Br J Pharmacol. 2026 Oct 20. doi: 10.1111/bph.70645. Online ahead of print.
ABSTRACT
BACKGROUND AND PURPOSE: Vascular dementia (VD) is a cognitive dysfunction syndrome caused by cerebrovascular diseases. Astragalus membranaceus (Fisch.) Bunge (AS) has antioxidative, gut microbiota-regulating, and cognitive-improving effects. Escherichia coli (E. coli) abundance is associated with cognitive dysfunction. This study explored the mechanism by which AS improves VD by regulating E. coli along the gut-brain axis, providing a basis for VD drug research and development.
EXPERIMENTAL APPROACH: VD models were established by permanent ligation of the common carotid artery. Morris water maze, Doppler cerebral blood flow measurement, blood lipid assays, pathological staining, Western blot, and ELISA were used to evaluate AS's protective effects on the brain. 16S rRNA sequencing analyzed gut microbiota to screen differential strains. Metabolomics screened endogenous differential metabolites. Oxygen-glucose deprivation (OGD) was established to evaluate 5-aminovaleric acid effects on neuronal mitochondrial function and oxidative stress.
KEY RESULTS: AS significantly improved cognitive dysfunction, restored cerebral blood flow, and attenuated abnormal protein accumulation and oxidative stress in VD rat brains. Microbiota analysis revealed that AS inhibited E. coli proliferation and mitigated associated pathological damage. Furthermore, endogenous metabolite 5-aminovaleric acid alleviated OGD-induced neuronal damage and oxidative stress.
CONCLUSION AND IMPLICATIONS: AS can treat cognitive dysfunction and brain injury in rodents, regulate gut microbiota balance, and reduce the contribution of E. coli. Meanwhile, AS-regulated endogenous metabolite 5-aminovaleric acid can also treat OGD-induced nerve cell injury. These findings suggest that AS may be a promising candidate for VD treatment and provide mechanistic insight into gut-brain axis regulation.
PMID:42902504 | DOI:10.1111/bph.70645