Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis
Background: The current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. Methods: The docking between apigenin a...
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/24/8658 |
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| author | Faiq Amin Mahmoud A. A. Ibrahim Syed Rizwan-ul-Hasan Saima Khaliq Gamal A. Gabr Muhammad Asra Khan Peter A. Sidhom Prashant Tikmani Ahmed M. Shawky Saara Ahmad Syed Hani Abidi |
| author_facet | Faiq Amin Mahmoud A. A. Ibrahim Syed Rizwan-ul-Hasan Saima Khaliq Gamal A. Gabr Muhammad Asra Khan Peter A. Sidhom Prashant Tikmani Ahmed M. Shawky Saara Ahmad Syed Hani Abidi |
| author_sort | Faiq Amin |
| collection | DOAJ |
| description | Background: The current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. Methods: The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC), fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. Results: The binding affinity estimations identified the superior interacting capacity of apigenin over safranal for 5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability and absorbance. In the rodent model, there was a significant increase in the overall mobility time in the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety symptoms after treatment. Conclusions: Our analyses suggest apigenin and safranal as prospective medication options to treat depression and anxiety. |
| first_indexed | 2024-03-09T16:03:46Z |
| format | Article |
| id | doaj.art-f9ba7f2829f046e58ff1ede383dab5a1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:03:46Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f9ba7f2829f046e58ff1ede383dab5a12023-11-24T16:55:13ZengMDPI AGMolecules1420-30492022-12-012724865810.3390/molecules27248658Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo AnalysisFaiq Amin0Mahmoud A. A. Ibrahim1Syed Rizwan-ul-Hasan2Saima Khaliq3Gamal A. Gabr4Muhammad5Asra Khan6Peter A. Sidhom7Prashant Tikmani8Ahmed M. Shawky9Saara Ahmad10Syed Hani Abidi11Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, PakistanComputational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, EgyptDepartment of Computer Science, DHA Suffa University, Karachi 75500, PakistanDepartment of Biochemistry, Federal Urdu University of Arts, Science and Technology, Karachi 75300, PakistanDepartment of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Biochemistry, Federal Urdu University of Arts, Science and Technology, Karachi 75300, PakistanDepartment of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, PakistanDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, EgyptDepartment of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, PakistanScience and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, PakistanDepartment of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, PakistanBackground: The current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. Methods: The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC), fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. Results: The binding affinity estimations identified the superior interacting capacity of apigenin over safranal for 5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability and absorbance. In the rodent model, there was a significant increase in the overall mobility time in the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety symptoms after treatment. Conclusions: Our analyses suggest apigenin and safranal as prospective medication options to treat depression and anxiety.https://www.mdpi.com/1420-3049/27/24/8658depressionanxietynatural compoundsmolecular docking and dynamicsserotonin receptorsmurine model |
| spellingShingle | Faiq Amin Mahmoud A. A. Ibrahim Syed Rizwan-ul-Hasan Saima Khaliq Gamal A. Gabr Muhammad Asra Khan Peter A. Sidhom Prashant Tikmani Ahmed M. Shawky Saara Ahmad Syed Hani Abidi Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis Molecules depression anxiety natural compounds molecular docking and dynamics serotonin receptors murine model |
| title | Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis |
| title_full | Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis |
| title_fullStr | Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis |
| title_full_unstemmed | Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis |
| title_short | Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis |
| title_sort | interactions of apigenin and safranal with the 5ht1a and 5ht2a receptors and behavioral effects in depression and anxiety a molecular docking lipid mediated molecular dynamics and in vivo analysis |
| topic | depression anxiety natural compounds molecular docking and dynamics serotonin receptors murine model |
| url | https://www.mdpi.com/1420-3049/27/24/8658 |
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