Shenghui Granules Improve Learning Memory in Alzheimer's Disease Mice by Inhibiting PI3K/Akt/mTOR Signaling Pathway
Objective To investigate the effect of Shenghui Granules on the learning memory ability of Alzheimer's disease(AD)mice based on the Phosphatidylinositol 3-kinase(PI3K)/Protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Thirty six-month-old male APP/PS1 double transgenic mice were randomly divided into the model group,the Shenghui Granules group(7.02 g/kg)and the Donepezil group(0.65 mg/kg),with 10 mice in each group,and 10 C57BL/6J mice were selected as the control group.the drugs were administered once daily for 4 weeks,and both of the control and model groups were given equal volume of saline.Morris water maze was used to test the learning memory ability,HE staining was used to observe the pathological morphological changes in hippocampal CA1 area,Immunohistochemistry was used to detect the expression level of Aβ1-42 and P-Tau416 in hippocampal CA1 area,and Western Blot was used to detect the expression level of PI3K/Akt/mTOR pathway proteins and their phosphorylated proteins and Beclin 1,p62 and LC3 proteins in hippocampal area.Results Compared with the control group,mice in the model group showed an increase in platform latency and total swimming distance(P＜0.01)and a decrease in the number of platform crossings and dwell time in the target quadrant(P＜0.01);a decrease in the number of cells in the hippocampal CA1 region,a sparse arrangement and a decrease in cellular hierarchy;an increase in the expression of A β1-42 and P-Tau416 proteins(P＜0.01);an increase in PI3K,p-PI3K,Akt,p-Akt,mTOR,p-mTOR and p62 protein expression levels(P＜0.01);and a decrease in Beclin 1 protein expression levels and LC3 Ⅱ/LC3 Ⅰ ratio(P＜0.01).Compared with the model group,the platform latency and total swimming distance of mice in the Shenghui Granules group and Donepezil group were reduced(P＜0.01,P＜0.05),and the number of platform crossings and dwell time in the target quadrant were increased(P＜0.01,P＜0.05);the number of cells in the CA1 area of the hippocampus was increased,with relatively intact structure;the levels of p-Tau416,PI3K,p-PI3K,Akt,p-Akt,mTOR,p-mTOR and p62 protein expression were all decreased(P＜0.01,P＜0.05),and the levels of Beclin 1 protein expression were all upregulated(P＜0.01);Aβ1-42 protein expression level was decreased and LC3 Ⅱ/LC3 Ⅰ ratio was up-regulated in the Shenghui Granules group(P＜0.01).Conclusion Shenghui Granules inhibits the PI3K/Akt/mTOR signaling pathway,induces cellular autophagy,promotes the clearance of A β,phosphorylated Tau proteins,and improves learning and memory in AD mice.
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