Metabolic profiling and hypolipidemic effects of different medicinal parts of Sibiraea angustata: Functional metabolite identification and mechanistic insights via LC-MS/MS-based molecular networking and network pharmacology

Sibiraea angustata (Rehder) Hand.-Mazz. (SA) is a widely used edible and medicinal herb. We first applied UPLC-QTOF-MS/MS, UPLC-QQQ-MS/MS, feature-based molecular networking (FBMN), network pharmacology, molecular docking, and molecular dynamics (MD) simulation to compare the metabolic profiles of five medicinal parts (root (SR), stem (SS), leaf (SL), flower (SF), and cluster (SC)) of SA and explore its hypolipidemic mechanisms. A total of 123 metabolites were annotated, with phenolic acids and derivatives, as well as the biosynthesis of phenylpropanoids, identified as key differentially expressed biomarkers and pathways. The SL extract showed the strongest in vitro hypolipidemic effect, due to its high monoterpenoid content. Key bioactive compounds, such as Sibiskoside, and targets like STAT3, AKT1, and IL6, were identified. KEGG analysis linked SA's effects on Lipid and atherosclerosis, Pathways in cancer, and PI3K-Akt signaling pathways. Strong binding affinities between active compounds and their targets, suggesting their potential as targeted hypolipidemic agents. These findings provided valuable insights into SA's metabolite composition and hypolipidemic mechanisms. • Feature-based molecular networking, UPLC-MS/MS, network pharmacology, molecular docking, and dynamics simulation are important tools in metabolomics research and mechanism exploration. • Phenolic acids and derivatives, as well as the biosynthesis of phenylpropanoids, were identified as key differentially expressed biomarkers and metabolic pathways in different medicinal parts of Sibiraea angustata . • Leaf samples exhibited the most optimal in vitro hypolipidemic effect, due to their high levels and diversity of monoterpenoids. • Key bioactive compounds like sibiskoside, targets such as STAT3, and pathways including Lipid and atherosclerosis, were identified as potential targeted hypolipidemic agents and pathways.