From Metabolome to Molecule: Discovery of Bioactive Small-Molecule Drug Candidates from Cupressus torulosa D. Don

Cupressus torulosa D. Don is an underexplored Himalayan conifer with potential as a source of bioactive natural products and a history of ethnopharmacological use for inflammatory conditions. This study integrates metabolomics, pharmacological evaluation, and molecular docking to identify and prioritize bioactive small molecules from C. torulosa needles. 25% methanolic needle extracts were subjected to LC-QTOF-MS/UPLC-QTOF-MS profiling and chemometric analysis to characterize metabolite diversity and identify potentially important constituents. The extracts were evaluated in vitro for antioxidant, α-amylase/α-glucosidase inhibitory and albumin-denaturation activities, and in vivo for anti-inflammatory and antidiabetic effects using paw-edema and streptozotocin-induced models, respectively. Based on their occurrence, bioactivity and pharmacological relevance, amentoflavone and fraxin were selected for molecular docking studies against therapeutically relevant targets, including α-amylase, α-glucosidase, COX-2 and 5-LOX. The integrated approach revealed diverse phenolic compounds, flavonoids, terpenoids and other metabolites with promising biological activities. These findings demonstrate the potential of C. torulosa as a source of natural-product-derived bioactive molecules and provide a metabolome-to-molecule framework for lead prioritization and future drug-discovery studies.