Abstract
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.
Highlights
- Ultrasound-assisted extraction enhances bioactive yield from pomegranate peel and seed.
- Key UAE parameters and optimization models (RSM, BBD, ANN) are critically reviewed.
- Comparative analysis shows UAE outperforms conventional extraction methods.
- The review integrates mechanistic, modeling, and industrial applicability aspects.
- Supports green valorization of pomegranate by-products for food and nutraceutical use.
Introduction
Pomegranate (Punica granatum L.), a member of the Punicaceae family, is a highly valued fruit native to Central Asia and cultivated in arid and semi-arid regions, including Iran, India, Mediterranean countries, and Brazil [1], [2], [3], [4]. Globally, over 500 cultivars exist, with fruit productivity reaching up to 6000 kg/ha under optimal conditions [1]. The fruit comprises approximately 38–50 % juice, 39–53 % peel, and 8–12 % seeds, generating substantial by-product waste during processing [1], [2], [5]. These by-products, especially peels and seeds, are rich in bioactive compounds, including phenolics (flavonoids, tannins, anthocyanins, ellagitannins), vitamins, minerals, sterols, dietary fibers, and fatty acids, exhibiting strong antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activities [6], [7], [8], [9]. Peel extracts show higher phenolic and flavonoid content compared to seeds, while both fractions offer significant potential for food, pharmaceutical, and nutraceutical applications [10].Table 1.Table 2.
Conventional extraction techniques, such as maceration, Soxhlet, hydrodistillation, and steam distillation, have been widely used to recover pomegranate bioactive [11], [12]. However, these methods are associated with long extraction times, high solvent consumption, thermal degradation of sensitive compounds, and environmental concerns. For example, hydrodistillation can consume up to 50 % more energy than advanced techniques, while Soxhlet extraction often requires 6–8 h to achieve moderate yields of phenolics and flavonoids [13]. These limitations highlight the need for more efficient and sustainable extraction approaches.
Ultrasound-Assisted Extraction (UAE) has emerged as a promising green technology, operating at frequencies between 20 kHz and 10 MHz, which induces cavitation, microjet formation, and particle breakdown, enhancing mass and heat transfer [14], [15], [16], [17]. UAE reduces extraction time by 40–60 %, decreases solvent consumption, preserves thermolabile compounds, and improves overall yield compared to conventional methods [13], [14]. UAE has demonstrated significantly higher recovery of phenolics, flavonoids, and anthocyanins from matrices such as pomegranate peel and seeds, often doubling yields relative to maceration or Soxhlet extraction [16].

Optimization of UAE parameters, including solvent type, solid-to-solvent ratio, ultrasonic power and frequency, temperature, particle size, and extraction time, is critical for maximizing bioactive recovery. Response surface methodology (RSM) is widely employed to identify optimal conditions while minimizing experimental trials and ensuring process efficiency [13], [14]. Despite numerous studies on UAE for various fruits and pomegranate, most reviews focus either on multiple fruits or all extraction techniques for pomegranate [1], [15], leaving a research gap in comprehensive reviews dedicated specifically to UAE optimization for pomegranate peel and seed bioactives.
The novelty of this review lies in its dedicated and comparative analysis of ultrasound-assisted extraction (UAE) parameters and optimization models for both pomegranate peel and seed. While previous reviews have broadly discussed various extraction methods or multiple fruit matrices, none have systematically compiled and analyzed UAE-specific studies emphasizing optimization, modeling approaches (RSM, BBD, ANN), and mechanistic–structural correlations. This review therefore provides the first integrated perspective that connects extraction parameters, modeling strategies, and industrial applicability to promote sustainable valorization of pomegranate by-products.
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Fatima Shehzadi, Muhammad Shoaib, Salman Munir, Gholamreza Abdi, Ultrasound-assisted extraction of bioactive compounds from pomegranate peel and seed: A comprehensive review of key parameters and optimization strategies, Ultrasonics Sonochemistry, 2025, 107722, ISSN 1350-4177, https://doi.org/10.1016/j.ultsonch.2025.107722.
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