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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1565628
This article is part of the Research TopicTranslational Potential of Novel Biomarkers and Molecular Targets in Lifestyle DisordersView all articles
The Effects of Ondansetron on Diabetes and High Fat Diet-Induced Liver Disease: A Critical Role for Protein Tyrosine Phosphatase 1B
Provisionally accepted
Fawad Naeem1*
Maryam Aqeel2
Muhammad Ammar Zahid3
Mustafeez Mujtaba Babar1
Fawad Shah2
Abdelali Agouni3
Sohaib Zafar Malik2- 1Shifa Tameer-e-Millat University, Islamabad, Pakistan
- 2Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Islamabad, Pakistan
- 3Qatar University, Doha, Qatar
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The escalating prevalence of diabetes and non-alcoholic fatty liver disease (NAFLD) has intensified the search for effective therapeutic interventions. The current study investigates the potential of ondansetron, an FDA-approved drug in conditions like nausea and vomiting, as a novel treatment option for these metabolic disorders using a multifaceted approach, encompassing computational analyses, in vitro enzyme inhibition assays, and in vivo experiments in a high-fat diet (HFD)-induced disease model in rats. Computational studies, including pharmacophore modelling, molecular docking, and molecular dynamics simulations, revealed ondansetron's strong binding affinity to the allosteric site of protein tyrosine phosphatase 1B (PTP1B), a key regulator of insulin and lipid homeostasis. The in vitro enzyme inhibition assay further confirmed ondansetron's ability to directly inhibit PTP1B. Animal experiments demonstrated ondansetron's anti-hyperglycemic effects, reducing blood glucose levels and improving insulin sensitivity in HFD-fed rats. The drug also exhibited hepatoprotective properties, mitigating liver damage and improving tissue architecture. Additionally, ondansetron's anti-inflammatory and antioxidant activities were evident in its ability to reduce pro-inflammatory markers and oxidative stress in the liver. These therapeutic effects position ondansetron as a promising candidate for further investigation in clinical settings for the treatment of diabetes and NAFLD and, hence, employing the drug repurposing approach for addressing the growing burden of metabolic diseases.
Keywords: Ondansetron, PTP1B, diabetes, high-fat diet-induced obesity, Non-alcoholic fatty liver disease
Received: 23 Jan 2025; Accepted: 18 Mar 2025.
Copyright: © 2025 Naeem, Aqeel, Zahid, Babar, Shah, Agouni and Malik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fawad Naeem, Shifa Tameer-e-Millat University, Islamabad, Pakistan
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