Shen-Zhi-Ling oral solution improves learning and memory ability in Alzheimer’s disease mouse model

OBJECTIVE: To investigate the effector mechanisms and effector targets of Shen-Zhi-Ling (SZL) oral solution in the treatment of Alzheimer's disease (AD). METHODS: In this study, we carried out gavage with SZL oral solution in an APP/PS-1 heterozygous double transgenic AD mouse model for 12 continuous weeks. Haematoxylin and eosin staining, Nissl staining and Annexin V/Propidium Iodide staining were used to detect the brain histopathology in AD mouse model. Immunofluorescence staining was used to detect the expression levels of autophagy's proteins. Morris water maze test was used to detect the learning and memory ability in AD mouse model. RESULTS: Pathological results showed that neuronal loss in the hippocampus of mice in the SZL intervention group was significantly alleviated and the number of apoptotic neurons was significantly decreased compared with the control group (physiological saline and non-intervention groups). Immunofluorescence staining results showed that the expression of autophagy activators, Beclin-1 and LC3B, was significantly increased in the hippocampal neurons of mice of the SZL intervention group, while the expression of the apoptotic factor, caspase- 3, was significantly decreased. At the same time, hippocampal accumulation of Aβ42 protein was significantly decreased. In addition, results of the water maze experiment showed that the latency period in mice from the SZL intervention group was significantly reduced. CONCLUSION: In summary, we believe that the SZL oral solution significantly activates autophagy in hippocampal neurons, effectively reducing the accumulation of Aβ42 peptides, alleviating neuronal injury and apoptosis, and ultimately improving the cognitive function in a mouse model of AD.