PMID- 31234585 OWN - NLM STAT- MEDLINE DCOM- 20191129 LR - 20231012 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 12 DP - 2019 Jun 23 TI - Bioactive Peptide VHVV Upregulates the Long-Term Memory-Related Biomarkers in Adult Spontaneously Hypertensive Rats. LID - 10.3390/ijms20123069 [doi] LID - 3069 AB - 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&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. FAU - Ju, Da-Tong AU - Ju DT AD - Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. wxyz670628@yahoo.com.tw. FAU - K, Ashok Kumar AU - K AK AD - Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan. ashokbio93@gmail.com. FAU - Kuo, Wei-Wen AU - Kuo WW AUID- ORCID: 0000-0002-2097-2240 AD - Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan. wwkuo@mail.cmu.edu.tw. FAU - Ho, Tsung-Jung AU - Ho TJ AD - Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan. tjho@mail.cmu.edu.tw. FAU - Chang, Ruey-Lin AU - Chang RL AD - School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan. rueylin0112@gmail.com. FAU - Lin, Wan-Teng AU - Lin WT AUID- ORCID: 0000-0001-7700-3398 AD - Department of Hospitality Management, College of Agriculture, Tunghai University, Taichung 407, Taiwan. 040770@thu.edu.tw. FAU - Day, Cecilia Hsuan AU - Day CH AD - Department of Nursing, MeiHo University, Pingtung 912, Taiwan. x00003023@mail.meiho.edu.tw. FAU - Viswanadha, V Vijaya Padma AU - Viswanadha VVP AD - Department of Biotechnology, Bharathiar University, Coimbatore 641 046, India. padma.vijaya@gmail.com. FAU - Liao, Po-Hsiang AU - Liao PH AD - Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan. robert750927@hotmail.com. AD - Holistic Education Center, Tzu Chi University of Science and Technology, Hualien 970, Taiwan. robert750927@hotmail.com. AD - Cardiovascular research center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan. robert750927@hotmail.com. FAU - Huang, Chih-Yang AU - Huang CY AUID- ORCID: 0000-0003-2347-0411 AD - Holistic Education Center, Tzu Chi University of Science and Technology, Hualien 970, Taiwan. cyhuang@mail.cmu.edu.tw. AD - Cardiovascular research center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan. cyhuang@mail.cmu.edu.tw. AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. cyhuang@mail.cmu.edu.tw. AD - Department of Biotechnology, Asia University, Taichung 413, Taiwan. cyhuang@mail.cmu.edu.tw. LA - eng GR - TSGH-C108-096/Tri-Service General Hospital/ PT - Journal Article DEP - 20190623 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Peptides) SB - IM MH - Angiotensin-Converting Enzyme Inhibitors/pharmacology MH - Animals MH - *Biomarkers MH - Blood-Brain Barrier/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cerebral Cortex/drug effects/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Hypertension/drug therapy/etiology/metabolism MH - Immunohistochemistry MH - Memory, Long-Term/*drug effects MH - Neurons/drug effects/metabolism MH - Peptides/chemistry/*pharmacology MH - Rats MH - Rats, Inbred SHR MH - Signal Transduction PMC - PMC6627188 OTO - NOTNLM OT - angiotensin-converting-enzyme inhibitor OT - bioactive peptide OT - blood-brain barrier OT - long-term memory COIS- The authors declare no conflict of interest. EDAT- 2019/06/27 06:00 MHDA- 2019/11/30 06:00 PMCR- 2019/06/01 CRDT- 2019/06/26 06:00 PHST- 2019/04/26 00:00 [received] PHST- 2019/06/20 00:00 [revised] PHST- 2019/06/21 00:00 [accepted] PHST- 2019/06/26 06:00 [entrez] PHST- 2019/06/27 06:00 [pubmed] PHST- 2019/11/30 06:00 [medline] PHST- 2019/06/01 00:00 [pmc-release] AID - ijms20123069 [pii] AID - ijms-20-03069 [pii] AID - 10.3390/ijms20123069 [doi] PST - epublish SO - Int J Mol Sci. 2019 Jun 23;20(12):3069. doi: 10.3390/ijms20123069.