Perillaldehyde reduces mitochondrial oxidative stress damage by regulating KCNT2/NR1D1 protein activity in vascular dementia rats.

Abstract

<p>BACKGROUND: This study explores the therapeutic potential of perillaldehyde (PAE) in a rat model of vascular dementia (VD), focusing on its effects on cognitive function, neuronal morphology, cell proliferation, apoptosis, oxidative stress, and mitochondrial function. METHODS AND RESULTS: Thirty-two male Sprague-Dawley rats were divided into four groups: control, PAE treatment, VD model, and VD + PAE combined. Morris water maze results showed that PAE improved spatial learning and memory, reducing escape latency by 46.2% and increasing target quadrant time by 58.7%. HE and Golgi staining indicated increased dendrite length and spine density by 39.5% and 42.1%. Immunohistochemistry showed a 2.3-fold increase in neuronal proliferation, and TUNEL staining revealed a 55% reduction in apoptosis. PAE also reduced oxidative stress, lowering NOX2/NOX4 expression by 45%, decreasing MDA by 37%, and increasing SOD and GSH by 52% and 48%, respectively. Mitochondrial function was improved, with enhanced membrane potential and reduced Drp1 and FIS1 expression. At the molecular level, PAE upregulated KCNT2 and NR1D1 proteins and inhibited PI3K and JNK pathways. CONCLUSIONS: In conclusion, PAE alleviates mitochondrial oxidative stress and neuronal damage via the KCNT2/NR1D1 pathway, showing promise for treating vascular dementia.</p>