Multi-omics reveals the protective mechanisms of Gastrodia elata ethyl acetate extract in vascular dementia.

OBJECTIVE: This study aimed to investigate the ameliorative effect of the ethyl acetate extract of Gastrodia elata (EEGE) on vascular dementia (VD) and its underlying mechanisms. METHODS: A VD rat model was established using the two-vessel occlusion method, while an in vitro cerebral ischemia injury model was constructed by subjecting HT22 cells to oxygen-glucose deprivation. The mechanisms were systematically explored through behavioral tests, ELISA, integrated network analysis, and combined metabolomic and transcriptomic techniques. Key targets were further validated by Western blot. RESULTS: EEGE significantly improved cognitive function in VD rats. Integrated multi-omics and network analysis predicted that its effects involved two key targets, TNF and IGF1, and identified Parishin A and p-hydroxybenzaldehyde as prioritized drug metabolites for assessment. Subsequent experiments confirmed that EEGE effectively downregulated serum levels of IL-6, TNF-α, and IL-1β by modulating the IGF1-TREM2 signaling axis and the AMPK-SIRT1-FoxO1-NF-κB pathway. CONCLUSION: The improvement of cognitive dysfunction in vascular dementia by EEGE is closely associated with its regulation of the IGF1-TREM2 axis and the AMPK-SIRT1-FoxO1-NF-κB pathway, thereby mitigating neuroinflammation. This study provides experimental evidence and a potential mechanistic basis for further exploration of EEGE in VD intervention.