Md Sakib Al Hasan, Md Shimul Bhuia, Salehin Sheikh, Sumaya Akter Bithi, Md Abu Saim, Hossam Kamli, Siddique Akber Ansari, Nowreen Tabassum Ahammed, Muhammad Torequl Islam
{"title":"Assessment of sedative activity of Chrysin: Behavioral approach with pharmacokinetics, toxicological profile and molecular docking.","authors":"Md Sakib Al Hasan, Md Shimul Bhuia, Salehin Sheikh, Sumaya Akter Bithi, Md Abu Saim, Hossam Kamli, Siddique Akber Ansari, Nowreen Tabassum Ahammed, Muhammad Torequl Islam","doi":"10.1016/j.sleep.2024.12.007","DOIUrl":null,"url":null,"abstract":"<p><p>The purpose of this study was to investigate the sedative effects of Chrysin (CHR) along with modulatory effects on diazepam (DZP) and flumazenil (FLU) in an animal sleep model produced by thiopental sodium (TS). Additionally, we explored the pharmacokinetics and potential GABA<sub>A</sub> receptor interactions of CHR through computational studies. Swiss albino mice were treated with intraperitoneal administration of CHR (5 and 10 mg/kg), DZP (2 mg/kg), and FLU (0.1 mg/kg) either alone or in combination. Sleeping onset and duration were measured following TS administration. Molecular docking was performed to investigate CHR's binding affinity with GABA<sub>A</sub> (PDB: 6X3X) receptors. Results found that CHR significantly (p < 0.05) reduced sleep latency and increased sleep duration in a dose-dependent manner compared to the control group. The highest dose (CHR-10) exhibited the most potent significant sedative effect with onset (11.57 ± 1.74 min) and duration (172.86 ± 7.37 min). Combination therapy of CHR-10 with DZP resulted in synergistic effects, further enhancing sleep duration. In molecular docking, CHR demonstrated a higher binding affinity (-8.9 kcal/mol) for GABA<sub>A</sub> receptors compared to DZP (-8.7 kcal/mol) and FLU (-6.6 kcal/mol). CHR also showed favorable pharmacokinetic properties with high intestinal absorption and low toxicity. CHR exhibits promising sedative activity, with the potential to enhance the effects of traditional sedatives like DZP. However, further research, including clinical trials and detailed mechanistic studies, is warranted to explore its full therapeutic potential.</p>","PeriodicalId":21874,"journal":{"name":"Sleep medicine","volume":"126 ","pages":"88-96"},"PeriodicalIF":3.8000,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sleep medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.sleep.2024.12.007","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The purpose of this study was to investigate the sedative effects of Chrysin (CHR) along with modulatory effects on diazepam (DZP) and flumazenil (FLU) in an animal sleep model produced by thiopental sodium (TS). Additionally, we explored the pharmacokinetics and potential GABAA receptor interactions of CHR through computational studies. Swiss albino mice were treated with intraperitoneal administration of CHR (5 and 10 mg/kg), DZP (2 mg/kg), and FLU (0.1 mg/kg) either alone or in combination. Sleeping onset and duration were measured following TS administration. Molecular docking was performed to investigate CHR's binding affinity with GABAA (PDB: 6X3X) receptors. Results found that CHR significantly (p < 0.05) reduced sleep latency and increased sleep duration in a dose-dependent manner compared to the control group. The highest dose (CHR-10) exhibited the most potent significant sedative effect with onset (11.57 ± 1.74 min) and duration (172.86 ± 7.37 min). Combination therapy of CHR-10 with DZP resulted in synergistic effects, further enhancing sleep duration. In molecular docking, CHR demonstrated a higher binding affinity (-8.9 kcal/mol) for GABAA receptors compared to DZP (-8.7 kcal/mol) and FLU (-6.6 kcal/mol). CHR also showed favorable pharmacokinetic properties with high intestinal absorption and low toxicity. CHR exhibits promising sedative activity, with the potential to enhance the effects of traditional sedatives like DZP. However, further research, including clinical trials and detailed mechanistic studies, is warranted to explore its full therapeutic potential.
期刊介绍:
Sleep Medicine aims to be a journal no one involved in clinical sleep medicine can do without.
A journal primarily focussing on the human aspects of sleep, integrating the various disciplines that are involved in sleep medicine: neurology, clinical neurophysiology, internal medicine (particularly pulmonology and cardiology), psychology, psychiatry, sleep technology, pediatrics, neurosurgery, otorhinolaryngology, and dentistry.
The journal publishes the following types of articles: Reviews (also intended as a way to bridge the gap between basic sleep research and clinical relevance); Original Research Articles; Full-length articles; Brief communications; Controversies; Case reports; Letters to the Editor; Journal search and commentaries; Book reviews; Meeting announcements; Listing of relevant organisations plus web sites.