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 the lung structure from damage. Mechanistically, based on the results of RNA-sequencing and network pharmacology and subsequent experiments MFJHQ inhibited 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 therapeutic strategy for COPD.