Intestinal flora study reveals the mechanism of Danggui Shaoyao San and its decomposed recipes to improve cognitive dysfunction in the rat model of Alzheimer's disease

Background: Alzheimer's disease (AD), characterized by a severe decline in cognitive function, significantly impacts patients' quality of life. Traditional Chinese Medicine (TCM) presents notable advantages in AD treatment, closely linked to its regulation of intestinal flora. Nevertheless, a comprehensive exploration of the precise role of intestinal flora in AD remains lacking. Methods: We induced an AD model through bilateral intracerebroventricular injection of streptozotocin in rats. We divided 36 rats randomly into 6 groups: sham-operated, model, Danggui Shaoyao San (DSS), and 3 DSS decomposed recipes groups. Cognitive abilities were assessed using water maze and open field experiments. Nissl staining examined hippocampal neuron integrity. Western blot analysis determined synaptoprotein expression. Additionally, 16S rDNA high-throughput sequencing analyzed intestinal flora composition. Results: DSS and its decomposed recipe groups demonstrated improved learning and memory in rats (P<0.01). The open field test indicated increased central zone residence time and locomotor activity distance in these groups (P<0.05). Furthermore, the DSS and decomposed recipe groups exhibited reduced hippocampal neuronal damage and increased expression levels of synapsin I (P<0.05) and PSD95 (P<0.01) proteins. Alpha and Beta diversity analyses showed that the intestinal flora species richness and diversity in the DSS and decomposed recipe groups were similar to those in the sham-operated group, signifying a significant restorative effect (P<0.05). Conclusion: The combination of DSS and its decomposed recipes can reduce the abundance of harmful gut microbiota, leading to improvements in cognitive and learning abilities.