Abstract

Ethnopharmacological relevance Chronic obstructive pulmonary disease (COPD) is a frequently encountered respiratory disease. Its clinical symptoms are characterized by long-term coughing, expectoration, and other airway symptoms, resulting in significant harm. Linggan Wuwei Jiangxin Decoction (LGWWJXD) has the effects of warming the lungs, transforming fluid retention, and relieving cough and asthma, and is a classic prescription for treating COPD. Aim of the study This study aims to determine the mechanism of action of LGWWJXD in preventing and treating COPD. Materials and methods COPD rat models were established using a combination of exposure to cigarette smoke (CS), hypothermia, and lipopolysaccharide (LPS). Model rats were administered LGWWJXD. Histological changes in lung tissues were detected via hematoxylin-eosin (H&E) staining combined with transmission electron microscopy. Quantification of inflammatory factors in the bronchoalveolar lavage fluid, serum and cell culture medium were determined using enzyme-linked immunosorbent assays. The active ingredients of LGWWJXD and its components that could enter the systemic circulation were identified using UPLC-MS/MS. Metabolomic analysis characterized distinctive metabolites and associated pathways, and transcriptomics was used to identify differential genes and determine differential enrichment pathways. Core genes were identified through WGCNA combined with three machine learning algorithms. The interactions between cell subtypes was investigated through immune cell infiltration analysis and single-cell RNA sequencing. Molecular docking and molecular dynamics simulations were performed to screen key genes and core compounds. Subsequently, BEAS-2B cells were stimulated with CS and LPS to establish a COPD cell model, aiming to elucidate the mechanisms underlying the therapeutic effects of the key compounds. Finally, the aforementioned results were integrated to systematically explore the potential mechanism of L