Chaihu-Guizhi Decoction Attenuates Airway Remodelling in COPD Mice Via The TGF-β1/Smads Signalling Pathway: An Integrated Proteomic and Metabolomic Analysis

Jiuwang Yu; Xiaodong Wu; Zeyu Chen; Chenxu Zhai; Jinxiang A; Yuping Zhang;

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ABSTRACT

Chronic obstructive pulmonary disease (COPD) is characterised by persistent airway injury and remodelling, and the mechanisms by which Chai-Hu-Gui-Zhi Decoction (CGD) acts in COPD remain unclear. This study investigated whether CGD attenuates airway remodelling through the TGF-β1/Smads-EMT-ECM signalling axis. A mouse COPD model was established by cigarette-smoke exposure plus intranasal lipopolysaccharide. After model induction, mice received dexamethasone acetate or low-, medium- or high-dose CGD for 28 days. UHPLC-MS/MS, network pharmacology, molecular docking, molecular dynamics, proteomics, metabolomics, ELISA, western blotting, RT-PCR, pulmonary function testing and histopathology were integrated. CGD dose-dependently improved pulmonary function and lung pathology and reduced BALF total protein, NO, VEGF, IFN-γ, MPO, CXCL1 and serum 8-OHdG. Multi-omics and network analyses implicated phenylalanine/tyrosine/tryptophan biosynthesis, the histidine-glutamate-hypoxanthine axis, MAPK, PI3K-Akt and TGF-β1-related pathways. Validation showed that CGD decreased TGF-β1, p-SMAD2/3, SMAD2/3, MMP-9 and TIMP-1; increased SMAD7 and E-cadherin; and regulated Smad2/Smad3/Smad7 mRNA. CGD may attenuate COPD airway remodelling, in association with suppressed TGF-β1/Smads signalling, restored SMAD7-mediated feedback, limited EMT and rebalanced ECM remodelling.

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