Md. Sakib Al Hasan, Mohd Shahnawaz Khan, Arusha Ayub, Raihan Chowdhury, Emon Mia, Md. Shadin, Md. Showkot Akbor, Muhammad Torequl Islam, Md. Shimul Bhuia
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This study aims to evaluate the memory-enhancing effects of TAN in <i>Swiss</i> mice and explore its potential molecular interactions with the D<sub>2</sub> dopamine (DOP) receptor through in vivo behavioral assessments and in silico approaches.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p><i>Swiss</i> mice were administered TAN (10 and 20 mg/kg), DOP (22 mg/kg), and olanzapine (OLN) (2 mg/kg), alone and in combinations per orally (p.o.), followed by cognitive assessments using marble burying, dust removal, and trained swimming tests. In silico studies included molecular docking against the D<sub>2</sub> receptor (PDB: 6CM4), pharmacokinetics (SwissADME, pkCSM), and toxicity predictions (ProTox-3).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>TAN significantly (<i>p</i> < 0.05) improved cognitive functions, including memory, anxiety, and motor coordination, in a dose-dependent manner, with 20 mg/kg showing the most notable effect. The combination of TAN-10 with DOP-22 enhanced these benefits, whereas TAN-10 with OLN-2 reduced cognitive improvements. TAN-treated Swiss mice showed better performance in marble burying, dust removal, and trained swimming tests, indicating enhanced memory, problem-solving, and motor coordination. These results suggest TAN's potential in cognitive enhancement, particularly with DOP-22. No deaths were observed in any treatment group, and all treated animals exhibited normal physiological activity with no signs of acute toxicity. In silico studies revealed that TAN exhibited the strongest binding affinity (BA) (−6.6 kcal/mol) with the D<sub>2</sub> receptor, forming multiple hydrogen bonds (HBs), which indicates its potential mechanism for memory enhancement via dopaminergic modulation. Pharmacokinetic analyses also showed that TAN has favorable ADMET properties, including high gastrointestinal absorption, blood–brain barrier penetration, and low toxicity.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>These findings highlight TAN's potential as a promising therapeutic candidate for memory-related disorders, warranting further clinical exploration.</p>\n </section>\n </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70516","citationCount":"0","resultStr":"{\"title\":\"Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies\",\"authors\":\"Md. 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Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies
Introduction
Tangeretin (TAN), a polymethoxylated flavone from citrus peels, exhibits neuroprotective, anti-inflammatory, and antioxidant properties. This study aims to evaluate the memory-enhancing effects of TAN in Swiss mice and explore its potential molecular interactions with the D2 dopamine (DOP) receptor through in vivo behavioral assessments and in silico approaches.
Methods
Swiss mice were administered TAN (10 and 20 mg/kg), DOP (22 mg/kg), and olanzapine (OLN) (2 mg/kg), alone and in combinations per orally (p.o.), followed by cognitive assessments using marble burying, dust removal, and trained swimming tests. In silico studies included molecular docking against the D2 receptor (PDB: 6CM4), pharmacokinetics (SwissADME, pkCSM), and toxicity predictions (ProTox-3).
Results
TAN significantly (p < 0.05) improved cognitive functions, including memory, anxiety, and motor coordination, in a dose-dependent manner, with 20 mg/kg showing the most notable effect. The combination of TAN-10 with DOP-22 enhanced these benefits, whereas TAN-10 with OLN-2 reduced cognitive improvements. TAN-treated Swiss mice showed better performance in marble burying, dust removal, and trained swimming tests, indicating enhanced memory, problem-solving, and motor coordination. These results suggest TAN's potential in cognitive enhancement, particularly with DOP-22. No deaths were observed in any treatment group, and all treated animals exhibited normal physiological activity with no signs of acute toxicity. In silico studies revealed that TAN exhibited the strongest binding affinity (BA) (−6.6 kcal/mol) with the D2 receptor, forming multiple hydrogen bonds (HBs), which indicates its potential mechanism for memory enhancement via dopaminergic modulation. Pharmacokinetic analyses also showed that TAN has favorable ADMET properties, including high gastrointestinal absorption, blood–brain barrier penetration, and low toxicity.
Conclusion
These findings highlight TAN's potential as a promising therapeutic candidate for memory-related disorders, warranting further clinical exploration.
期刊介绍：
Brain and Behavior is supported by other journals published by Wiley, including a number of society-owned journals. The journals listed below support Brain and Behavior and participate in the Manuscript Transfer Program by referring articles of suitable quality and offering authors the option to have their paper, with any peer review reports, automatically transferred to Brain and Behavior.
* [Acta Psychiatrica Scandinavica](https://publons.com/journal/1366/acta-psychiatrica-scandinavica)
* [Addiction Biology](https://publons.com/journal/1523/addiction-biology)
* [Aggressive Behavior](https://publons.com/journal/3611/aggressive-behavior)
* [Brain Pathology](https://publons.com/journal/1787/brain-pathology)
* [Child: Care, Health and Development](https://publons.com/journal/6111/child-care-health-and-development)
* [Criminal Behaviour and Mental Health](https://publons.com/journal/3839/criminal-behaviour-and-mental-health)
* [Depression and Anxiety](https://publons.com/journal/1528/depression-and-anxiety)
* Developmental Neurobiology
* [Developmental Science](https://publons.com/journal/1069/developmental-science)
* [European Journal of Neuroscience](https://publons.com/journal/1441/european-journal-of-neuroscience)
* [Genes, Brain and Behavior](https://publons.com/journal/1635/genes-brain-and-behavior)
* [GLIA](https://publons.com/journal/1287/glia)
* [Hippocampus](https://publons.com/journal/1056/hippocampus)
* [Human Brain Mapping](https://publons.com/journal/500/human-brain-mapping)
* [Journal for the Theory of Social Behaviour](https://publons.com/journal/7330/journal-for-the-theory-of-social-behaviour)
* [Journal of Comparative Neurology](https://publons.com/journal/1306/journal-of-comparative-neurology)
* [Journal of Neuroimaging](https://publons.com/journal/6379/journal-of-neuroimaging)
* [Journal of Neuroscience Research](https://publons.com/journal/2778/journal-of-neuroscience-research)
* [Journal of Organizational Behavior](https://publons.com/journal/1123/journal-of-organizational-behavior)
* [Journal of the Peripheral Nervous System](https://publons.com/journal/3929/journal-of-the-peripheral-nervous-system)
* [Muscle & Nerve](https://publons.com/journal/4448/muscle-and-nerve)
* [Neural Pathology and Applied Neurobiology](https://publons.com/journal/2401/neuropathology-and-applied-neurobiology)
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