Ferulic acid possesses anxiolytic activity: evidence for the involvement of serotonergic and noradrenergic systems

The current study aims to evaluate any potential anxiolytic effects and the action mechanisms of ferulic acid, a phenolic phytochemical compound, in mice. The anxiolytic activity of ferulic acid at the doses of 0.1, 1, 10, and 100 mg/kg, p.o in female BALB/c mice was assessed by open field, hole-board and elevated plus maze tests. The possible roles of noradrenergic, serotonergic, and GABAergic modulation in the anxiolytic action of 100 mg/kg ferulic acid were also investigated by pretreatment with 5 mg/kg (i.p.) yohimbine, 1 mg/kg (i.p.) WAY-100635, and 3 mg/kg (i.p.) flumazenil, respectively, in the hole-board and open field tests. Similar to the positive standard diazepam (1 mg/kg, i.p); without altering the locomotor activity, 100 mg/kg ferulic acid significantly altered all the parameters related to anxiolytic activity, whereas 0.1 and 10 mg/kg doses were found to be effective in only some parameters in elevated plus-maze and open field tests, suggesting a U-shaped dose-response pattern. The anxiolytic effect of 100 mg/kg ferulic acid was significantly antagonized by the pretreatment with 5-HT_1A receptor antagonist WAY-100635 and especially by α-2 adrenoceptor antagonist yohimbine while the anxiolytic action was not blocked by GABA_A/BZ receptor antagonist flumazenil pretreatment. The findings imply that ferulic acid's anxiolytic effect is mediated by the activation of α-2 adrenoceptors and 5-HT_1A receptors. In conclusion, it is possible to say that ferulic acid can be a safe potential agent which that be used alone or in combination with current effective treatments for anxiety.