Mechanism analysis of Tongqiao Yizhi decoction in treating vascular dementia rats by brain tissue untargeted metabonomics and fecal 16S rRNA gene sequencing.

Objective: To analyze the mechanism of Tongqiao Yizhi decoction (TQYZD, ) in treating vascular dementia (VaD) rats using brain tissue untargeted metabonomics and fecal 16S rRNA gene sequencing.

Methods: The chemical composition of TQYZD was analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry. The effects of TQYZD on VaD rats were evaluated by water maze test, hematoxylin-eosin staining, enzyme-linked immunosorbent assay and Western blot. Untargeted metabolomics and 16S rRNA sequencing were utilized to explore the relationship between metabolic profiles and the structure and function of intestinal flora. Fecal microbiota transplantation (FMT) was used to validate the role of gut microbiota in VaD. Spearman correlation analysis of differential metabolites and gut microbiota was performed.

Results: The results showed that TQYZD improved cognitive function and neuronal damage in VaD rats, and reduced inflammatory response and repaired the intestinal barrier. In addition, TQYZD had the effect of modulating gut microbes in VaD rats, and FMT further confirmed that gut flora plays an important role in TQYZD treatment of VaD. Untargeted metabolomics revealed that VaD could lead to metabolic disorders in brain tissues, and TQYZD significantly altered the metabolites of brain tissues in Middle Cerebral Artery Occlusion rats. The results of spearman correlation analysis showed that there was a significant correlation between intestinal flora and the metabolites of brain tissues.

Conclusion: In this study, we demonstrated that TQYZD can improve metabolic disorders in vascular dementia rats by acting on intestinal flora.