Integrated network pharmacology-metabolomics deciphers therapeutic mechanisms of Fritillaria thunbergii Miq. in pneumonia treatment

Chunlan Tang^1*Hang Hong¹Jiahui Zhu¹Jianying Wang¹Weina Ren²Donghui Chu¹Shuang Wang¹Jinyue Zhou¹Pengju Liu¹

• ¹Ningbo University, Ningbo, China
• ²The First Affiliated Hospital of Ningbo University, Ningbo, China

Pneumonia remains a leading global cause of mortality, underscoring the urgent need for novel therapeutic strategies amid rising drug-resistant pathogens and pandemic-related challenges. Fritillaria thunbergii Miq. (F. thunbergii Miq.), a traditional remedy for respiratory disorders, exhibits potential against pneumonia, yet its bioactive components and mechanistic underpinnings are poorly understood. This study integrated network pharmacology and metabolomics to elucidate material basis and therapeutic mechanisms of F. thunbergii Miq.. Through network pharmacology screening, eight core bioactive compounds and eleven key targets were identified, while nontargeted metabolomics revealed eight dysregulated metabolites associated with glutamine metabolism, inflammation, and oxidative stress. In LPS-induced acute lung injury mouse model, F. thunbergii Miq. and its component peimisine significantly alleviated lung injury and inflammation. Subsequent molecular docking validated peimisine’s binding affinity with critical targets (CASP3, MAPK14, ALB), supported by a Gene-Metabolite Interaction Network highlighting multi-targeted regulatory effects. These findings demonstrate that F. thunbergii Miq. mitigates pneumonia through modulation of glutamine metabolism, inflammatory pathways, and oxidative stress, providing a scientific foundation for its clinical application and future research.