Total Flavonoids from Snow Chrysanthemum Exert Synergistic Vascular and Neuroprotective Effects in Hypertensive Vascular Dementia Rats

Background/Objectives: Snow Chrysanthemum (Coreopsis tinctoria Nutt.), a traditional medicinal and edible plant rich in flavonoids (TFSC) with antihypertensive and neuroprotective activities, has unclear effects and mechanisms on vascular dementia (VaD) comorbid with hypertension, a key risk factor accelerating VaD. This study aimed to investigate TFSC’s ameliorative effects on cognitive impairment in hypertensive VaD rats and elucidate its holistic therapeutic mechanisms. Methods: Spontaneously hypertensive rats (SHRs) with unilateral common carotid artery ligation were used to establish the hypertensive VaD model. TFSC was intragastrically administered for 11 weeks. Systolic blood pressure (BP) and cerebral blood flow (CBF) were monitored; cognitive function was assessed via open field, novel object recognition and Morris water maze tests. Histopathological changes were evaluated by H&E and Nissl staining, serum oxidative stress and inflammatory markers were measured, and hippocampal transcriptome sequencing plus RT-qPCR was performed to identify key pathways and genes. Results: The chemical profile of TFSC was characterized, showing a total flavonoid content of 84.96%; 49 compounds were identified, 39 of which were flavonoids. TFSC reduced BP, improved CBF, alleviated cognitive dysfunction and neuronal damage, enhanced antioxidant capacity (increased SOD, CAT, GSH; decreased ROS), and exerted anti-inflammatory effects (reduced TNF-α, IL-1β, IL-6, Ang-II). It modulated multiple pathways, with the PI3K-Akt and MAPK pathways enriched, and validated key differentially expressed genes. Conclusions: This study provides preliminary evidence for the holistic therapeutic potential of TFSC against hypertensive VaD. With integrated vascular regulatory and neuroprotective effects, TFSC serves as a promising candidate for VaD by targeting both vascular risk factors and neuropathological damage.