# Antioxidant Activity and Potential Cholesterol Modulating Effect of Punica granatum L. Peel Hydroethanolic Extract

**Authors:** Raja Chaaba, Amel Nakbi, Ilaria Rossi, Hanen Jrah, Zahra Amri, Nicola Ferri, Sonia Hammami, Stefano Dall'Acqua, Mohamed Hammami, Sounira Mehri

PMC · DOI: 10.1002/cbdv.202501668 · 2025-11-08

## TL;DR

Punica granatum peel extract shows strong antioxidant activity and may help lower cholesterol by affecting key proteins involved in lipid metabolism.

## Contribution

The study identifies specific phenolic compounds in P. granatum peel and their effect on PCSK9 and LDLR protein expression.

## Key findings

- PPE is rich in phenolic compounds like punicalin, pedunculagin I, and galloyl-HHDP-hexose.
- PPE upregulates PCSK9 and LDLR protein expression in cultured cells, similar to statins but less strongly.
- The extract exhibits strong antioxidant activity and potential cardioprotective effects.

## Abstract

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.

Punica granatum peel extract is rich in phenolic compounds, exhibits strong antioxidant activity, and modulates the expression of PCSK9 and LDL receptors. Collectively, these findings suggest a potential cardioprotective effect of the extract.

## Linked entities

- **Proteins:** PCSK9 (proprotein convertase subtilisin/kexin type 9), LDLR (low density lipoprotein receptor)
- **Chemicals:** punicalin (PubChem CID 5464368), pedunculagin I (PubChem CID 492391), galloyl-HHDP-hexose (PubChem CID 14428069)
- **Species:** Punica granatum (taxon 22663)

## Full-text entities

- **Diseases:** cardiovascular diseases (MESH:D002318)
- **Chemicals:** Cholesterol (MESH:D002784), punicalin (MESH:C115643), Punica granatum peel (-), pedunculagin I (MESH:C000606212), lipid (MESH:D008055)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12761359/full.md

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Source: https://tomesphere.com/paper/PMC12761359