{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T23:42:12Z","timestamp":1789342932913,"version":"build-2803163510"},"reference-count":332,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This review covers preclinical studies of stilbene derivative compounds (both natural and synthetic) with potential preventive and therapeutic effects against Alzheimer\u2019s disease (AD). AD is a worldwide neurodegenerative disease characterized by the destruction of nerve cells in the brain and the loss of cognitive function due to aging. Stilbenes are a unique class of natural phenolic compounds distinguished by a C6-C2-C6 (1,2-diphenylethylene) structure and two aromatic rings connected by an ethylene bridge. Stilbenes\u2019 distinct features make them an intriguing subject for pharmacological research and development. Several preclinical studies have suggested that stilbenes may have neuroprotective effects by reducing A\u03b2 generation and oligomerization, enhancing A\u03b2 clearance, and regulating tau neuropathology through the prevention of aberrant tau phosphorylation and aggregation, as well as scavenging reactive oxygen species. Synthetic stilbene derivatives also target multiple pathways involved in neuroprotection and have demonstrated promising biological activity in vitro. However, some properties of stilbenes, such as sensitivity to physiological conditions, low solubility, poor permeability, instability, and low bioavailability, limit their usefulness in clinical applications. To address this issue, current investigations have developed new drug delivery systems based on stilbene derivative molecules. This review aims to shed light on the development of next-generation treatment strategies by examining in detail the role of stilbenes in Alzheimer\u2019s pathophysiology and their therapeutic potential.<\/jats:p>","DOI":"10.3390\/molecules30091982","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T11:00:54Z","timestamp":1745924454000},"page":"1982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Stilbenes Against Alzheimer\u2019s Disease: A Comprehensive Review of Preclinical Studies of Natural and Synthetic Compounds Combined with the Contributions of Developed Nanodrug Delivery Systems"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-7869","authenticated-orcid":false,"given":"Esra","family":"K\u00fcpeli Akkol","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara 06330, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5829-6914","authenticated-orcid":false,"given":"G\u00f6k\u00e7e \u015eeker","family":"Karatoprak","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Erciyes University, Kayseri 38039, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-3043","authenticated-orcid":false,"given":"Berrak","family":"Dumlup\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Faculty of Health Sciences, Istanbul Okan University, \u0130stanbul 34959, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem","family":"Bahad\u0131r Ac\u0131kara","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Ankara University, Ankara 06560, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7058-6711","authenticated-orcid":false,"given":"Reyhan","family":"Ar\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Ankara Medipol University, Ankara 06570, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7i\u011fdem","family":"Y\u00fccel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Erciyes University, Kayseri 38039, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyli Can","family":"Aynal","sequence":"additional","affiliation":[{"name":"Etlik City Hospital, Department of Neurology, Ankara 06170, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-2544","authenticated-orcid":false,"given":"Eduardo","family":"Sobarzo S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda de Materiales, Facultad de Medicina y Ciencias de la Salud, Universidad Central de Chile, Santiago 8330507, Chile"},{"name":"Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"660","DOI":"10.4103\/1673-5374.205108","article-title":"Effects of medicinal plants on Alzheimer\u2019s disease and memory deficits","volume":"12","author":"Akram","year":"2017","journal-title":"Neural Regen Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Koul, B., Farooq, U., Yadav, D., and Song, M. 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