Objective

2

To investigate the potential targets of the Chinese medicine compound formula

Buwang Powder

in Alzheimer's disease（AD）through network pharmacology and animal experiments.

Methods

2

Network pharmacology was used to predict potential targets of

Buwang Powder

and AD.Twenty-four male 6-month-old amyloid precursor p

rotein/presenilin 1（APP/PS1）mice were numbered and randomly divided into a model group，a donepezil group， and a

Buwang Powder

group（8 mice per group）using SPSS 25.0 software with a random number table. Eight age-matched male C57BL/6J mice were used as the normal group.The normal and model groups received distilled water（1 mL/100 g body weight） by gavage， the donepezil group received donepezil solution （0.065 mg/mL，1 mL/100 g body weight），and the

Buwang Powder

group received

Buwang Powder

solution （0.936 g/mL，1 mL/100 g body weight），once daily for 1 month.The novel object recognition test and Morris water maze were used to assess learning，spatial memory，and exploratory ability.Hematoxylin-eosin（HE）staining was used to observe the number and morphology of hippocampal neurons.Western blot analysis was performed to detect the expression of phosphatidylinositol 3-kinase（PI3K），protein kinase B（AKT），phosphorylated AKT（p-AKT），glycogen synthase kinase 3β（GSK3β），phosphorylated GSK3β（p-GSK3β），and APP in the hippocampus.

Results

2

Network pharmacology identified multiple active components in

Buwang Powder

， with AKT1（degree=57），PIK3R1（degree=31），and GSK3β（degree=26）as key targets.The signaling pathways associated with

Buwang Powder

in the treatment of AD included the hypoxia-inducible factor-1（HIF-1）pathway，cyclic adenosine monophosphate（cAMP）pathway， and PI3K/AKT signaling pathway. Molecular docking analysis showed strong binding affinity between AKT1 and the main active components of

Buwang Powder

.Animal experiments showed that，compared with the model group，the

Buwang Powder

group had a significantly higher discrimination index in the novel object recognition test（

P

<

0.05），shorter escape latency in the Morris water maze（

P

<

0.05），and a greater number of platform crossings（

P

<

0.05）.HE staining revealed that hippocampal neuro

ns in the

Buwang Powder

group were more densely arranged，more orderly，with clearer nucleoli and more uniform cytoplasmic staining compared with the model group.Western blot results showed that PI3K expression and the ratios of p-AKT/AKT and p-GSK3β/GSK3β were significantly increased in the

Buwang Powder

group（

P

<

0.05），while APP expression was significantly decreased（

P

<

0.05）.

Conclusion

2

Buwang Powder

may improve learning and memory in APP/PS1 mice by regulating the PI3K/AKT/GSK3β signaling pathway，upregulating PI3K，p-AKT，and p-GSK3β expression，downregulating APP expression，and thereby reducing Aβ deposition.