Antioxidant Activity and Potential Cholesterol Modulating Effect of <i>Punica granatum</i> L. Peel Hydroethanolic Extract

Lipoprotein metabolism is regulated by several key proteins, notably proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR). Punica granatum peel extract has been reported to exhibit lipid-lowering properties; however, the underlying mechanisms of its action on lipid metabolism remain insufficiently characterized. In this study, the hydroethanolic extract of P. granatum peel (PPE) was found to be rich in phenolic compounds and exhibited strong antioxidant activity. Characterization by liquid chromatography coupled with diode array and multiple-stage mass spectrometry (LC-DAD-MSⁿ) identified punicalin, pedunculagin I, and galloyl-HHDP-hexose as the main constituents. Similar to statin treatment, PPE exposure significantly upregulated PCSK9 and LDLR protein expression in cultured cells compared to untreated controls, though the effect was less pronounced than that observed with statins. These findings suggest that phenolic-rich PPE may serve as a promising natural source for the development of therapeutic agents aimed at preventing cardiovascular diseases.