Polyphenol-Rich Extracts from Pomegranate Peels and Arils: Comparative Screening of Extraction Conditions, Phytochemical Characterization and Bioactivity in Breast Cancer Cell Models

The pomegranate (Punica granatum L.) is recognized for its pharmacological properties and traditional use in herbal medicine. While most studies have focused on the edible parts of the fruit, there is growing interest in the peel, a food by-product rich in bioactive compounds. This study aimed to optimize the extraction conditions of these compounds from ripe and unripe pomegranate peels and compared the results with those obtained from arils at the same maturity stage. Different solvents and extraction conditions, including room temperature, high-temperature, and ultrasound-assisted extraction, were evaluated in terms of extraction yield and phytochemical composition. Peel extracts showed significantly higher extraction yields and polyphenol contents than aril extracts. HPLC-UV/MS analysis identified punicalagin as the predominant compound, with marked differences between peels and arils and maturity stages. Antioxidant capacity revealed a strong anti-oxidant potential of peel-derived extracts. Selected extracts were further evaluated in cellular models to assess their antiproliferative activity against breast cancer. Peel extracts exhibited significant antiproliferative effects and provided cytoprotection against hydrogen peroxide-induced oxidative stress. These results support the valorization of pomegranate peel as a source of food-derived bioactive compounds and provide insight into their cellular effects, highlighting their potential application in functional foods and nutraceuticals.