摘要Objective:This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction(XFBD)in a mouse model of dampness-heat toxin pneumonia.By exploring how XFBD exerts its effects,we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action,thereby supporting its clinical application.Methods:Ultra-high-performance liquid chromatography and high-resolution mass spectrometry(HRMS)were employed to analyze the chemical constituents of XFBD.The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model,established through dampness-heat exposure and HCoV-229E infection.XFBD was administered orally,followed by assessments including lung index measurement,micro-CT imaging,viral load quantification,cytokine analysis,and histological evaluation via hematoxylin-eosin staining.Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD's pharmacological effects.A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway.Molecular docking and surface plasmon resonance(SPR)experiments confirmed the strong binding affinity between key XFBD components and PKA.Finally,PKA activators and inhibitors were applied in vitro to validate these mechanistic findings.Results:In vivo studies demonstrated that XFBD significantly reduced the lung index,improved the structural integrity of lung and tongue tissues,and decreased levels of proinflammatory mediators,including IL-6,IL-8,and TNF-α.Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation.The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects.Notably,Western blot,ELISA,molecular docking,and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression,thereby activating the cAMP/PKA signaling pathway in vitro.Conclusion:This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia.Its therapeutic effects are mediated,at least in part,through activation of the cAMP/PKA signaling pathway.These findings provide com-pelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.