Evaluation of the Sedative Activity of Naringenin: In Vivo Study with Pharmacokinetics and Molecular Docking Insights

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Publicado en:ChemistryOpen vol. 14, no. 10 (Oct 1, 2025)
Autor principal: Bishwas, Dipu
Otros Autores: Bhuia, Md. Shimul, Sheikh, Salehin, Alfaifi, Mohammed, Malik, Abdul, Siddiqui, Nikhat J., Jain, Divya, Bappi, Mehedi Hasan, Islam, Muhammad Torequl
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John Wiley & Sons, Inc.
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024 7 |a 10.1002/open.202500114  |2 doi 
035 |a 3260492070 
045 0 |b d20251001 
084 |a 233130  |2 nlm 
100 1 |a Bishwas, Dipu  |u Department of Pharmacy, Pabna University of Science and Technology, Pabna, Bangladesh 
245 1 |a Evaluation of the Sedative Activity of Naringenin: In Vivo Study with Pharmacokinetics and Molecular Docking Insights 
260 |b John Wiley & Sons, Inc.  |c Oct 1, 2025 
513 |a Journal Article 
520 3 |a This research is designed to investigate the sedative effects of naringenin (NAR) and diazepam against thiopental sodium‐induced sleeping mice. NAR (5 and 10 mg kg), diazepam (DZP) (2 mg kg), flumazenil (FLN) (0.1 mg kg), and their combinations are administered intraperitoneally to mice. After 30 min, sleep is induced with intraperitoneal thiopental sodium (20 mg kg), and sleep latency and duration are measured. In silico analysis investigates the role of GABA receptors. NAR significantly reduces sleep latency and prolongs sleep duration in a dose‐dependent manner, with the combination of NAR‐10 and DZP‐2 showing a synergistic effect. The combination of the antagonist (FLN) (NAR‐10 and FLN‐0.1) indicates that latency increases and sleep duration decreases compared to NAR‐10 alone. Furthermore, in silico docking studies corroborates these results, demonstrating a significant binding affinity of NAR (−8.3 kcal mol), which is comparable to the standard ligand DZP (−8.7 kcal mol) and FLN (−7.0 kcal mol) for the GABAA (6X3X) receptor, indicating a GABAergic mechanism. Pharmacokinetics and toxicity evaluations confirm NAR's potential as a safe therapeutic agent, with a high LD50 (2000 mg kg) and minimal toxicity. These findings highlight NAR's potential as a GABAergic sedative agent, requiring further research before being used clinically to treat sleep disorders. 
653 |a Insomnia 
653 |a Receptors 
653 |a Benzodiazepines 
653 |a Neurotoxicity 
653 |a Sleep 
653 |a Toxicity 
653 |a Molecular docking 
653 |a Cytotoxicity 
653 |a Brain research 
653 |a Permeability 
653 |a Pharmacology 
653 |a Pharmacokinetics 
653 |a Synergistic effect 
653 |a Ligands 
653 |a Cardiotoxicity 
653 |a Nervous system 
653 |a Biocompatibility 
653 |a In vivo methods and tests 
653 |a Natural products 
653 |a Sodium 
653 |a Drug dosages 
700 1 |a Bhuia, Md. Shimul  |u Bioinformatics and Drug Innovation Laboratory, Bioluster Research Center Ltd., Gopalganj, Dhaka, Bangladesh 
700 1 |a Sheikh, Salehin  |u Bioinformatics and Drug Innovation Laboratory, Bioluster Research Center Ltd., Gopalganj, Dhaka, Bangladesh 
700 1 |a Alfaifi, Mohammed  |u Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia 
700 1 |a Malik, Abdul  |u Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia 
700 1 |a Siddiqui, Nikhat J.  |u Department of Internal Surgical Nursing, College of Nursing, King Saud University, Riyadh, Saudi Arabia 
700 1 |a Jain, Divya  |u Department of Microbiology, School of Applied & Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India 
700 1 |a Bappi, Mehedi Hasan  |u School of Pharmacy, Jeonbuk National University, Jeonju, Republic of Korea 
700 1 |a Islam, Muhammad Torequl  |u Bioinformatics and Drug Innovation Laboratory, Bioluster Research Center Ltd., Gopalganj, Dhaka, Bangladesh 
773 0 |t ChemistryOpen  |g vol. 14, no. 10 (Oct 1, 2025) 
786 0 |d ProQuest  |t Materials Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3260492070/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text  |u https://www.proquest.com/docview/3260492070/fulltext/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3260492070/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch