Identification of Punicalagin as a Key Bioactive Compound Responsible for the Antimicrobial Properties of <i>Punica granatum</i> L. Peel Extract against <i>Staphylococcus aureus</i>

This study highlights the potential of <i>Punica granatum</i> (pomegranate) peel extract (PPE) as a natural antimicrobial alternative to synthetic chemicals. Pomegranate peels, typically considered a byproduct of fruit processing, contain bioactive compounds such as polyphenols, flavonoids, and tannins. This research explored the antimicrobial efficacy of these phytochemicals against <i>Staphylococcus aureus</i> using a bioassay-guided fractionation approach to identify key bioactive components. While evaluating antimicrobial efficacy is critical, it is equally important to ensure safety for human use. Therefore, we assessed the cytotoxicity of punicalagins α and β on human keratinocytes to determine their biocompatibility and potential for safe application in food or therapeutic settings. The antibacterial activity of PPE was then evaluated using different food models. Punicalagins α and β were identified as individual compounds, and their pure reference forms showed a minimum inhibitory concentration (MIC) of 16 μg/mL. None of the tested fractions exhibited significant cytotoxicity to human keratinocytes (HaCaTs) (IC₅₀ > 128 μg/mL). A significant reduction of up to 0.8-fold in bacterial cell counts was observed after PPE incorporation into tested food models. This research underscores the importance of exploring sustainable antimicrobial solutions derived from food industry byproducts as alternatives to synthetic antibiotics.