Sustainable ultrasound-assisted extraction of Miliusa velutina stem bark: optimization, in vitro-in silico anti-metabolic syndrome evaluation, and life cycle assessment

• Optimized green extraction enhanced polyphenol yield from Miliusa velutina stem bark. • Life cycle assessment demonstrated sustainable extraction–to–bioactivity workflow. • Extract exhibited broad anti-metabolic syndrome activities in vitro . • HPLC identified chlorogenic acid, caffeic acid, hesperidin, rutin, quercetin. • Docking confirmed compound–target interactions relevant to metabolic syndrome. Metabolic syndrome (MetS) is associated with oxidative stress, lipid-glucose dysregulation, and chronic inflammation. Miliusa velutina (Annonaceae), a Southeast Asian plant, remains largely unexplored for its biological potential. This study developed a sustainable ultrasound-assisted extraction process to obtain a polyphenol- and flavonoid-rich extract from M. velutina stem bark and evaluated its MetS-related activities in vitro and in silico . The extraction process was optimal using response surface methodology. Optimal conditions (64 °C, 24 min, 68% ethanol, solvent-to-solid ratio of 1:21) yielded total polyphenol and flavonoid contents of 266.69 mg GAE/g and 207.75 mg QE/g. The extract exhibited strong antioxidant (IC 50 = 1.34 ± 0.03–73.80 ± 0.94 µg/mL), anti-inflammatory (IC 50 = 5.80 ± 0.04–9.55 ± 0.23 µg/mL), anti-cholesterol, enzyme inhibitory, and antibacterial activities. HPLC identified chlorogenic acid, caffeic acid, rutin, hesperidin, and quercetin. Docking analysis showed that quercetin had the highest binding affinity toward MetS-related enzymes. A life cycle assessment confirmed low environmental impact. Overall, this eco-efficient process yields a bioactive extract with promising anti-MetS potential.