Abstract

Background Qingfei Jiedu Huatan Formula (QJHF) has demonstrated efficacy in reducing the clinical stabilization time for pneumonia patients, decreasing ICU durations, and enhancing patients' quality of life. Objective Protecting the alveolar epithelial barrier is a proven strategy for improving pneumonia outcomes. This study aims to investigate the protective effects and underlying mechanisms of QJHF on the alveolar epithelial barrier in pneumonia. Methods A mouse model of pneumonia and acute lung injury was established via tracheal instillation of Klebsiella pneumoniae and LPS to evaluate the therapeutic effects of QJHF. Additionally, a TNF-α-induced alveolar epithelial cell barrier injury model was employed to explore the molecular mechanisms underlying QJHF's protective effects. Transcriptomics combined with network analysis was utilized to identify the active components and mechanisms of action for QJHF Molecular docking and molecular dynamics analyses elucidated the binding interactions between Ginsenoside Rb1 (GRb1) and target proteins, while the application of an Nrf2 inhibitor clarified the role of Nrf2 activation in GRb1-mediated alveolar barrier protection. Results QJHF significantly ameliorates Klebsiella pneumoniae-induced pneumonia in mice by improving lung tissue damage, reducing inflammatory cell infiltration, and decreasing levels of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, QJHF upregulates the expression of cell junction proteins ZO-1 and OCLN, thereby protecting the alveolar epithelial barrier. Similarly, QJHF mitigates LPS-induced lung damage, inflammation, and alveolar epithelial barrier dysfunction. Through integrating serum component profiling, network pharmacology, and lung transcriptomics revealed that 12 constituents in QJHF may interact with Nrf2 to modulate oxidative stress and apoptosis signaling pathways. Both