Oxidative stress mitigation by leaves of Dodonaea viscosa Jacq. flavonoid-rich extract confers protection against protein glycation, amyloid formation, and neurotoxic enzyme activity.

Metabolic and neurological disorders involve oxidative stress, protein glycation, and neurotoxic enzyme activity. Flavonoids, potent antioxidants, are widely used against chronic diseases and are abundant in the medicinal plant Dodonaea viscosa Jacq. (DV). A flavonoid-rich DV leaf extract was optimised by ultrasonic extraction, and its biochemical, metabolic, and neuroprotective effects were evaluated in vitro. The optimised extract (30 min sonication, 50 °C, 60% ethanol, 1:15 solid-solvent) was validated by LC-MS. It significantly inhibited glycation markers (fructosamine, carbonyls, and amyloid) in a BSA-fructose model (p < 0.001) while preserving thiols. DV extract also markedly inhibited monoamine oxidase-B, acetylcholinesterase, and butyrylcholinesterase (IC50: 70.82, 76.32, and 69.42 μg/mL; p < 0.001). In PC-12 and HEK293 cells, it showed low cytotoxicity (IC50: 161.9 and 182.4 μg/mL) and reduced ROS-positive cells (14.4% DCFDA, 17.31% MFI). These data support D. viscosa as a promising source of multifunctional flavonoids for metabolic and neurodegenerative therapy.