Ferulic acid potentiates pentobarbital-induced sleep via the serotonergic system

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a widely distributed natural phenolic compound that is abundant in many plant tissues and foods. This study investigated possible mechanisms underlying the sedative-hypnotic effect of FA through behavioral pharmacology methods. FA showed dose-dependent sedative effects on locomotion activity in normal mice. FA also significantly potentiated pentobarbital-induced (45 mg/kg, i.p.) sleep by prolonging sleeping time and shortening sleep latency in a dose-dependent manner. These effects were augmented by the administration of 5-hydroxytryptophan (5-HTP), a precursor of 5-hydroxytryptamine (5-HT). With a sub-hypnotic dose of pentobarbital (25 mg/kg, i.p.), FA significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5 mg/kg, i.p.). Pretreatment with p-chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) significantly decreased the duration of pentobarbital-induced sleep, whereas FA significantly reversed this effect. These results suggest that FA has sedative-hypnotic activity, possibly mediated by the serotonergic system.