Acoustic Cavitation-Driven Extraction of Ginger Phytochemicals: Modeling, Optimization and Bioactivity Evaluation.

Ultrasound-assisted extraction (UAE) is increasingly recognized as an effective process intensification strategy for phytochemical recovery; however, its optimization is often treated empirically, with limited mechanistic insight into solvent-cavitation interactions. In this study, a mechanistically informed and statistically optimized UAE approach was developed for ginger rhizome using environmentally benign ethanol-water solvent systems. A Box-Behnken design was employed to simultaneously evaluate the effects of ginger-to-solvent ratio, solvent composition, and extraction time on extraction yield, antioxidant activity (DPPH, ABTS, Phenanthroline, and CUPRAC assays), total phenolic content (TPC), and flavonol content (FC). The developed response surface models exhibited strong predictive performance, yielding an optimized extraction yield of 33.22%. Notably, solvent composition emerged as the dominant factor, with water-rich systems enhancing oil yield through intensified cavitation and matrix hydration effects, rather than solubility-driven mechanisms alone. Under optimized conditions, antioxidant activities of 27.06, 4.42, 3.59, and 4.70 µg/mL were obtained, alongside TPC and FC values of 79.67 mg GAE/g and 3.38 mg QE/g, respectively. GC-Q-TOF-MS analysis of extracts obtained with 0%, 50%, and 100% ethanol identified 11 major phenolic compounds, revealing solvent-dependent selectivity toward key bioactives. A direct comparison with Soxhlet extraction, optimized using the same RSM framework, confirmed that UAE significantly improves extraction efficiency and bioactivity retention while reducing extraction time and solvent consumption. Overall, this work provides both mechanistic understanding and practical optimization guidelines, supporting UAE as a scalable and sustainable extraction platform for food, pharmaceutical, and cosmetic applications.