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

Amin, FaiqIbrahim, Mahmoud A. A.Rizwan-ul-Hasan, SyedKhaliq, SaimaGabr, Gamal A.Khan, AsraSidhom, Peter A.Tikmani, PrashantShawky, Ahmed M.Ahmad, SaaraAbidi, Syed Hani2023-06-272023-06-272022Amin, F., Ibrahim, M. a. A., Rizwan-Ul-Hasan, S., Khaliq, S., Gabr, G. A., Muhammad, N., Khan, A., Sidhom, P. A., Tikmani, P., Shawky, A., Ahmad, S., & Abidi, S. H. (2022). 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, 27(24), 8658. https://doi.org/10.3390/molecules27248658http://nur.nu.edu.kz/handle/123456789/7263The 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.enAttribution-NonCommercial-ShareAlike 3.0 United StatesType of access: Open Accessdepressionanxietynatural compoundsmolecular docking and dynamicsserotonin receptorsmurine modelINTERACTIONS 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 ANALYSISArticle