Jinwei Guben Formula (Jinwei Formula II) Modulates Neutrophil Extracellular Trap Formation and Enhances Glucocorticoid Efficacy in COPD Through HDAC2 Regulation

INTRODUCTION: Neutrophil extracellular traps (NETs) contribute to chronic inflammation in chronic obstructive pulmonary disease (COPD). Jinwei Guben Formula (JWGB) is a clinically used TCM for COPD, but its mechanism regarding NETs and glucocorticoid sensitivity is unclear. This study aimed to investigate whether JWGB modulates NETs formation and glucocorticoid efficacy via HDAC2 in COPD. METHODS: An integrated approach combining UHPLC-MS/MS, network pharmacology, molecular docking, and human neutrophil experiments was used. RESULTS: We identified 168 compounds in JWGB. Network analysis predicted 42 active ingredients and highlighted the NETs formation pathway. Key ingredients showed strong binding to HDAC2 and MPO. Experimentally, JWGB inhibited CSE-induced NETs release and inflammation. Notably, JWGB upregulated HDAC2 expression in COPD neutrophils and synergized with methylprednisolone, allowing a low dose (100 μM) to match the efficacy of a high dose (500 μM). DISCUSSION: Our findings reveal that JWGB alleviates COPD by simultaneously inhibiting NET formation and restoring HDAC2 function. This dual action provides a mechanistic basis for its clinical efficacy and suggests its potential as a steroid-sparing strategy to overcome glucocorticoid resistance. CONCLUSION: JWGB may alleviate neutrophilic inflammation in COPD by inhibiting NET formation and upregulating HDAC2. Its synergy with glucocorticoids suggests potential as a steroid- sparing therapy.