Multi-target neuroprotective effects of Yukgunja-Tang (Liujunzi Decoction) in a mouse model of vascular dementia: Behavioral, glial, and transcriptomic evidence.

This study aimed to evaluate the neuroprotective effects of Yukgunja-Tang (Liujunzi Decoction, YGJT) in a bilateral common carotid artery stenosis (BCAS)-induced mouse model of vascular dementia and to explore its potential as a multi-target intervention. Male C57BL/6 mice were subjected to BCAS to induce vascular dementia and were divided into sham-operated, BCAS control, YGJT 40 mL/kg, and YGJT 80 mL/kg groups. YGJT or distilled water was administered orally three times per week for six weeks, starting two weeks after surgery. Cognitive function was assessed using the Y-maze test and the novel object recognition test (NORT). Astrocytic and microglial activation were evaluated by immunofluorescence staining, and transcriptomic changes were analyzed using RNA sequencing. In the NORT, the YGJT 80 mL/kg group demonstrated a significant improvement in BCAS-induced cognitive impairment compared with the BCAS control group. Immunofluorescence analysis demonstrated a significant reduction in microglial activation in the cerebral cortex and white matter following YGJT treatment. RNA sequencing revealed that approximately 70.1% of genes dysregulated by BCAS surgery were restored toward baseline expression levels in the YGJT 80 mL/kg group. Protein-protein interaction network analysis identified several hub proteins, including plasminogen (Plg), caspase-1 (Casp1), cluster of differentiation 36 (CD36), C-X-C motif chemokine receptor 5 (Cxcr5), cluster of differentiation 14 (CD14), and cytochrome P450 family 2 subfamily C member 29 (Cyp2c29). These findings suggest that YGJT may be a multi-component intervention associated with changes in neuroinflammatory and transcriptomic patterns under chronic cerebral hypoperfusion, and may have potential relevance for the management of vascular cognitive impairment.