Integrated nontargeted metabolomics and in silico analysis of bioactive compounds from five different parts of Aquilaria sinensis against ulcerative colitis

Aquilaria sinensis (Lour.) Gilg is the primary source of agarwood (known as “Chen-Xiang” in Chinese), a resinous wood widely used in traditional medicine for gastrointestinal disorders. However, the phytochemical diversity and therapeutic potential of different anatomical parts remain underexplored. This study integrated UPLC-Q-TOF-MSᴱ-based nontargeted metabolomics with multivariate statistical analysis, network pharmacology, and molecular docking to characterize the chemical profiles of five parts (leaves, stems, roots, shell, and agarwood) and predict their anti-ulcerative colitis (UC) mechanisms. A total of 124 components (27 chromone derivatives, 29 flavonoids, 36 terpenoids, 16 lignans, 7 simple phenolics, 5 benzophenones, 3 phenylpropanoids, and 1 alkaloid) were identified. Multivariate analysis revealed 28 differential metabolic markers that distinguished the five parts, with stems (12 marker compounds) and agarwood (8 marker compounds) showing the highest chemical specificity. Network pharmacology identified 139 common targets between these marker compounds and UC, with AKT1, TNF, IL6, STAT3, and BCL2 as core hubs. KEGG enrichment highlighted the PI3K-AKT, HIF-1, and T-cell receptor pathways. Molecular docking confirmed strong binding affinities, with (−)-aquisinenone G showing the highest affinity to AKT1 (−12.8 kcal/mol). Notably, four stem-derived compounds, 11-oxo-β-amyrin, (−)-aquisinenone G, justidin F, and wiktroemin, exhibited potent AKT1-targeting potential. These findings provide a chemical and mechanistic basis for the comprehensive utilization of A. sinensis parts and prioritize specific compounds for further in vivo validation.