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

**Authors:** Faezeh Valipour, Akbar Safipour Afshar, Mohammad Azadbakht, Hamidreza Mohammadi, Rahele Zhiani

PMC · DOI: 10.22038/ajp.2025.26368 · 2026-01-01

## TL;DR

This study shows that Cotoneaster nummularius extract can protect the liver and reduce oxidative stress in neonatal rats with hyperbilirubinemia.

## Contribution

The study demonstrates the dose-dependent hepatoprotective and antioxidant effects of Cotoneaster nummularius extract in a neonatal rat model of hyperbilirubinemia.

## Key findings

- CNE significantly reduced serum bilirubin levels and oxidative stress markers in a dose-dependent manner.
- The highest CNE dose (5 mg/kg) showed the most pronounced hepatoprotective effects.
- CNE inhibited β-glucuronidase activity, contributing to its liver-protective action.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Chemicals:** phenylhydrazine (PubChem CID 7516), glutathione (PubChem CID 124886), malondialdehyde (PubChem CID 10964)
- **Diseases:** hyperbilirubinemia (MONDO:0002408)

## Full-text entities

- **Genes:** Gusb (glucuronidase, beta) [NCBI Gene 24434] {aka Ac2-223, Gus-s}
- **Diseases:** liver disorders (MESH:D017093), hyperbilirubinemia (MESH:D006932), hemolysis (MESH:D006461)
- **Chemicals:** bilirubin (MESH:D001663), MDA (MESH:D008315), PHZ (MESH:C030299), GSH (MESH:D005978), C. nummularius extract (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Cotoneaster nummularius (species) [taxon 1804980]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12872067/full.md

---
Source: https://tomesphere.com/paper/PMC12872067