Chronic cerebral hypoperfusion (CCH) causes progressive cognitive impairment due to low cerebral blood flow (CBF). Yangxue Qingnao granules (YXQNG) exert blood-tonifying effects. We investigated its effects and mechanisms on cognitive impairment in a CCH rat model.

CCH was induced in rats by bilateral common carotid artery occlusion (BCCAO). YXQNG was administered daily via intragastric gavage for 42 days. Laser speckle imaging was used to evaluate changes in CBF. The Morris water maze (MWMT) and open field (OFT) tests were performed to evaluate cognitive function and motor and exploration abilities. Hematoxylin and eosin (HE) staining was used to assess neuronal damage. Proteomic analysis of the cerebral cortex and hippocampus was used to investigate differentially expressed proteins (DEPs).

Five YXQNG compounds were identified: paeoniflorin, albiflorin, ferulic acid, senkyunolide Ⅰ, and rosmarinic acid. YXQNG increased CBF, improved spatial memory and motor/exploration abilities, and reduced neuronal damage in cortex and hippocampus. Proteomic analysis revealed 98 cortical and 162 hippocampal DEPs in the CCH model that were regulated by YXQNG. GO and KEGG enrichment analysis suggested that YXQNG may improve synaptic plasticity and regulate lipid metabolism. Protein-protein interaction analysis found close connectivity between Mrps16, Dmgdh, Xylb, and Rgn in the hippocampus, indicating that YXQNG may alleviate neuronal injury and enhance synaptic plasticity.

YXQNG treatment alleviates neuron injury in the cortex and hippocampus, and improves cognitive impairment in rats after CCH. These effects are mediated by improved synaptic plasticity and regulation of lipid metabolism.