Ultrasound-assisted extraction of bioactive compounds from pomegranate peel and seed: A comprehensive review of key parameters and optimization strategies

Pomegranate (Punica granatum L.) peel and seeds are rich in phenolics, flavonoids, anthocyanins, ellagitannins, tannins, and punicic acid, which exhibit potent antioxidant, antimicrobial, anti-inflammatory, and anticancer properties. Conventional extraction methods, such as maceration, Soxhlet extraction, and hydrodistillation, are limited by excessive solvent and energy consumption, prolonged extraction times, and degradation of thermolabile compounds. Ultrasound-assisted extraction (UAE) has emerged as a sustainable and efficient alternative, utilizing acoustic cavitation to disrupt cell walls, enhance solvent penetration, and accelerate mass transfer. This review presents a comprehensive and UAE-specific synthesis of research on pomegranate peel and seed bioactives, focusing on the effect of key parameters ultrasonic power, frequency, extraction time, temperature, solvent system, solid-to-solvent ratio, and particle size on extraction efficiency and compound stability. Optimization strategies based on Response Surface Methodology, Box-Behnken Design, and Artificial Neural Networks are critically discussed to demonstrate their roles in maximizing yield and predicting extraction performance. Structural and spectroscopic studies confirming ultrasound-induced morphological disruption and molecular interactions are also summarized. This review uniquely synthesizes UAE-specific process parameters, optimization models, and structural characterization for both pomegranate peel and seed within a green valorization framework. Comparative analysis highlights the UAE superior performance over conventional and hybrid methods (microwave-, enzyme-, or deep eutectic solvent-assisted extractions). The review also identifies persisting challenges related to process scale-up, standardization of reporting metrics, and in vivo bioavailability assessment. Overall, this work provides an updated framework for improving extraction efficiency and supports the green valorization of pomegranate by-products into functional ingredients for food, nutraceutical, cosmetic, and pharmaceutical industries.