Purification With XAD-16 Resin Intensifies the Polyphenolic Composition, Antioxidant Potential, and Anti-obesity Properties of Apple Peel Extracts

Apple peel (AP) is a rich source of polyphenols with potential applications in functional food development. This study investigated the optimization of green ultrasound-assisted extraction of polyphenols from Red Prince apple peel using response surface methodology (RSM), evaluating the effects of ultrasound power, ethanol concentration, and solid-to-solvent ratio on extraction efficiency and polyphenol bioactivity. The optimal extraction conditions consisted of a 1:15 solid-to-solvent ratio, 500 W ultrasound power, and 50% ethanol. The crude extract (CE) was subsequently purified using XAD-16 resin. Purification increased total phenolic, anthocyanin, and tannin contents by 28-, 6-, and 19-fold, respectively. The main phenolic compounds in the purified extract (PE) were hyperoside (16.65 mg/g), procyanidin B2 (9.59 mg/g), and epicatechin (8.50 mg/g). Both CE (30–300 mg/L) and PE (1–10 mg/L) protected erythrocytes against AAPH-induced hemolysis. PE markedly reduced ROS generation at 10 mg/L; however, at lower concentrations (1–2 mg/L), ROS levels increased, suggesting a potential pro-oxidant effect. In 2D HepG2 cultures, the CE extract was non-cytotoxic at 5–300 μg/mL and reduced intracellular ROS production. In contrast, PE decreased HepG2 viability at 200–300 μg/mL and exhibited only a modest reduction in ROS generation at 5–100 μg/mL. In 3D HepG2 spheroids, both extracts decreased cell viability in a dose- and time-dependent manner and affected spheroid growth and structural integrity. Additionally, CE and PE showed dose-dependent inhibition of pancreatic lipase and HMG-CoA reductase, suggesting their potential to modulate obesity-related metabolic targets, with PE exhibiting stronger activity.