Chemical Composition of the Phenolic Profile and Evaluation of Antimicrobial and Cytotoxic Activities of Moroccan Pomegranate (Punica granatum) Peel Extract

This study aims to deepen the understanding of the pharmacological properties of the aqueous extract derived from the peel of Punica granatum L., sourced from eastern Morocco. Chemical analysis using ultra-high-performance liquid chromatography (UHPLC) led to the identification of 30 compounds, mainly phenolic acids and flavonoids. The major constituents were quercetin (23.32%), gallic acid (12.85%), caffeic acid (12.44%), and hesperetin (12.11%). The antimicrobial activity of the extract was evaluated using the broth microdilution method, revealing strong efficacy against Gram-positive bacteria, particularly Bacillus cereus (MIC = 0.781 mg/mL) and Staphylococcus aureus (MIC = 1.56 mg/mL), while Escherichia coli exhibited higher resistance (MIC = 3.125 mg/mL). Cytotoxicity assessment showed greater inhibition of splenocytes (IC₅₀ = 708.7 ± 49.46 µg/mL) compared to myeloma P3 cell lines (IC₅₀ = 950.3 ± 43.8 µg/mL), suggesting potential selectivity. An in silico study was conducted to explore the pharmacokinetic and toxicological properties of the main compounds. Hesperetin and gallic acid were predicted to be non-toxic and exhibited strong binding affinities to antibacterial target proteins and to BCL-2, a key regulator of apoptosis. Hesperetin demonstrated more stable and diverse interactions with BCL-2, indicating superior potential as an inhibitor. These findings suggest that pomegranate peel extract may serve as a promising source of bioactive compounds for the development of new antimicrobial and anticancer agents.