Investigation of the Protective Effect of <i>Stemona</i> Alkaloids on Acute Lung Injury via LC–MS/MS‐Based Sphingolipid Metabolomic Profiling

The dried roots of S. tuberosa (known as "Baibu" in traditional Chinese medicine) have long been used for the treatment of pulmonary infections. Alkaloids are recognized as the principal bioactive constituents underlying their therapeutic effects. In this study, the alkaloids of S. tuberosa were annotated based on the UHPLC-MS/MS and an acute lung injury (ALI) model was established in mice by intratracheal instillation of LPS to evaluate the protective efficacy of Stemona alkaloid extracts and to explore their regulatory role in sphingolipid metabolism. Histopathological evaluation and ELISA assays demonstrated that the extract markedly alleviated pulmonary edema, reduced inflammatory cell infiltration, and decreased TNF-α, IL-6, IL-1β, MPO, and ROS levels. UHPLC-MS/MS-based sphingolipidomics analysis identified significant alterations in ceramide (Cer), sphingomyelin (SM), and lactosylceramide (LacCer) in the model group, all of which were reversed after alkaloid treatment. These findings suggest that Stemona alkaloids exert protective effects against LPS-induced ALI and restore sphingolipid homeostasis, thereby providing mechanistic insight into their traditional clinical efficacy.