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Hypertension is one of the growing risk factors for the progression of long-term memory loss. Hypertension-mediated memory loss and treatment remain not thoroughly elucidated to date. Plant-based natural compounds are an alternative solution to treating human diseases without side effects associated with commercial drugs. This study reveals that bioactive peptides extracted from soy hydrolysates mimic hypertension-mediated memory loss and neuronal degeneration and alters the memory molecular pathway in spontaneously hypertensive rats (SHR). The SHR animal model was treated with bioactive peptide VHVV (10 mg/kg/oral administration) and angiotensin-converting-enzyme (ACE) inhibitors (5 mg/kg/oral administration) for 24 weeks. We evaluated molecular level expression of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), and survival markers phospho-protein kinase B (P-AKT) and phosphoinositide 3-kinase (PI3K) after 24 weeks of treatment for SHR in this study. Western blotting, hematoxylin and eosin (H&amp;E) staining, and immunohistochemistry showed long-term memory loss and neuronal degeneration in SHR animals. Bioactive peptide VHVV-treated animals upregulated the expression of long-term memory-relate proteins and neuronal survival. Spontaneously hypertensive rats treated with oral administration of bioactive peptide VHVV had activated CREB-mediated downstream proteins which may reduce hypertension-mediated long-term memory loss and maintain neuronal survival.

Bioactive Peptide VHVV Upregulates the Long-Term Memory-Related Biomarkers in Adult Spontaneously Hypertensive Rats