Sargassum polycystum as natural source of antioxidant and antidiabetic compounds: a solvent-driven metabolomic profiling study

The increasing global demand for innovative natural therapeutics against oxidative stress and metabolic disorders has spotlighted marine algae as rich reservoirs of bioactive compounds. This pioneering study systematically investigates how extraction solvents and geographical origin can modulate the metabolomic landscape and bioactivity of Sargassum polycystum harvested from Indonesia's West Nusa Tenggara. Employing advanced UHPLC-HRMS metabolomics combined with antioxidant and antidiabetic assays, it has been possible to delineate the distinct phytochemical fingerprints shaped by acetone, methanol, and ethanol solvents from samples collected at Saleh Bay (Dompu) and Pulau Ngali Beach (Sumbawa). Seventeen signature metabolites were identified, prominently featuring the bioactive sugar alcohol D-(−)-mannitol, which underpins significant pharmacological effects. Remarkably, acetone extracts from Saleh Bay (SAD) exhibited superior phenolic and flavonoid content, correlating with potent antioxidant activities (DPPH IC50 = 1.82 mg/mL; ABTS IC50 = 2.38 mg/mL; FRAP 0.537 mmol Fe(II)/mL). Methanol and ethanol extracts showed robust α-glucosidase inhibition (∼81 %), while SAD extracts also excelled in α-amylase inhibition, highlighting a multifaceted antidiabetic potential. Integrative network pharmacology and molecular docking pinpointed key molecular targets (PPARA, MGAM, CYP19A1) and identified metabolites (indicated as C6 and C9) with high binding affinities to DPP4, PPARG, and NtMGAM, rivaling acarbose's efficacy. Favorable ADMET profiles of compounds such as D-(−)-mannitol and DL-malic acid further underscore their therapeutic promise. This study not only elucidates how extraction solvents and geographic provenance dynamically influence the bioactivity of S. polycystum but also pioneers its repositioning as a versatile marine candidate for natural antioxidant and antidiabetic drug discovery.