The citrus peel flavonoid tangeretin(TAN)has diverse biological activities,including antioxidant,antiinflammatory,anti-tumor,hepatoprotective,and neuroprotective effects.This study emphasizes evaluating the anxiolytic...The citrus peel flavonoid tangeretin(TAN)has diverse biological activities,including antioxidant,antiinflammatory,anti-tumor,hepatoprotective,and neuroprotective effects.This study emphasizes evaluating the anxiolytic effect of TAN on mice.Additionally,we conducted in silico investigations to examine the potential molecular mechanisms behind the anxiolytic effect of TAN.For this,adult male Swiss albino mice were treated with TAN(10 and 20 mg/kg,p.o.)with or without the standard GABAergic agonist drug diazepam(DZP:2 mg/kg,p.o.)and/or antagonist drug flumazenil(FLU:0.1 mg/kg,i.p.)and checked for different locomotor behaviors using various mouse models.The molecular docking study of TAN was conducted against GABAA receptor subunits.Findings suggest that TAN dose-dependently and significantly(p<0.05)increased locomotor activities such as the number of field crosses,hole crosses,swings,and light residence time while decreasing the grooming and rearing parameters of the animals.With DZP,it significantly(p<0.05)reduced the test parameters while altering these parameters with FLU.In molecular docking,TAN has a strong binding affinity of-6.6 and-7.0 kcal/mol for the α2 and α3 subunits of the GABAA receptor,respectively,whereas the standard drugs DZP and FLU showed binding affinities between-6.0 and-6.7 kcal/mol for these subunits.MD simulations showed that TAN interacts with α3 subunits in a way similar to DZP,with similar RMSD and RMSF values and ligand properties.TAN also demonstrated acceptable drug-likeness and pharmacokinetics.Taken together,TAN augmented the anxiolytic effect of DZP while reducing the effect of FLU in mice.展开更多
基金the research supporting project number RSPD2024R744,King Saud University,Riyadh,Saudi Arabia.
文摘The citrus peel flavonoid tangeretin(TAN)has diverse biological activities,including antioxidant,antiinflammatory,anti-tumor,hepatoprotective,and neuroprotective effects.This study emphasizes evaluating the anxiolytic effect of TAN on mice.Additionally,we conducted in silico investigations to examine the potential molecular mechanisms behind the anxiolytic effect of TAN.For this,adult male Swiss albino mice were treated with TAN(10 and 20 mg/kg,p.o.)with or without the standard GABAergic agonist drug diazepam(DZP:2 mg/kg,p.o.)and/or antagonist drug flumazenil(FLU:0.1 mg/kg,i.p.)and checked for different locomotor behaviors using various mouse models.The molecular docking study of TAN was conducted against GABAA receptor subunits.Findings suggest that TAN dose-dependently and significantly(p<0.05)increased locomotor activities such as the number of field crosses,hole crosses,swings,and light residence time while decreasing the grooming and rearing parameters of the animals.With DZP,it significantly(p<0.05)reduced the test parameters while altering these parameters with FLU.In molecular docking,TAN has a strong binding affinity of-6.6 and-7.0 kcal/mol for the α2 and α3 subunits of the GABAA receptor,respectively,whereas the standard drugs DZP and FLU showed binding affinities between-6.0 and-6.7 kcal/mol for these subunits.MD simulations showed that TAN interacts with α3 subunits in a way similar to DZP,with similar RMSD and RMSF values and ligand properties.TAN also demonstrated acceptable drug-likeness and pharmacokinetics.Taken together,TAN augmented the anxiolytic effect of DZP while reducing the effect of FLU in mice.
