Abstract
Nephrolithiasis (kidney stone) is a global health concern with multifactorial origins, including genetic, environmental, dietary, and metabolic factors. This study investigates the therapeutic potential of Annona muricata (AM) leaf extract in mitigating nephrolithiasis-induced electrolyte imbalance, antioxidant depletion, and histopathological alterations in an ethylene glycol (EG)-challenged rat model by modulating Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities. Twenty-five male rats were randomly assigned to five experimental groups: 0.75% v/v ethylene glycol in drinking water for 28 days in the other groups, except the control (NC) group. The control (NC) and ethylene glycol-induced (EG) groups received distilled water, while other treatment groups were administered Zyloric (2 mg/kg/day), low-dose AM (200 mg/kg/day; EG + AML), and high-dose AM (800 mg/kg/day; EG + AMH) for 21 days. EG-induced disturbances in magnesium, sodium, potassium, chloride and calcium concentrations were effectively counteracted by both AM doses (200 mg/kg and 800 mg/kg/day) and Zyloric, with restorative effects on calcium levels of 8.02%, 18.18%, and 8.53%, and on magnesium levels of 12.77%, 25.24%, and 22.44%, respectively. Our findings suggest that AM exerts nephro-restorative effects by modulating electrolyte balance, ameliorating nephrolithiasis-induced histopathological changes, and enhancing antioxidant defences, as well as Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities. These results showed the potential of AM as a therapeutic candidate for kidney stone management and related renal dysfunctions. Conclusively, AM exhibited therapeutic potential against ethylene glycol (Nephrolithiasis)-induced electrolyte imbalance, antioxidant depletion, and histopathological changes.
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We gratefully recognise the contributions made by the study team and the entire laboratory staff of the Department of Biochemistry, Crescent University, Abeokuta.
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This is SA PhD research under the supervision of LA, OL, and OA, while OA collaborated and assisted with histology.
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All animal procedures and handling complied with established ethical and regulatory guidelines, including: The National Research Council’s Guide for the Care and Use of Laboratory Animals, which provides fundamental principles for the ethical treatment of experimental animals, and the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines as outlined by Percie et al., 2020, ensuring transparency and reproducibility in animal research. Ethical approval was granted by the Crescent University Research Ethics Committee, with the research protocols officially sanctioned under reference CRESCENT/CS/BCH/PG/S41512005.
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Rahman, S.A., Sulaimon, L.A., Arogundade, O.L. et al. Therapeutic efficacy of Annona muricata in counteracting nephrolithiasis-induced electrolyte imbalance and antioxidant disruption in ethylene glycol-treated rats. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35535-0
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DOI: https://doi.org/10.1038/s41598-026-35535-0
