Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies
ABSTRACT 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 do...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70516 |
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| author | Md. Sakib Al Hasan Mohd Shahnawaz Khan Arusha Ayub Raihan Chowdhury Emon Mia Md. Shadin Md. Showkot Akbor Muhammad Torequl Islam Md. Shimul Bhuia |
| author_facet | Md. Sakib Al Hasan Mohd Shahnawaz Khan Arusha Ayub Raihan Chowdhury Emon Mia Md. Shadin Md. Showkot Akbor Muhammad Torequl Islam Md. Shimul Bhuia |
| author_sort | Md. Sakib Al Hasan |
| collection | DOAJ |
| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-72a2e36f34ec4be2909ccb5555a7dc7b |
| institution | Kabale University |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| series | Brain and Behavior |
| spelling | doaj-art-72a2e36f34ec4be2909ccb5555a7dc7b2025-08-20T03:48:26ZengWileyBrain and Behavior2162-32792025-05-01155n/an/a10.1002/brb3.70516Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico StudiesMd. Sakib Al Hasan0Mohd Shahnawaz Khan1Arusha Ayub2Raihan Chowdhury3Emon Mia4Md. Shadin5Md. Showkot Akbor6Muhammad Torequl Islam7Md. Shimul Bhuia8Department of PharmacyGoapalganj Science and Technology UniversityGopalganj BangladeshDepartment of BiochemistryKing Saud UniversityRiyadhSaudi ArabiaDepartment of Medicine, College of Health SciencesUniversity of GeorgiaGeorgiaUSADepartment of PharmacyGoapalganj Science and Technology UniversityGopalganj BangladeshDepartment of PharmacyGoapalganj Science and Technology UniversityGopalganj BangladeshDepartment of PharmacyGoapalganj Science and Technology UniversityGopalganj BangladeshDepartment of PharmacyGoapalganj Science and Technology UniversityGopalganj BangladeshPharmacy DisciplineKhulna UniversityKhulnaBangladeshDepartment of PharmacyGoapalganj Science and Technology UniversityGopalganj BangladeshABSTRACT 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.https://doi.org/10.1002/brb3.70516dopamine receptormemory‐enhancing effectmolecular interactionstangeretin |
| spellingShingle | Md. Sakib Al Hasan Mohd Shahnawaz Khan Arusha Ayub Raihan Chowdhury Emon Mia Md. Shadin Md. Showkot Akbor Muhammad Torequl Islam Md. Shimul Bhuia Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies Brain and Behavior dopamine receptor memory‐enhancing effect molecular interactions tangeretin |
| title | Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies |
| title_full | Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies |
| title_fullStr | Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies |
| title_full_unstemmed | Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies |
| title_short | Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies |
| title_sort | tangeretin improves the memory of swiss mice suggesting potential molecular interventions through animal behavior assessments and in silico studies |
| topic | dopamine receptor memory‐enhancing effect molecular interactions tangeretin |
| url | https://doi.org/10.1002/brb3.70516 |
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