Anxiolytic and antidepressant like effects of natural food flavour (E)-methyl isoeugenol

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Abstract
(E)-methyl isoeugenol (MIE) is a natural food flavour that constitutes 93.7% of an essential oil from Pimenta pseudocaryophyllus leaf. The leaf extracts of this species are used as a calming agent. As a ubiquitous food additive, the application of MIE for treating mood disorders appears to be globally attractive. Hence, we sought to evaluate general pharmacological activities, anticonvulsant, anxiolytic and antidepressant effects and the possible mechanisms of MIE actions. Administration of MIE was carried out prior to the exposure of a male Swiss mice to general behavioural tests, barbiturate sleep, PTZ-induced convulsion, light dark box (LDB), elevated plus maze (EPM), wire hanging, open field (OF) and forced swimming test (FST). The involvement of monoamine system was studied by mice pretreatment with WAY100635 (antagonist of 5-HT1A), α-methyl-p-tyrosine (AMPT; depletor of catecholamine) or p-chlorophenylalanine (PCPA; depletor of serotonin storage). There was no record of neurotoxic effect or animal's death during the course of general pharmacological tests. MIE at 250 and 500 mg kg−1 potentiated the hypnotic effect of sodium pentobarbital. However, MIE did not protect against PTZ-induced convulsion. Except for MIE at 500 mg kg−1, parameters evaluated in the LDB, EPM and OF demonstrated an anxiolytic like property of MIE. This effect was blocked by WAY100635 pretreatment. MIE at 500 mg kg−1 elicited a reduction in locomotor activity of the mice in the OF. Anti-immobility effect of MIE 250 mg kg−1 in the FST suggested an antidepressive like property. Unlike AMPT, pretreatment with PCPA reversed the antidepressant like effect of MIE. Our findings demonstrated anxiolytic and antidepressant like properties of (E)-methyl isoeugenol and suggested the participation of serotonergic pathways.

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