ObjectiveTo investigate the antidepressant-like effects of combination of ginseng total saponins(GTS)and polygala tenuifolia total glycosiders (PTG) in mice. MethodThe factorial design analysis of variance (ANOVA) was employed to investigate the appropriate combination of GTS and PTG. The forced swim and tail suspension test were performed to evaluate the efficacy of SYG. Open field test was used to assess the psycho-stimulant side-effects. C57BL/6J mice (for tail suspension test) and ICR mice (for forced swim test) were randomly separated into 11 groups (n = 10):control (distilled water), positive control (10 mg/kg, paroxetine for TST, amitriptyline for FST), or treated with SYG (nine groups). All drugs and water were administered by gastric gavages (20 mL/kg) once daily for seven days. The behavioural tests in mice were conducted on the 7th day after the last administration. To compare the antidepressant effects of SYG, GTS and PTG, C57BL/6J mice (for tail suspension test) and ICR mice (for forced swim test) were randomly separated into 13 groups (n = 10):control (distilled water), positive control (10 mg/kg, paroxetine for TST, amitriptyline for FST), or treated with SYG (37.5,5, 150 mg/kg), GTS, PTG (18.5,7.5,5, 150 mg/kg). All drugs and water were administered by gastric gavages (20 mL/kg) once daily for seven days. The behavioural tests in mice were conducted on the 7th day after the last administration. ResultsIn the factorial design, SYG reduced the immobility time in the tail susupension and forced swim test at doses of 75 mg/kg (GTS∶PTG = 50∶25) and 150 mg/kg (GTS∶PTG = 100∶50) (P < 0.05). Accordingly, the appropriate combination of GTS and PTG was 2∶1. SYG did not produce significant effects on the locomotor activity in the open-field test. In the subsequent test, GTS reduced the immobility time in the tail suspension test at doses of 5,0 mg/kg(P < 0.01,P < 0.05), but did not reduce the immobility time in the forced swim test. PTG reduced the immobility time in the forced swim test at doses of 18.5,7.5 mg/kg(P < 0.01,P < 0.05), but did not reduce the immobility time in the tai suspension test. However, SYG reduced the immobility time both in the forced swim and tail suspension test at doses of 37.5～150 mg/kg(P < 0.01,P < 0.05). ConclusionThe prescription composed of GTS and PTG could be used as a potential effective antidepressant candidate drug after further research has been done. 