Tangeretin enhances sedative activity of diazepam in Swiss mice through GABAA receptor interaction: In vivo and in silico approaches.

作者：Md. Sakib Al Hasan, Md. Shimul Bhuia, R. Chowdhury, Zakir Husain, Md. Saifiuzzaman, Emon Mia, M. Akbor, Noshin Tasnim Yana, M. Islam, S. Ansari, Irfan Aamer Ansari, Md. Torequl Islam · 发表于：Neuroscience · 年份：2025 · DOI：10.1016/j.neuroscience.2025.03.004 · 被引用次数：18 · 研究领域：Medicine

The citrus peel flavonoid tangeretin (TAN) has diverse biological activities, including antioxidant, anti-inflammatory, antitumor, hepatoprotective, and neuroprotective effects. This study investigates the sedative effects of TAN, in Swiss albino mice using in vivo and in silico approaches. TAN (10 and 20 mg/kg, i.p.) was administered alone and in combination with diazepam (DZP, 2 mg/kg, i.p.) and flumazenil (FLU, 0.1 mg/kg, i.p.) to evaluate its impact on thiopental sodium (TS)-induced sleep, locomotor activity, and dark-light behavior. Results demonstrated that TAN at 10 mg/kg significantly (p < 0.05) reduced sleep onset latency and increased sleep duration, with a synergistic effect observed when combined with DZP. In locomotor activity tests, TAN dose-dependently decreased the distance traveled, while the combination with DZP further enhanced this effect. Dark-light tests revealed that TAN increased dark residence time, indicating potential anxiolytic properties. Molecular docking studies showed that TAN binds to the GABAA receptor (α1 and β2 subunits) with a binding affinity of -6.6 kcal/mol, suggesting its interaction with GABAergic pathways. Pharmacokinetic analysis indicated high intestinal absorption and compliance with Lipinski's rule of five, with a favorable safety profile (LD50 = 5000 mg/kg). Overall, TAN enhances the sedative effects of DZP through GABAA receptor modulation, highlighting its potential as a natural sedative agent. Further research should explore ...