Comparative Evaluation of the Antioxidant Activities and Selective Cytotoxic Effects of Black-Peel Pomegranate (Punica granatum L.) Extracts from Three Native Iranian Cultivars

Document Type : Research Paper

Authors

1 Ph.D. Student in Department of Agricultural Biotechnology, Faculty of Agricultural Sciences, University of Guilan, Rasht, Iran

2 Associate Prof., Department of Agricultural Biotechnology, Faculty of Agricultural Sciences, University of Guilan, Rasht, Iran

3 Prof., Department of Agricultural Biotechnology, Faculty of Agricultural Sciences, University of Guilan, Rasht, Iran

4 Assistant Prof., Department of Animal Sciences, Faculty of Aagricultural Sciences, University of Guilan, Rasht, Guilan, Iran

5 Assistant Prof., Medicinal Plants and Drug Research Institute, Shahid Beheshti University, Tehran, Iran

6 Associate Prof., Department of Biological Sciences and Chemistry, College of Arts and Sciences, University of Nizwa, Nizwa, Sultanate of Oman

10.30473/cb.2025.75086.2013

Abstract

This study evaluated the antioxidant and anticancer activities of both crude and fractionated (aqueous and ethyl acetate) extracts derived from black peel pomegranate fruits of three Iranian cultivars: Yazd, Saveh, and Esfahan. Extracts were obtained through sonication in a hydroalcoholic solvent, followed by liquid–liquid partitioning. Antioxidant capacity was assessed using the ABTS assay, while cytotoxic effects were measured via the MTT assay in two human breast cancer cell lines (MCF-7 and MDA-MB-231), along with normal HUVEC cells to assess selectivity. The ethyl acetate fraction of the Yazdi cultivar exhibited the highest antioxidant activity, achieving over 90% inhibition of ABTS⁺ radicals. It also induced significant, dose-dependent cytotoxicity in both cancer cell lines, with negligible effects on normal cells, indicating promising selectivity. To explore the mechanism of action, qRT-PCR was used to evaluate the expression of pro-apoptotic genes. Treatment with the Yazdi extract resulted in a substantial upregulation of BAX (12-fold) and TP53 (13-fold), suggesting activation of the intrinsic apoptotic pathway. The notable bioactivity observed in the Yazdi extract may be attributed to its rich phytochemical profile, potentially enhanced by the region’s arid climate, which is known to promote the biosynthesis of secondary metabolites. These findings highlight the potential of black peel pomegranate, particularly the Yazdi cultivar, as a natural, safe, and effective candidate for adjunctive breast cancer therapy. Additionally, the valorization of agricultural byproducts such as pomegranate peel represents a sustainable and cost-effective strategy in natural product-based drug discovery.

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References

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