Antidepressant-like effect of essential oil of Perilla frutescens in a chronic,unpredictable,mild stress-induced depression model mice

Perilla frutescens(Perilla leaf),a garnishing vegetable in East Asian countries,as well as a plant-based medicine,has been used for centuries to treat various conditions,including depression.Several studies have demonstrated that the essential oil of P.frutescens(EOPF) attenuated the depressive-like behavior in mice.The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic,unpredictable,mild stress(CUMS)-induced mouse model.With the exposure to stressor once daily for five consecutive weeks,EOPF(3,6,and 9 mgkg-1) and a positive control drug fluoxetine(20 mgkg-1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week.Open-field test,sucrose consumption test,tail suspension test,and forced swimming test were used to evaluate the behavioral activity.The contents of 5-hydroxytryptamine(5-HT) and its metabolite,5-hydroxyindoleacetic acid(5-HIAA),in mouse hippocampus were determined by HPLC-ECD.Serum interleukin(IL)-1,IL-6,and tumor necrosis factor(TNF)- levels were evaluated by enzyme-linked immunosorbent assay(ELISA).The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus,with an increase in plasma IL-6,IL-1,and TNF- levels.CUMS also reduced open-field activity,sucrose consumption,as well as increased immobility duration in FST and TST.EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA;reduce the IL-6,IL-1,and TNF- levels.Moreover,EOPF could effectively reverse alterations in immobility duration,sucrose consumption,and open-field activity.However,the effect was not dose-dependent.In conclusion,EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression.The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.