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The effects of ondansetron on diabetes and high-fat diet-induced liver disease: a critical role for protein tyrosine phosphatase 1B

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Argitaratua izan da:Frontiers in Pharmacology vol. 16 (Apr 2025), p. 1565628-1565644
Egile nagusia: Naeem, Fawad
Beste egile batzuk: Aqeel, Maryam, Muhammad Ammar Zahid, Mustafeez Mujtaba Babar, Fawad Ali Shah, Agouni, Abdelali, Sohaib Zafar Malik
Argitaratua:
Frontiers Media SA
Gaiak:
Food & Drug Administration > FDA
United Kingdom > UK
New York
United States > US
Diabetes
Insulin resistance
Hydrogen bonds
High fat diet
Binding sites
Fatty liver
Drug development
Blood levels
Computer applications
Metabolism
Inflammation
Liver diseases
Apoptosis
Metabolic disorders
Proteins
Protein-tyrosine-phosphatase
Therapeutic applications
Simulation
Phosphatase
Insulin
FDA approval
Oxidative stress
Glucose
Diabetes mellitus
Tumor necrosis factor-TNF
Ligands
Homeostasis
Allosteric properties
Enzymes
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Laburpena:IntroductionThe 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, a Food and Drug Administration (FDA)-approved drug for conditions like nausea and vomiting, as a novel treatment option for these metabolic disorders.MethodsA 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 were employed.ResultsComputational studies, including pharmacophore modeling, molecular docking, and molecular dynamics (MD) simulations, revealed the strong binding affinity of ondansetron 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 activity. Animal experiments demonstrated ondansetron’s antihyperglycemic 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.DiscussionThese therapeutic effects position ondansetron as a promising candidate for further investigation in clinical settings for the treatment of diabetes and NAFLD and, hence, support the use of the drug repurposing approach for addressing the growing burden of metabolic diseases.
ISSN:1663-9812
DOI:1565628
Baliabidea:Biological Science Database