Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways
Abstract Anxiety is a natural response to stress, characterized by feelings of worry, fear, or unease. The current research was conducted to investigate the anxiolytic effect of indirubin (IND) in different behavioral paradigms in Swiss albino mice. To observe the animal's behavioural response...
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Wiley-VCH
2025-02-01
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| Series: | ChemistryOpen |
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| Online Access: | https://doi.org/10.1002/open.202400290 |
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| author | Ishrat Jahan Disha Rubel Hasan Md. Shimul Bhuia Siddique Akber Ansari Irfan Aamer Ansari Muhammad Torequl Islam |
| author_facet | Ishrat Jahan Disha Rubel Hasan Md. Shimul Bhuia Siddique Akber Ansari Irfan Aamer Ansari Muhammad Torequl Islam |
| author_sort | Ishrat Jahan Disha |
| collection | DOAJ |
| description | Abstract Anxiety is a natural response to stress, characterized by feelings of worry, fear, or unease. The current research was conducted to investigate the anxiolytic effect of indirubin (IND) in different behavioral paradigms in Swiss albino mice. To observe the animal's behavioural response to assess anxiolytic activity, different tests were performed, such as the open‐field (square cross, grooming, and rearing), swing, dark‐light, and hole cross tests. The experimental mice were administered IND (5 and 10 mg/kg, p.o.), where diazepam (DZP) and vehicle were used as positive and negative controls, respectively. In addition, a combination treatment (DZP+IND‐10) was provided to the animals to determine the modulatory effect of IND on DZP. Molecular docking approach was also conducted to determine the binding energy of IND with the GABAA receptor (α2 and α3 subunits) and pharmacokinetics were also estimated. The findings revealed that IND dose‐dependently significantly (p<0.05) reduced the animal's movement exerting calming behavior like DZP. IND also demonstrated the highest docking score (−7.7 kcal/mol) against the α3 subunit, while DZP showed a lower docking value (−6.4 kcal/mol) than IND. The ADMET analysis revealed that IND has proper drug‐likeness and pharmacokinetic characteristics. In conclusion, IND exerted anxiolytic effects through GABAergic Pathways. |
| format | Article |
| id | doaj-art-9bd53330a68b41279a4357f9c4d65ce5 |
| institution | Kabale University |
| issn | 2191-1363 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley-VCH |
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| series | ChemistryOpen |
| spelling | doaj-art-9bd53330a68b41279a4357f9c4d65ce52025-08-20T03:49:37ZengWiley-VCHChemistryOpen2191-13632025-02-01142n/an/a10.1002/open.202400290Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic PathwaysIshrat Jahan Disha0Rubel Hasan1Md. Shimul Bhuia2Siddique Akber Ansari3Irfan Aamer Ansari4Muhammad Torequl Islam5Biochemistry and Molecular Biology Bangabandhu Sheikh Mujibur Rahman Science and Technology University Gopalganj 8100 BangladeshBioinformatics and Drug Innovation Laboratory BioLuster Research Center Ltd. Gopalganj, Dhaka 8100 BangladeshBioinformatics and Drug Innovation Laboratory BioLuster Research Center Ltd. Gopalganj, Dhaka 8100 BangladeshDepartment of Pharmaceutical Chemistry College of Pharmacy King Saud University Riyadh 11451 Saudi ArabiaDepartment of Drug Science and Technology University of Turin Turin 10124 ItalyDepartment of Pharmacy Bangabandhu Sheikh Mujibur Rahman Science and Technology University Gopalganj 8100 BangladeshAbstract Anxiety is a natural response to stress, characterized by feelings of worry, fear, or unease. The current research was conducted to investigate the anxiolytic effect of indirubin (IND) in different behavioral paradigms in Swiss albino mice. To observe the animal's behavioural response to assess anxiolytic activity, different tests were performed, such as the open‐field (square cross, grooming, and rearing), swing, dark‐light, and hole cross tests. The experimental mice were administered IND (5 and 10 mg/kg, p.o.), where diazepam (DZP) and vehicle were used as positive and negative controls, respectively. In addition, a combination treatment (DZP+IND‐10) was provided to the animals to determine the modulatory effect of IND on DZP. Molecular docking approach was also conducted to determine the binding energy of IND with the GABAA receptor (α2 and α3 subunits) and pharmacokinetics were also estimated. The findings revealed that IND dose‐dependently significantly (p<0.05) reduced the animal's movement exerting calming behavior like DZP. IND also demonstrated the highest docking score (−7.7 kcal/mol) against the α3 subunit, while DZP showed a lower docking value (−6.4 kcal/mol) than IND. The ADMET analysis revealed that IND has proper drug‐likeness and pharmacokinetic characteristics. In conclusion, IND exerted anxiolytic effects through GABAergic Pathways.https://doi.org/10.1002/open.202400290AnxietyIndirubinDiazepamMolecular dockingin vivo study |
| spellingShingle | Ishrat Jahan Disha Rubel Hasan Md. Shimul Bhuia Siddique Akber Ansari Irfan Aamer Ansari Muhammad Torequl Islam Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways ChemistryOpen Anxiety Indirubin Diazepam Molecular docking in vivo study |
| title | Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways |
| title_full | Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways |
| title_fullStr | Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways |
| title_full_unstemmed | Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways |
| title_short | Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways |
| title_sort | anxiolytic efficacy of indirubin in vivo approach along with receptor binding profiling and molecular interaction with gabaergic pathways |
| topic | Anxiety Indirubin Diazepam Molecular docking in vivo study |
| url | https://doi.org/10.1002/open.202400290 |
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