Screening the effective components of Ficus tikoua on the treatment of lipopolysaccharide induced acute lung injury mice by integrated UHPLC-Q-TOF-MS/MS and network pharmacology.

Acute lung injury (ALI) is a life‑threatening respiratory disease characterized by excessive inflammation, oxidative stress, and autophagic dysregulation. Traditional Chinese medicine has emerged as a promising strategy for managing respiratory inflammatory conditions. Ficus tikoua Bur. (FT), a well‑known ethnomedicinal prescription used for pneumonia in Guizhou, China, warrants investigation into its effects and mechanisms in ALI. This study integrated UHPLC‑Q‑TOF‑MS/MS chemical profiling, network pharmacology, molecular docking, and lipopolysaccharide‑challenged mouse model to characterize FT's bioactive constituents and therapeutic mechanisms. FT extract (FTE) significantly attenuated lung injury, reduced inflammatory cytokines (TNF‑α and IL‑6), and decreased oxidative stress markers (MPO and MDA). Network pharmacology and molecular docking identified stable interactions between core FT compounds and five key targets (mTOR, AKT1, PIK3CA, PIK3CB, and PIK3CD). Experimental validation further revealed that FTE inhibited PI3K/AKT overactivation, as evidenced by reduced p‑PI3K and AKT expression, while concurrently restoring autophagic homeostasis through downregulation of Beclin‑1 and LC3‑II/I and upregulation of p62. These findings demonstrate that FTE alleviates ALI through coordinated regulation of the PI3K/AKT pathway and autophagic homeostasis. Collectively, this study provides a mechanistic foundation for FT as a multi‑component therapeutic candidate against ALI and offers new perspectives for natural product‑based drug discovery.