Integrated network pharmacology, transcriptomics and proteomics unveils the mechanisms of Forsythiae Fructus against acute lung injury.

Acute lung injury (ALI) is a life-threatening respiratory disorder with high mortality. Forsythiae Fructus (FF), a traditional Chinese medicine widely used for respiratory diseases, shows therapeutic potential against ALI, yet its underlying mechanisms remain poorly understood from a multi-omics perspective. This study integrated network pharmacology, transcriptomics, and proteomics to elucidate the protective mechanisms of FF against ALI. The chemical profile of FF was characterized by UPLC-Q-TOF-MS/MS, and an LPS-induced ALI rat model was established for pharmacodynamic evaluation. The optimal dose group was selected for multi-omics analysis. A total of 95 compounds were identified, and integrated analysis revealed that 11 core components mediated anti-ALI effects by modulating 347 targets across 25 signaling pathways. Molecular docking and Western blot validation demonstrated that these targets are primarily associated with the PI3K-Akt/mTOR, MAPK/ERK/p-38, JAK-STAT, and PPARγ signaling pathways. This study provides a comprehensive multi-omics framework for understanding the mechanisms of FF against ALI.