UHPLC -Q-Orbitrap HRMS Integrated with Network Pharmacology Reveals the Anti-COPD Mechanism of Jianzhong Peiyuan Decoction and Functional Validation of Core Component Luteolin.

OBJECTIVE: Jianzhong Peiyuan Decoction, based on Shenling Baizhu Powder, is commonly used for stable COPD in Guizhou. However, its chemical composition and pharmacodynamics are not well understood. This study aims to explore its pharmacodynamic basis and multi-target pathways in COPD treatment and to confirm the intervention effect of its key active ingredient, luteolin, through in vitro cell experiments. METHODS: UHPLC-Q-Orbitrap HRMS identified the chemical constituents of Jianzhong Peiyuan Decoction. Network pharmacology screened core components, identified drug-disease targets, and conducted PPI network, GO function, and KEGG pathway analyses. Molecular docking and dynamics simulations assessed core components' binding stability to key targets. 16HBE cell injury model induced by cigarette smoke extract was used to examine the expression of key targets in the SRC/MAPK1/Akt/STAT3 and PPARγ/CD36/ABCA1 pathways via RT-qPCR. RESULTS: Study identified 497 chemical components in Jianzhong Peiyuan Decoction, including 9 key active ones such as Longikaurin A, kaempferol, and luteolin. It found 675 potential targets for COPD treatment, with six core targets-SRC, ESR1, AKT1, MAPK1, STAT3, and EGFR-highlighted through PPI network analysis. KEGG pathway enrichment pointed to the lipid and atherosclerosis pathway as crucial. Molecular docking and simulations showed strong binding of the active ingredients, especially luteolin, to the core targets. In vitro experiments on 16 HBE cells in a CSE-induced COPD model showed overexpression of SRC, AKT1, MAPK1, STAT3, EGFR, and CD36 mRNA, while ESR1, PPARγ, and ABCA1 mRNA were reduced. Luteolin was found to normalize these gene expressions in a dose-dependent manner. CONCLUSION: Jianzhong Peiyuan Decoction aids in COPD treatment through multiple components, targets, and pathways. Luteolin, a key ingredient, mitigates cigarette smoke-induced bronchial injury by modulating inflammatory and lipid metabolism pathways. This study clarifies the Decoction's material basis and molecular mechanism in treating stable COPD, offering experimental and theoretical support for its clinical use and quality standards.