Development of Sustainable Extraction Processes for the Recovery of Antioxidants from Punica granatum L. Peel

Background: Pomegranate peel, a major by-product of the food industry, represents an underexploited source of valuable bioactive compounds. In the framework of a circular economy approach, this study aimed to develop a sustainable and solvent-free extraction strategy based on Saccharomyces cerevisiae fermentation for the recovery of antioxidant and antimicrobial phytochemicals from pomegranate peel waste. Methods: Pomegranate peel was subjected to fermentation for 18, 24, 48, and 72 h, and the resulting extracts (YE_18h, YE_24h, YE_48h, and YE_72h), together with a conventionally obtained chemical extract (CE), were evaluated for their antioxidant activity. Based on its superior antioxidant activity, the extract obtained after 48 h of fermentation (YE_48h) was selected for ellagic acid quantification by HPLC and characterization by UHPLC-HRMS (Ultra-High-Performance Liquid Chromatography coupled to High-Resolution Mass Spectrometry). Antibacterial activity of YE_48h, in comparison with CE, was assessed against six Gram-positive and Gram-negative bacterial strains. Results: Among the fermented samples, the extract obtained after 48 h of fermentation (YE_48h) exhibited the highest antioxidant activity, showing an IC50 value lower than that of a conventional chemical extract. Quantitative HPLC analysis revealed a remarkable enhancement in ellagic acid content, with YE_48h containing approximately 18-fold higher levels of ellagic acid than the conventional chemical extraction. UHPLC-HRMS fingerprinting further demonstrated the presence of additional bioactive phenolic compounds, including punicalagin isomers I and II and pedunculagin isomer I, which are known for their antioxidant and antimicrobial properties. The antibacterial assay demonstrated that fermentation modulated the antimicrobial profile of the extracts in a strain-dependent manner. Conclusions: S. cerevisiae-mediated fermentation is an efficient and environmentally friendly approach for the valorization of pomegranate peel by-products, enhancing the release of bioactive compounds while generating extracts with promising antioxidant and selective antibacterial properties.