Protective effects of Cerebralcare Granule® against the learning and memory impairment in a mouse model of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by the impairment of cognition, memory, language and behavioral function. So far, there are no efficacious drugs approved for the treatment of AD. Cerebralcare Granule (CG) is a compound Chinese medicine used for treatment of headache and dizziness associated with cerebrovascular diseases. Increasing evidence indicates that CG can improve the cerebral microcirculatory disturbance and has a protective effect on the neural damage, which suggests CG may be a promising medicine for AD.Herein, this study investigated the potential effect of CG on AD in the Senescence Accelerated Prone Mouse 8 (SAMP8) mouse. Male 7‐month‐old SAMP8 mice were randomly divided into five groups: AD model group, CG treatment groups (935, 1870 and 3740 mg/kg), and donepezil treatment group (1.3 mg/kg). After intragastric administration with CG for two months, behavioral tests were conducted to evaluate the neuroprotective effects of CG. Ultrastructural changes of neurons and synapses in the hippocampus of the mice were observed. The expressional levels of BDNF, NGF, and TrkA were analyzed through immunohistochemistry. Western blotting was used to analyze the expressional levels of GAP‐43, SYP, and PSD‐95. Biochemical analysis was performed to assess the activities of total antioxidant capacity (T‐AOC), SOD, and GSH‐Px, and the content of GSH and MDA.The findings showed that CG dose‐dependently attenuated the impairment of spontaneous alternation behavior and donepezil treatment had a significant effect in attenuating the impairment of spontaneous alternation behavior. The mice in the CG‐treatment groups (1870 and 3740 mg/kg) consistently took a less time to find the platform than the model group in the Morris water maze test. CG and donepezil treatment alleviated the synaptic ultrastructure damage in the hippocampal CA1 region of the SAMP8 mouse and normal synaptic morphology and structure was maintained. CG can increase the levels of activities of GSH (change ratio of 45.5%), T‐AOC (change ratio of 40.9%), SOD (change ratio of 171.9%) and GSH‐Px (change ratio of 117.4%), and decrease the content of MDA (change ratio of 60.7%). Compared with the model group, the group with 3740mg/kg CG showed a significantly increased expression of SYP and PSD‐95 in the hippocampus and cerebral cortex. The group treated with either 3740 mg/kg CG or with donepezil showed a significantly increased expression of BDNF(change ratio of 38.2%), NGF (change ratio of 41.9%) and the neurotrophic factor receptor TrkA (change ratio of 46.9%), compared with the model group.The above results suggest that CG can alleviate the learning and memory impairment of AD mice via inhibiting oxidative stress, increasing neurotrophic factors and mitigating synaptic damage.Support or Funding InformationSupported by Tianjin Science and Technology's Plan (16PTSYJC00270).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.