RESUMEN
Objective To investigate the effects of ZMS,the active component of Zhimu,on amyloid precursor protein(APP) and ?-site APP cleaving enzyme 1(BACE1) in HEK293sw cells. Methods HEK293sw cells were pretreated with different concentrations of ZMS in routine culture medium for 24 h,and then serum-free medium with ZMS was used for further culture for 48 h.Cells were examined for expression of APP and ?-secretase BACE1 with Western blotting and RT-PCR,and were then examined for BACE1 activity with fluorescence method. Results 1 ?mol/L and 10 ?mol/L ZMS significantly decreased the expression of BACE1 mRNA and protein,while had no effect on the expression of APP mRNA and protein.It was indicated by fluorescence analysis that 10 ?mol/L ZMS significantly decreased the ?-secretase activity.Conclusion ZMS significantly decreases the activity and expression of ?-secretase BACE1,while has no effect on the expression of APP in HEK293sw cells.
RESUMEN
Aim To observe the effect of ZDY102, a C25 stereo-isomer of ZMS, the active component of Zhimu, on brain M receptor density of dementia model animals and the correlation with its effect on learning/memory ability. Methods The rats were randomly divided into five groups: control group, model group, model given orally for 2 months with 3.6 mg?kg -1?d -1 of ZDY102 treatment, model treated with 9.0 mg?kg -1?d -1 of ZDY102, and model treated with 18.0 mg?kg -1?d -1 of ZDY102. Dementia model was produced by single unilateral injection of 4 ?l of normal saline containing 4 ?g of ?-amyloid (25～35) and 1 ?g of ibotenic acid into right basal ganglion region with the aid of a stereotaxic equipment. The brain muscarinic receptor density was analyzed with single-site binding assay using 3H-quinuclidinyl benzilae(QNB). The learning/memory ability was measured by Y-maze performance. Results Two months after model production, the learning and memory ability as well as the density of muscarinic receptor in brain were significantly decreased in model rats compared with those in control rats. Parallel models treated with daily oral administration of ZDY102 for two months improved in learning and memory ability and their muscarinic receptor density was significantly increased when compared with model rats. The correlation coefficient between total M receptor densities and the learning/memory ability was significant when examined with linear regression. Conclusion ZDY102 can significantly improve the learning and memory ability and increase the brain muscarinic receptor density of the model. Since brain muscarinic receptors are closely correlated to learning and memory, up-regulation of M receptor density might play a very important role in the therapeutic effect of ZDY102.
RESUMEN
AIM To study the effect of ZMS, an active component of traditional Chinese herb Zhimu, on two neurotrophins in brains of aged rats. METHODS The function of learning and memory was detected by Y-maze. BDNF and NGF in brain were determined by ELISA. Rats were divided into three groups, young, aged, and aged treated with ZMS for two months at a dose of 18mg/kg/d which is equivalent to the dose recommended for clinical use. RESULTS The learning and memory ability are impaired in aged animals and ZMS is effective in improving the learning and memory ability of such animals. BDNF content of whole brain is lowered in aged rats when compared with young rats. ZMS is able to raise the BDNF content to a higher level. The NGF contents of young, aged and aged treated with ZMS groups were not significantly different from each other. CONCLUSIONS ZMS is able to raise brain BDNF in aged rats and thus to protect cholinergic neurons from degeneration. It is very probable that this action is one of the mechanisms of ZMS in improving the ability of learning and memory.