{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:42:53Z","timestamp":1791380573296,"version":"4.3.3"},"reference-count":74,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T00:00:00Z","timestamp":1739059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32360578"],"award-info":[{"award-number":["32360578"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Bioactive peptides represent a promising therapeutic approach for Alzheimer\u2019s disease (AD) by maintaining cholinergic system homeostasis through the inhibition of acetylcholinesterase (AChE) activity. This study focused on extracting AChE inhibitory peptides from yellowfin tuna pancreas using moderate ultrasound-assisted enzymatic hydrolysis (MUE). Firstly, papain and MUE stood out from five enzymes and four enzymatic hydrolysis methods, respectively, by comparing the degree of hydrolysis and AChE inhibitory activity of different pancreatic protein hydrolysates. Subsequently, the optimal MUE conditions were obtained by single-factor, Plackett\u2013Burman, and response surface methodologies. The pancreatic protein hydrolysate prepared under optimal MUE conditions was then purified by ultrafiltration followed by RP-HPLC, from which a novel AChE inhibitory peptide (LLDF) was identified by LC-MS\/MS and virtual screening. LLDF effectively inhibited AChE activity by a competitive inhibition mechanism, with an IC50 of 18.44 \u00b1 0.24 \u03bcM. Molecular docking and molecular dynamic simulation revealed that LLDF bound robustly to the active site of AChE via hydrogen bonds. These findings provided a theoretical basis for the valuable use of yellowfin tuna pancreas and introduced a new viewpoint on the potential therapeutic advantages of AChE inhibitory peptides for future AD treatment.<\/jats:p>","DOI":"10.3390\/md23020075","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T10:25:57Z","timestamp":1739355957000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Preparation of Acetylcholinesterase Inhibitory Peptides from Yellowfin Tuna Pancreas Using Moderate Ultrasound-Assisted Enzymatic Hydrolysis"],"prefix":"10.3390","volume":"23","author":[{"given":"Pai","family":"Peng","sequence":"first","affiliation":[{"name":"Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Key Laboratory of Seafood Processing of Haikou, School of Food Science and Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"name":"Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Key Laboratory of Seafood Processing of Haikou, School of Food Science and Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiting","family":"Xian","sequence":"additional","affiliation":[{"name":"Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Key Laboratory of Seafood Processing of Haikou, School of Food Science and Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiye","family":"Qu","sequence":"additional","affiliation":[{"name":"Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Key Laboratory of Seafood Processing of Haikou, School of Food Science and Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Marine Science and Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Li","sequence":"additional","affiliation":[{"name":"National R&D Center for Se-Rich Agricultural Products, Processing, Hubei Engineering Research Center for Deep Processing of Green, Se-Rich Agricultural Products, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhou","family":"Zhu","sequence":"additional","affiliation":[{"name":"National R&D Center for Se-Rich Agricultural Products, Processing, Hubei Engineering Research Center for Deep Processing of Green, Se-Rich Agricultural Products, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Key Laboratory of Seafood Processing of Haikou, School of Food Science and Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1002\/alz.076020","article-title":"Ameliorative effect of \u03b2-pinene targeting mitochondrial dysfunction and oxidative stress in Alzheimer\u2019s disease","volume":"19","author":"Dahiya","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/cbdd.14638","article-title":"Recent advances in medicinal chemistry of memantine against alzheimer\u2019s disease","volume":"104","author":"Singh","year":"2024","journal-title":"Chem. 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