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, 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.
Conclusions:
YHD could induce autophagy initiation, increase the formation of autophagosomes and
autolysosome, promote the degradation of autophagy substrates, thereby to regulate autophagy, thereby to
promote the clearance of Aβ1-42 to improve memory impairment in SAMP8 mice.
Reply to Nifli, A.-P. Comment on “Rosell-Cardona et al. Dietary Spray-Dried Porcine Plasma Reduces Neuropathological Alzheimer’s Disease Hallmarks in SAMP8 Mice. Nutrients 2021, 13, 2369”
