The Neuroprotective Effect Of Catalpol On Alzheimer’ Disease

Objective: To observe the effect of catalpol, an iridiod glucoside,isolated from the root of Rehmannia glutinosa, on the behavior deficits andthe typical pathological hallmarks in the brain of APP/PS1doubletransgenic AD mice model, as well as to explore its possible underlyingmolecular mechanisms. Therefore, the outcome of the study may provideinsight to the prevention and treatment of AD.Methods:40APP/PS1male double transgenic mice were randomlydivided into catalpol-treated group and saline-treated group,5mg/(kg.d) ofcatalpol and the same amount of saline were injected peritoneally injectedinto the AβPP/PS1mice,10age-matched healthy mice with the samegenetic background were used as normal group. Morris water maze, openfield and EPM tests were used to check the effect of catalpol on the spatiallearning and memory, the autonomic activities and anxious emotions;Immunochemical staining was conducted to examine whether catalpolaffect the senile plaques and neurons in the brain of AD mice; Western blotwas performed to investigate the effect of catalpol on the level of BACE1protein and VEGF protein in the brains of APP/PS1double transgenic mice.Results:(1) Behavioral tests:①In the MorrisWater Maze test,catalpol-treated, saline-treated and wild-type mice had similar escapelatency(P>0.05) and path length(P>0.05) in the visible platform(P>0.05);In the hidden platform test, the e scape latency of catalpol-treated mice onday3and day4was remarkably reduced as compared with saline-treatedmice(P<0.001); In the probe trial, Catalpol-treated group and normalgroup had significantly more platform-passing times in the correctquadrant of pool than saline-treated group (P<0.01);②In the open fieldtest, the catalpol-treated group had significantly decreased time spent andcrossing length in the central area when compared to the saline-treatedgroup (P<0.01);③In the EPM test, the total arm entries were similaramong the three different groups, it showed a significant increase ofcatalpol-treated group on the open enties/total entries and duration ratioscompared with saline-treated group (P<0.01).(2) Morphological test: immunochemical staining showed that thenumber of senile plaques and apoptotic neuronal cells in the cerebral cortexand hippocampus of catalpol-treated mice were significantly decreased,while catalpol rescued the decrase of neurons and neuronal precursor cellsin the brain of AD mice.(3) Protein level test: Western blot showed that the expression ofβ-secretase BACE1, VEGF protein and PSD-95protein were significantly increased (P<0.01), compared with the saline-treated mice. However,catalpol has no effect on the APP full length protein.Conclusion: catalpol treatment can notably improved AD-associatedbehavior disorder in APP/PS1AD transgenic mice model; catalpoltreatment reduced Aβ deposition and senile plaque formation in the brain ofAPP/PS1double transgenic mice by inhibiting β-secretase cleavage of APPproteins and enhancement of vascular clearance; catalpol rescued themassive loss of neurons and synapses via promoting neurogenesis anddecreasing neuronal apoptosis.