Integrative analysis of Huangjing-Gegen compatibility in treating COPD: a network pharmacology, molecular docking, and experimental study.

Chronic obstructive pulmonary disease (COPD) remains a major global health challenge. This study explored the therapeutic mechanisms of Huangjing (Polygonati Rhizoma) and Gegen (Puerariae Lobatae Radix), two food-medicine homologous herbs with potential in COPD management. Integrating network pharmacology, serum pharmacochemistry, molecular docking, and experimental validation, we identified 239 shared targets and the PI3K/AKT pathway as a potential key mechanism. UHPLC Q-Exactive Orbitrap MS revealed 66 compounds, 14 of which were absorbed into circulation. In vivo, Huangjing-Gegen appeared to improve lung function (PaO2 increased by 28.3%, PaCO2 decreased by 22.7%), alleviate pathology, and reduce inflammation through downregulating TNF-α (by 21.4%), IL-6 (by 30.7%), and IL-1β (by 29.3%) and suppressing the EGFR-PI3K/AKT pathway. Molecular docking provided supportive evidence for strong binding between absorbed puerarin derivatives and core targets. These findings suggest that the PI3K/AKT pathway may play a central role in the therapeutic effects of Huangjing-Gegen against COPD.