cytometry, enzyme-linked immunosorbent assay, and Western blotting to evaluate the above parameters. Network pharmacology and molecular docking analyses were employed to predict Glab’s interactions with the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. These predictions were subsequently validated via gene knockdown experiments. Results Glab can reduce the negative effects of CSE on cells by inhibiting the expression of inflammatory factors. The effect of Glab was concentration-dependent. Molecular docking demonstrated Glab’s strong binding affinity for JAK1 at residues GLY263, GLY440, and ASN465. Glab treatment inhibited JAK1/STAT1 phosphorylation, and STAT1 knockdown abrogated Glab’s protective effects, confirming its target-specific action. Conclusion These findings highlight Glab’s potential as an anti-inflammatory agent for COPD by targeting the JAK1/STAT1 signaling pathway. Further studies are warranted to explore its clinical applicability in COPD management.