Bioactivity-Guided Identification of Metabolites from Syzygium polycephalum with Antioxidant and α-Glucosidase Inhibitory Activities

Syzygium polycephalum (Miq.) Merr. & L.M. Perry is an underexplored species within the Syzygium genus, traditionally consumed for its edible fruit. However, the potential of its non-edible biomass as a source of bioactive metabolites remains poorly investigated. This study evaluated the antioxidant and α-glucosidase inhibitory activities of different parts of S. polycephalum and identified the metabolites associated with these activities using an LC-HRMS-guided approach. The ethanolic leaf extract demonstrated superior phenolic (457.89 ± 12.10 mg GAE/g) and flavonoid (11.08 ± 1.10 mg QE/g) contents with strong antioxidant (DPPH: 683.21 ± 24.54; FRAP: 1338.37 ± 7.04; CUPRAC: 771.91 ± 8.78 mg AEAC/g) and alpha-glucosidase inhibitory activities (52,145.16 ± 801.54 mg AEAGIC/g). LC–HRMS/MS identified four compounds, including chrysin and formononetin. Integrated in silico analyses revealed that chrysin consistently outperformed other metabolites, exhibiting optimal docking scores, favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and superior dynamic stability and binding affinity in molecular dynamics simulations. Collectively, these results position chrysin as the dominant bioactive driver and establish S. polycephalum leaf as a promising and sustainable source of dual-acting antioxidant and antidiabetic agents.