The Modified Fangji Huangqi Decoction Ameliorates Chronic Obstructive Pulmonary Disease (COPD) by Down-regulating IL-33 Expression to inhibit Neutrophil Recruitment

Ethnopharmacological relevance Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder with complex pathogenesis and multiple contributing factors. Modified Fangji Huangqi decoction (MFJHQ), a traditional Chinese medicine formula, has demonstrated clinical efficacy in COPD treatment. However, the pharmacological roles and underlying mechanisms of MFJHQ in treating COPD remain unclear. Aim of study To investigate the therapeutic effects and molecular mechanisms of MFJHQ in the treatment of COPD. Methods COPD models were established in vitro using alveolar organoid (AOs) and 16 Human Bronchial Epithelial (16HBE) cells separately, induced by porcine pancreatic elastase (PPE) and in vivo in PPE-induced COPD mice. MFJHQ was administered via gavage for three weeks. RNA-sequencing and network pharmacology were employed to elucidate potential mechanisms of action. Results In vitro , MFJHQ enhanced epithelial barrier integrity by reducing permeability and upregulating zonula occludens-1 (ZO-1) expression. In vivo, MFJHQ effectively improved pulmonary function, alleviated emphysema and airway obstruction, and protected lung tissue structure from damage. Mechanistically, RNA-sequencing and network pharmacology predicted, and subsequent experiments confirmed, that MFJHQ inhibited PPE-induced IL-33 and its downstream NF-κB signaling and CXCL5 expression thereby reducing neutrophil recruitment in lung tissues. Conclusion MFJHQ ameliorates COPD progression by inhibiting neutrophil infiltration through suppression of IL-33 and CXCL5 providing a new multi-targeted therapeutic strategy for COPD.