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We find that captopril failed to protect against synaptic damage in spontaneously hypertensive rats. In contrast, the hazelnut-derived peptide YYLLVR exerted a dual-modulating effect by activating Angiotensin-converting enzyme 2 (ACE2), simultaneously lowering blood pressure and ameliorating cognitive impairment. YYLLVR reduced mean arterial pressure by 43.18 mmHg (60 mg\/kg body weight per day for 4 weeks, P &amp;lt; 0.05). In behavioral tests, it reduced escape latency by 11.29 s and alleviated hippocampal neuronal damage (P &amp;lt; 0.05). YYLLVR inhibited ACE, activated ACE2, suppressed neuroinflammation via glial inactivation, reduced pathological p-tau, and enhanced synaptic plasticity. It also ameliorated mitochondrial dysfunction and oxidative stress across multiple cell lines (100 \u03bcM). Molecular dynamics confirmed stable binding of YYLLVR to ACE2. This study establishes a nutritional intervention framework for ACE2-activating peptides against hypertension-induced cognitive impairment.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c06355","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:58:58Z","timestamp":1784041138000},"page":"22889-22907","source":"Crossref","is-referenced-by-count":1,"title":["Activation of ACE2\nby Hazelnut-Derived Peptide YYLLVR:\nA Novel Strategy against Hypertension-Induced Cognitive Impairment"],"prefix":"10.1021","volume":"74","author":[{"given":"Wentian","family":"Song","sequence":"first","affiliation":[{"name":"Zhejiang A&F University , , , ,","place":["Hangzhou, Zhejiang, China, 311300"]},{"name":"Zhejiang A&F University , , , ,","place":["Hangzhou, Zhejiang, China, 311300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Shen","sequence":"additional","affiliation":[{"name":"Jilin Agricultural University , , ,","place":["Changchun, China, 130118"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9184-7925","authenticated-orcid":true,"given":"Dan","family":"Wu","sequence":"additional","affiliation":[{"name":"Jilin Agricultural University , , ,","place":["Changchun, China, 130118"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7074-8618","authenticated-orcid":true,"given":"Xiaoting","family":"Liu","sequence":"additional","affiliation":[{"name":"Jilin Agricultural University , , ,","place":["Changchun, China, 130118"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Liu","sequence":"additional","affiliation":[{"name":"Jilin Agricultural University , , ,","place":["Changchun, China, 130118"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-2104","authenticated-orcid":true,"given":"Weihong","family":"Min","sequence":"additional","affiliation":[{"name":"University of Shanghai for Science and Technology , , ,","place":["Shanghai, China, 200093"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026072910075389800_cit1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408811","article-title":"ZFP36 Regulates Vascular Smooth Muscle Contraction\nand Maintains Blood Pressure","volume":"12","author":"Cui","year":"2025","journal-title":"Adv. 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