{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:48:49Z","timestamp":1787064529398,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2019YFC1711000"],"award-info":[{"award-number":["2019YFC1711000"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Joint Fund for Science and Technology Research and Development of Henan Province","award":["245101610085"],"award-info":[{"award-number":["245101610085"]}]},{"name":"the Science and Technology Development Plan of Henan Province","award":["242102310430"],"award-info":[{"award-number":["242102310430"]}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"crossref","award":["262300422195"],"award-info":[{"award-number":["262300422195"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a common neurodegenerative disorder linked to cholinergic dysfunction, with butyrylcholinesterase (BChE) being a key therapeutic target for moderate\u2013severe AD. Cortex Mori Radicis, a traditional Chinese medicinal herb, is rich in Diels\u2013Alder adducts with potential neuroprotective effects; here, eighteen Diels\u2013Alder adducts (four new: morusalbanol B\u2013E, 1\u20134) were isolated and identified from its 80% ethanol extract. Their cholinesterase inhibitory activities were assessed via Ellman\u2019s method, with enzyme kinetics and molecular docking performed for active compounds. Most compounds showed selective BChE inhibition, with kuwanon X (14) being the most potent (IC50 = 2.3 \u03bcM). morusalbanol B (1), cathayanon A (8), and kuwanon G (12) acted as noncompetitive inhibitors, while Morusalbanol C (2) and kuwanon X (14) were mixed competitive inhibitors. Molecular docking suggested that potent inhibitors occupied the BChE active pocket via hydrogen bonds, \u03c0-\u03c0 stacking, and hydrophobic interactions with Trp82, His438, and Phe329. MD simulations and MM-GBSA binding free energy analysis further verified that all three representative complexes (1, 8, and 14) achieved favorable thermodynamic and structural stability, with binding driven primarily by van der Waals forces. Residue decomposition revealed that Trp82 and Phe329 served as core binding hotspots for all tested inhibitors. Structure\u2013activity analysis indicated that a cis-trans methylcyclohexene configuration, shorter aliphatic ester chains, and more prenyl groups enhanced BChE inhibition. This study provides new lead compounds and a systematic molecular mechanism basis for developing novel anti-AD BChE inhibitors from natural products.<\/jats:p>","DOI":"10.3390\/molecules31101574","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:35:43Z","timestamp":1778528143000},"page":"1574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phytochemical Profiling of Mulberry Diels-Alder Adducts as Selective Butyrylcholinesterase Inhibitors: In Vitro Activity, Molecular Docking, and Molecular Dynamics Simulation"],"prefix":"10.3390","volume":"31","author":[{"given":"Xiang","family":"Cui","sequence":"first","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Cheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Qi","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6680-5632","authenticated-orcid":false,"given":"Yun-Xia","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-7523","authenticated-orcid":false,"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ru","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-8532","authenticated-orcid":false,"given":"Chang-Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Field Observation and Research Station of Green Agriculture in Dancheng County, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122253","DOI":"10.1016\/j.eswa.2023.122253","article-title":"In-house data adaptation to public data: Multisite MRI harmonization to predict Alzheimer\u2019s disease conversion","volume":"238E","author":"Park","year":"2024","journal-title":"Expert Syst. 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