Assessment of Sedative Activity of Protodioscin: In Vivo Approach Along With Receptor Binding Affinity and Molecular Interaction With GABAergic System
Rokibul Islam Chowdhury, Shoyaeb Ahammed, Raihan Chowdhury, Salehin Sheikh, Shadma Wahab, Ayesha Siddiqua, Faisal H. Altemani, Md. Torequl IslamABSTRACT
A frequent sleep issue called insomnia can lead to a number of disorders, including despair and anxiety. In order to cure insomnia, this study aims to evaluate the sedative effects of PRO in Swiss mice and use an in silico approach to look into the molecular processes at play. In our investigation, five mice were given oral PRO at doses of 2.5 and 10 mg/kg. The vehicle (NC) and diazepam (DZP), which serve as a positive allosteric modulator of the gamma‐aminobutyric acid A (GABA A ) receptor and a control, respectively, were used to measure the effects utilizing parameters including sleep duration and latency. Thiopental sodium (T‐Na) was employed in this instance as a sleep aid. Molecular docking experiments were also used to quantify PRO and DZP's binding capability to the GABA A receptor, which is linked to the sedative effect. The results show that PRO significantly affects mice's sleep patterns. PRO at 2.5 and 10 mg/kg extended sleep duration and reduced sleep latency in comparison to the NC. DZP (3 mg/kg) exhibited the greatest individual effect, even though PRO (10 mg/kg) and DZP combined further enhanced both measures, indicating a synergistic action. In the in silico investigation, PRO showed a significant binding affinity to the GABA A receptor with a docking score of −9.7 kcal/mol. It created several hydrophobic contacts and 11 hydrogen bonds with significant amino acid residues. PRO induces a sedative effect in mice primarily by modulating and activating the GABAergic neurotransmission system. We recommend more clinical research to validate PRO as a trustworthy sedative agent.