Antioxidant efficacy of Cotoneaster nummularius in phenylhydrazine-induced hyperbilirubinemia: A rat model study

Valipour, Faezeh; Safipour Afshar, Akbar; Azadbakht, Mohammad; Mohammadi, Hamidreza; Zhiani, Rahele

doi:10.22038/ajp.2025.26368

Antioxidant efficacy of Cotoneaster nummularius in phenylhydrazine-induced hyperbilirubinemia: A rat model study

Articles in Press

Document Type : Original Research Article

Authors

¹ Department of Biology, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran

² Department of Pharmacognosy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

³ Medicinal Plants Research Center, Mazandaran University of Medical Sciences, Sari, Iran

⁴ Department of Chemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran

10.22038/ajp.2025.26368

Abstract

Objective: This study investigated the hepatoprotective effects of Cotoneaster nummularius manna extract (CNE) against phenylhydrazine (PHZ)-induced hyperbilirubinemia and oxidative stress in a neonatal rat model.
Materials and Methods: Fifty neonatal Wistar rats (2 weeks old) were divided into five groups (n=10): a control group, a PHZ-only group, and three PHZ-treated groups receiving CNE (1, 2.5, and 5 mg/kg, orally, thrice daily for 10 days). PHZ was used to induce hemolysis and hyperbilirubinemia. Markers of liver function, oxidative stress, and antioxidant capacity were analyzed, alongside β-glucuronidase activity.
Results: CNE significantly mitigated PHZ-induced hyperbilirubinemia by reducing serum bilirubin levels and dose-dependently decreasing oxidative stress markers, including reactive oxygene species ROS, malondialdehyde (MDA), and protein carbonylation. It also restored glutathione (GSH) levels and total antioxidant capacity. The highest CNE dose (5 mg/kg) demonstrated the most pronounced effects. Furthermore, CNE inhibited β-glucuronidase activity, contributing to its hepatoprotective action. Hierarchical clustering and heatmap analyses corroborated the dose-dependent antioxidant and hepatoprotective properties of CNE.
Conclusion: These findings highlight the hepatoprotective potential of C. nummularius extract in reducing oxidative stress and hyperbilirubinemia. CNE dose-dependent effects, particularly at 5 mg/kg, suggest its promise as a therapeutic agent for neonatal liver dysfunction and oxidative damage. Further clinical studies are warranted to explore its potential applications in managing liver disorders.

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