Objective: To investigate the onset time and duration of action for the antidepressant effect of total saponins from Bupleuri Radix

and observe their effects on corticosterone damage-induced depression behavior and learning and memory impairment in mice. Method: Male ICR mice were randomly divided into normal group (distilled water)

total saponins from Bupleuri Radix low

middle and high dose groups (12.5

25

50 mg·kg-1).They were weighed every week

and field experiment was conducted after drug administration for 13 days.Total saikosaponins was given intragastrically once a day for 14 consecutive days. The effects of total saponins from Bupleuri Radix on motionless time in forced-swimming test were observed after the last administration at different time (1 h

3 d

6 d). Male c57BL/6J mice were randomly divided into normal group

corticosterone (CORT) group

citalopram group (10 mg·kg-1) and total saponins from Bupleuri Radix group (25 mg·kg-1).Corticosterone (35 mg·L-1

equivalent to 5 mg·kg-1·d-1) was delivered for 5 weeks in drinking water in CORT group

citalopram group and total saponins from Bupleuri Radix group.3 weeks after modeling

total saponins from Bupleuri Radix were given by ig administration for 2 weeks until week 5; citalopram was also given by ig administration for 2 weeks. 1 day after drug administration

forced swimming test and water maze test were conducted. After the behavioral experiment

3 mice were taken from each group. They were sacrificed then

and hippocampus was taken to detect the expression levels of brain derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB)by Western blot. Result: As compared with the normal group

total saponins from Bupleuri Radix had no effects on weight and moving distance and velocity in field experiment after 14 days administration

but could decrease the motionless time in forced swimming test at different time (1 h and 3 d after drug with drawal) (P<0.05

P<0.01). 6 days after drug withdrawal

total saponins from Bupleuri Radix 25 and 50 mg·kg-1 could still shorten the motionless time in forced swimming test (P<0.05). Two weeks treatment with total saponins from Bupleuri Radix at dose of 25 mg·kg decreased the motionless time in forced swimming test (P<0.01) and shorten the latency to reach the platform

and increase the number of platform crossing times in Morris Water Maze (P<0.05); in addition

they could increase the BDNF and Trk B levels in the hippocampus of mice with corticosterone damage (P<0.01). Conclusion: Total saponins from Bupleuri Radix could have a rapid and sustained antidepressant activity and reverse the depression-like behavior as well as learning and memory impairment induced by corticosterone damage. The mechanism may be associated withup-regulating BDNF and Trk B expression levels in the hippocampus of mice.