Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 3 2026 09 30 Protodioscin Restores Ovarian Function and Suppresses p53–Bax/Bcl-2–Mediated Apoptosis in a Doxorubicin-Induced Model of Ovarian Toxicity 647 654 10.34172/apb.46593 EN Amoura M. Abou-El-Naga https://orcid.org/0000-0002-6369-5909 Aya M. Abd-Elhady Mohamed E. Abdraboh Yasmin M. Tag Maher Monir. Akl https://orcid.org/0000-0001-5480-1688 Journal Article 10.34172/apb.46593 2025 10 18 2026 05 07 Introduction: This study evaluated the protective effects of protodioscin against doxorubicin (DOX)-induced ovarian injury by examining its potential to modulate hormonal alterations and apoptosis-related pathways in a rat model. Methods: Forty female Wistar rats were randomized into four groups: control, protodioscin (10 mg/kg orally for 14 days), DOX (10 mg/kg intraperitoneally on Day 7), and DOX plus protodioscin. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and 17β-estradiol (E2) were quantified using enzyme-linked immunosorbent assay. Ovarian histopathology and immunohistochemistry were performed to evaluate tissue integrity and expression of p53, CDK4, and Survivin. Gene expression of Bax and Bcl-2 was assessed using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: DOX administration significantly reduced ovarian weight by 38.5% and uterine weight by 22.6% (P<0.01) compared with controls, accompanied by marked hormonal alterations, including increased FSH and decreased LH, AMH, and E2 levels. DOX also increased p53 and Bax expression and decreased Bcl-2 expression, resulting in an elevated Bax/Bcl-2 ratio. Co-treatment with protodioscin significantly attenuated these changes, partially restoring hormonal levels and modulating apoptosis-related markers. Protodioscin reduced p53 and Bax expression while increasing Bcl-2, CDK4, and Survivin levels, leading to a marked reduction in the Bax/Bcl-2 ratio (P<0.05). Conclusion: Protodioscin exerts a protective effect against DOX-induced ovarian injury, likely through modulation of hormonal disturbances and apoptosis-related pathways. However, these findings should be interpreted with caution due to the absence of estrous cycle synchronization and the use of an acute DOX model.