Objective To explore the possible mechanism of Xixin Decoction（XXD

洗心汤） in treating Alzheimer′s disease（AD）. Methods Sixty SPF male SD rats were randomly divided into sham operation group

model group

donepezil group

XXD group

and probiotics group

with 12 rats in each group. Except for the sham operation group

rats in the other groups were given intraperitoneal injection of D-galactose and bilateral intraventricular injection of β-amyloid 25-35(Aβ

25-35

) to establish AD rat models. From the 5 th week of modeling

2 ml/d normal saline was given to the sham operation group and the model group by gavage

while donepezil（0.88 mg/kg·d）

XXD（0.94 g/kg·d） and probiotics（30.85 mg/kg·d） were administered in the corresponding medication group by gavage once a day. After 4-week administration

Morris water maze was used to observe the spatial learning and memory ability of rats in each group; HE staining was performed to assess the pathological changes in hippocampal CA1 area; immunohistochemical method was used to detect the expression of β-amyloid 1-42(Aβ

1-42

) in the hippocampus; Western blotting method was used to detect hippocampal brain-derived neurotrophic factor（BDNF）

tyrosine kinase receptor B（TrkB） and colonic BDNF protein expression; 16 S rRNA was tested to detect the diversity and dominant species of the intestinal flora of rats in each group. Results Compared to those of the sham operation group

the escape latency of the model group significantly prolonged; the total swimming distance within 60 s

time spent in target quadrant and the entry times into the effective area significantly decreased; the expression of Aβ

1-42

protein in the hippocampus

the expression of the BDNF and TrkB in the hippocampus tissue and BDNF protein colon tissue also decreased（P

<

0.05 or P

<

0.01）. HE staining showed that the nerve cells in the CA1 area of the hippocampus were arranged disorderly and loosely; cell body shrinkage

cell membrane lysis

nuclear pyknosis and deep staining were found; the normal nerve cells significantly reduced. Compared to those of the model group

the above indicators and hippocampal pathological damage of the XXD group were significantly improved（P

<

0.05 or P

<

0.01）. The 16 S rRNA results showed that the levels of intestinal flora of rats in all groups were dominated by bacteroides

firmicutes and proteobacteria. Compared to the model group

the donepezil group

the XXD group and the probiotics group had significantly increased number of OTUs; the probiotics group had increased firmicutes and acidobacteria phyla; and the donepezil group had increased candida sugar phylum（P

<

0.05 or P

<

0.01）; but there was no significant difference between XXD group and model group（P

>

0.05）. Conclusion XXD can improve the spatial learning and memory ability of AD rats and reduce the deposition of Aβ

1-42

in the hippocampus; the mechanism of action may be related to the increase of neurotrophic factor-related proteins in the brain-gut area and the regulation of intestinal microecology.