[Shenzao Jiannao Oral Liquid treats Alzheimer's disease by regulating gut microbiota].

This study investigates the therapeutic effect and mechanism of Shenzao Jiannao Oral Liquid(SZJN) on Alzheimer's disease(AD) from gut microbiota. APP/PS1 double transgenic mice were used to establish the AD model and then allocated into the following groups: model(normal saline of equal volume), positive drug(donepezil hydrochloride, 0.65 mg·kg~(-1)), and low-, medium-, and high-dose(0.3, 1.5, and 7.5 g·kg~(-1), respectively) SZJN. Meanwhile, C57BL/6J mice of the same brood were selected as the blank group(normal saline of equal volume). All groups were treated by gavage for 8 weeks. The Morris water maze was used to evaluate the spatial exploration, learning, and memory abilities. The nesting test was conducted to assess the daily living abilities. Hematoxylin-eosin(HE) staining was employed to examine histopathological damage in the intestinal tissue. AB-PAS staining was performed to reveal the mucus barrier damage in the intestinal tissue. Western blot was conducted to measure the protein levels of zonula occludens-1(ZO-1) and Occludin. Immunofluorescence(IF) was used to analyze the expression of ZO-1, Occludin, and the macrophage marker F4/80. The diversity, species abundance, and correlations of gut microbiota were analyzed by 16S rDNA sequencing. Animal experiments demonstrated that compared with the model group, the high-dose SZJN group exhibited shortened escape latency, increased platform crossings and time spent in the target quadrant, and improved nesting scores. The high-dose SZJN groups showed alleviated intestinal mucosal contraction, improved cellular morphology, reduced intestinal tissue damage, increased mucin content, and increased goblet cells. Additionally, high-dose SZJN groups exhibited upregulated expression of ZO-1 and Occludin in the intestinal tissue, along with reduced F4/80 protein expression. Gut microbiota analysis revealed increased species diversity and richness in the high-dose SZJN groups, with microbiota structures resembling that in the blank group. These results confirm that high-dose SZJN improves the learning and memory abilities, mitigates intestinal pathological damage, and protects the intestinal tissue of AD mice by regulating the gut microbiota.