Selective Recovery of Flavanone-Enriched Fractions from Glycyrrhiza Glabra Leaves by Supercritical CO2 Extraction with Neuroprotective Potential

Glycyrrhiza glabra leaves (GGL) are an underutilized by-product of the licorice supply chain and a valuable source of bioactive flavanones. In this study, supercritical CO2 fluid extraction (SFE-CO2) was optimized for the selective recovery of leaf-exudate flavanones (pinocembrin, licoflavanone, and glabranin). Response surface methodology combined with UHPLC–UV profiling enabled the identification of optimal conditions, yielding high-purity (31% flavanones), solvent-free, and ready-to-use enriched extracts. SFE-CO2 outperformed solvent-based liquid extraction in terms of selectivity and enrichment capacity. Path2Green assessment indicated an environmentally sustainable and scalable profile. The extract exhibited antioxidant and anti-aging effects in a yeast model of Parkinson’s disease (PD), extending lifespan and reducing oxidative stress. Pinocembrin, the most abundant flavanone, inhibited α-synuclein aggregation in vitro and ameliorated PD-related phenotypes in a Drosophila melanogaster model, improving locomotor performance and increasing cellular energy metabolism. These results support the sustainable valorization of GGL into flavanone-enriched extracts with potential nutraceutical applications for aging-related disorders.