{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:11:18Z","timestamp":1788480678248,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,23]],"date-time":"2019-06-23T00:00:00Z","timestamp":1561248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-C108-096"],"award-info":[{"award-number":["TSGH-C108-096"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms20123069","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T02:37:40Z","timestamp":1561343860000},"page":"3069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Bioactive Peptide VHVV Upregulates the Long-Term Memory-Related Biomarkers in Adult Spontaneously Hypertensive Rats"],"prefix":"10.3390","volume":"20","author":[{"given":"Da-Tong","family":"Ju","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok Kumar","family":"K.","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-2240","authenticated-orcid":false,"given":"Wei-Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruey-Lin","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-3398","authenticated-orcid":false,"given":"Wan-Teng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hospitality Management, College of Agriculture, Tunghai University, Taichung 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia Hsuan","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Nursing, MeiHo University, Pingtung 912, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Vijaya Padma","family":"Viswanadha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Bharathiar University, Coimbatore 641 046, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Hsiang","family":"Liao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan"},{"name":"Holistic Education Center, Tzu Chi University of Science and Technology, Hualien 970, Taiwan"},{"name":"Cardiovascular research center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-0411","authenticated-orcid":false,"given":"Chih-Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Holistic Education Center, Tzu Chi University of Science and Technology, Hualien 970, Taiwan"},{"name":"Cardiovascular research center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Biotechnology, Asia University, Taichung 413, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.amjcard.2007.05.010","article-title":"Prevention of Stroke in Patients with Hypertension","volume":"100","year":"2007","journal-title":"Am. 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