Mechanism of Qibai Pingfei Capsule in ameliorating COPD-associated inflammation via the ABCA3/PPARγ/NF-κB pathway: A serum-targeted metabolomics and lipidomics study

Chronic obstructive pulmonary disease (COPD) is a global health issue driven by chronic inflammation. Although Qibai Pingfei Capsule (QBPF) shows clinical efficacy in COPD, its multi-component, multi-target nature complicates mechanistic studies. A COPD rat model was established using smoking, hypoxia, and swimming. Metabolomics and lipidomics based on ultra-high performance liquid chromatography coupled with electrospray ionization triple quadrupole-linear ion trap mass spectrometry (UHPLC-ESI-QTRAP-MS) revealed that QBPF alleviated COPD-associated metabolic disruptions, particularly in energy, amino acid, and lipid metabolism. Multivariate statistical analysis, cluster analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis intended to obtain ATP binding cassette subfamily A member 3 (ABCA3) as a key target. Western blot (WB) analysis, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) confirmed that QBPF upregulated the expression of ABCA3 and peroxisome proliferator-activated receptor gamma (PPARγ) in COPD rats, downregulated p-nuclear factor kappa B p65 (p-p65), and subsequently downregulated the expression of inflammatory factors such as interleukin-1 beta (IL-1β) and interleukin-17A (IL-17A), thereby alleviating COPD pulmonary inflammation. After transfection with small interfering RNA (siRNA) ABCA3, the expression of ABCA3 was knocked down and the upregulation of PPARγ by QBPF was weakened, thereby affecting its inhibitory effects on p65, IL-1β, and IL-17A. Our research results indicated that QBPF could upregulate the expression of ABCA3, leading to an increase in PPARγ and a decrease in p-p65, ultimately improving pulmonary inflammation in COPD.