Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats / 中国实验方剂学杂志

ABSTRACT

Objective::To investigate the effect and possible mechanism of Liuwei Dihuangtang on memory impairment in rats with chronic depression. Method::Female Wistar rats were randomly divided into normal group (normal saline), chronic unpredictable mild stress (CUMS) model group (normal saline), and low, medium and high-dose Liuwei Dihuangtang groups (2.60, 7.81, 23.50 g·kg-1·d-1). Except for the normal group, all of the other groups were included in the chronic unpredictable mild stress model. Weight were measured every week, changes in their behavioral indicators were observed. The mRNA expressions of G protein-coupled estrogen receptor (GPR30), phosphatidylinositol 3-kinase(PI3K), cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the rat hippocampus were determined by real-time fluorescence quantification polymerase chain reaction (Real-time PCR). The concentration of serum estrogen was detected by enzyme-linked immunosorbent assay (ELISA) method. Result::Compared with normal group, model group showed decreases in weight, activity and interest. Liuwei Dihuangtang (2.60, 7.81, 23.50 g·kg-1) significantly increased the sucrose preference of CUMS rats (P<0.01) and standing times in the open field test (P<0.01), doses of 7.81, 23.50 g·kg-1 significantly increased the total distance of the open field test (P<0.05, P<0.01), doses of 2.60, 7.81 g·kg-1 shortened the latency of water maze experiment (P<0.01), and dose of 7.81 g·kg-1 increased serum estrogen concentration (P<0.05). The mRNA expressions of GPR30, PI3K, CREB and BDNF in hippocampus of CUMS model group decreased significantly (P<0.05, P<0.01), but the mRNA expression levels of GPR30, CREB in hippocampus of 2.60 g·kg-1 dose Liuwei Dihuangtang group increased significantly (P<0.05, P<0.01), and the mRNA expression levels of GPR30, PI3K, CREB, BDNF in hippocampus of 7.81 g·kg-1 dose group increased significantly as well (P<0.05, P<0.01). Conclusion::Liuwei Dihuangtang has effect in resisting depression, and reversing depression-like behavior and learning and memory impairment in CUMS rats, with the best effect in the medium-dose Liuwei Dihuangtang group. Its mechanism may be related to increase of serum estrogen and mRNA expressions of GPR30, PI3K, CREB and BDNF in rat hippocampus.