Background: Studies have found that autophagy could promote the clearance of Aβ. To
promote and maintain the occurrence of autophagy in Alzheimer's Disease (AD) might be a potential
way to reduce neuronal loss and improve the learning and memory of AD.
Objective: To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model.
Methods: Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and
YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically
administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water
for P8 group and R1 group. Morris Water Maze (MWM) test, Nissl’s staining, TEM, TUNEL staining,
immunofluorescence double staining, and western blot analysis were applied to learning and
memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aβ, LAMP1, and
autophagy related proteins.
Results: The escape latency time of YHD group was significantly shorter on the 4th and 5th day during
MWM test than those in P8 group (P=0.011, 0.008<0.05), and the number of crossing platform in YHD
group increased significantly (P=0.02<0.05). Nissl’s staining showed that the number of neurons in
YHD group increased significantly (P<0.0001). TEM showed in YHD group that the nucleus of neurons
was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and
membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically
significant difference (P=0.093>0.05), while Caspase3 expression in YHD group was significantly
lower (P=0.044<0.05). YHD could promote the clearance of Aβ1-42 protein, improve the expression
of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins.
Conclusion: YHD could induce autophagy initiation, increase the formation of autophagosomes and
autolysosome, promote the degradation of autophagy substrates, thereby regulating autophagy, and
promoting the clearance of Aβ1-42 to improve memory impairment in SAMP8 mice.