Objective: To study the mechanism of total saponins of Baihe Zhimu Tang (SBZ) in regulating 5-hydroxytryptamine(5-HT) function for treatment of major depression

and to explore the pharmacodynamic advantages of SBZ versus total saponins of Lilii Bulbus (SL) or total saponins of Anemarrhenae Rhizoma (SA). Method: The depression model rats were induced by using unpredictable mild stimulation combined with feeding alone

and were divided equally into five groups:the major depression model group (MDD)

total saponins of SL group (100 mg·kg-1)

total saponins of SA group (220 mg·kg-1)

total saponins of SBZ group (240 mg·kg-1) and fluoxetine hydrochloride group (FLU

10 mg·kg-1). Another normal group was also set up

n=11 in each group. The normal group and MDD group received the equal amount of 0.5% Arabic gum solution

and corresponding doses of drugs were given in other groups. The immobility time in forced swimming test and the levels of 5-HT in blood and cerebral tissues of experiment rats were measured. Immunofluorescence staining was used to detect the positive expressions of 5-HT1a in the cerebral cortex and hippocampus. Reverse transcription and polymerase chain reaction (Real-time PCR) was used to test the mRNA transcription levels of genes in hippocampus:5-HT synthesis gene tryptophan hydroxylase(1TPH1)

Synaptic vesicular monoamine transporter18A1(SLC18A1)

synaptic protein-25(SNAP25); the expression of RGS19 in blood and hypothalamus were also detected. The expression of 5-HT transporter protein (SERT) in hippocampus and hypothalamus was detected by Western blot. Result: There was a significant difference between model group and normal group (P<0.01). As compared with model group

SBZ significantly reduced the immobility time of depressed rats in forced swimming test(P<0.05)

up-regulated 5-HT levels in blood and brain (P<0.05) and the positive expression of 5-HT1a in cerebral cortex and hippocampus(P<0.05

P<0.01). According to the results of SBZ significantly increased the mRNA expression of TPH1

SLC18A1 and SNAP25 in hippocampal

and up-regulated the mRNA expressions of RGS19 in blood and hypothalamus(P<0.05

P<0.01); SBZ reduced the expression of SERT protein in hippocampus and hypothalamus(P<0.01)

thereby increased the central content of 5-HT. Conclusion: SBZ can activate 5-HT synthesis gene TPH1 expression

down-regulate SERT expression

inhibit reuptake

increase the content of 5-HT in central tissues. SBZ could also up-regulate the expression of 5-HT1a receptor and its downstream gene RGS19 to regulate receptor function and signal transduction; improve the neurotransmitters transmission ability by up-regulating the expression of SLC18A1 and SNAP25

and finally achieve the anti-depression function. Results showed that SBZ had significant pharmacodynamic advantages in antidepressant efficacy as compared to SL and SA.