Sedative-hypnotic like effect of 5-methoxyflavone in mice and investigation on possible mechanisms by in vivo and in silico methods

Flavonoids have been shown to possess central nervous system (CNS) depressant effect mediated through the ionotropic GABA_A receptors. In the present study, 5-methoxyflavone was evaluated for sedative-hypnotic like activity in mice and the mechanisms involved by employing a battery of tests including molecular docking studies. In the open field test, 5-methoxyflavone in various doses (50, 100 and 150 mg/kg, i.p) exhibited a significant and dose-dependent reduction in the spontaneous locomotor activity (F (530) = 87.17 P < 0.001). Pretreatment with 5-methoxyflavone decreased the latency to sleep induction after pentobarbitone or ether administration and also significantly increased the duration of sleep (p < 0.001). A significant and dose-dependent myorelaxant effect was observed with 5-methoxyflavone in the inclined plane, horizontal wire test and rota rod test. Pretreatment with picrotoxin, bicuculline, glycine, caffeine or NMDA either decreased or completely abolished the hypnotic effect of 5-methoxyflavone in mice. The above results revealed the involvement of GABA_A, adenosine, glycine and NMDA receptors in the hypnotic effect of 5-methoxyflavone. The results of in silico studies indicated that, 5-methoxyflavone exhibits good binding affinity towards these receptors by H-bond interactions. In conclusion, the present study identified a novel and potential sedative-hypnotic like effect of 5-methoxyflavone involving multiple mechanisms.