{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:51Z","timestamp":1787029311064,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019345","name":"King Salman Center for Disability Research","doi-asserted-by":"publisher","award":["KSRG-2024-263"],"award-info":[{"award-number":["KSRG-2024-263"]}],"id":[{"id":"10.13039\/501100019345","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Amyloid-\u03b2 (A\u03b2) plaque accumulation, oxidative stress, and cholinergic dysfunction are hallmarks of Alzheimer\u2019s disease (AD), a neurodegenerative disability that progresses over time, ultimately resulting in the loss of neurons. The side effects and limitations of current synthetic drugs have shifted attention toward natural alternatives. This study investigates the ethanolic extract of Aegle marmelos (L.) Corr\u00eaa fruits for their antioxidant, AChE-inhibitory, and anti-amyloidogenic properties, as well as their neuroprotective effects against amyloid beta-peptide (A\u03b21\u201342). Methods: Phytochemical constituents were identified through HR-LCMS analysis and their antioxidant (DPPH, FRAP) and neuroprotective activities (AChE inhibition, ThT binding, MTT assay, ROS reduction, MMP restoration, and AD-related gene expression via qRT-PCR) were assessed using SHSY-5Y neuroblastoma cells. Results: The extract revealed the existence of flavonoids, phenols, and other bioactive substances. In vitro assays demonstrated strong antioxidant and AChE-inhibitory activities, while the ThT binding assay showed protection against amyloid-\u03b2 aggregation. The extract exhibited no cytotoxicity in SHSY-5Y cells, even at a concentration of 500 \u03bcg\/mL, whereas A\u03b21\u201342 at 20 \u03bcM induced significant cytotoxicity. Co-treatment with A\u03b21\u201342 (10 \u03bcM and 20 \u03bcM) and the extract improved cell viability (\u02c350%) and reduced ROS levels. Additionally, the extract restored mitochondrial membrane potential in A\u03b21\u201342 treated cells, highlighting its role in preserving mitochondrial function. Conclusions: These findings suggest that A. marmelos fruits serve as a powerful source of natural antioxidants, AChE inhibitors, and anti-amyloidogenic agents, positioning them as a compelling option for AD treatment.<\/jats:p>","DOI":"10.3390\/ph18040489","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanistic Insights into the Neuroprotective Potential of Aegle marmelos (L.) Correa Fruits against A\u03b2-Induced Cell Toxicity in Human Neuroblastoma SH-SY5Y Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7080-6822","authenticated-orcid":false,"given":"Mohd","family":"Adnan","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il P.O. Box 2440, Saudi Arabia"},{"name":"King Salman Center for Disability Research, Riyadh 11614, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6236-0920","authenticated-orcid":false,"given":"Arif Jamal","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il P.O. Box 2440, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-2763","authenticated-orcid":false,"given":"Fevzi","family":"Bardakci","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il P.O. Box 2440, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-3026","authenticated-orcid":false,"given":"Malvi","family":"Surti","sequence":"additional","affiliation":[{"name":"Research and Development Cell (RDC), Parul University, Waghodia, Vadodara 391760, Gujarat, India"},{"name":"Department of Biotechnology, Parul Institute of Applied Sciences, Parul University, Waghodia, Vadodara 391760, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-7744","authenticated-orcid":false,"given":"Riadh","family":"Badraoui","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il P.O. Box 2440, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-2124","authenticated-orcid":false,"given":"Mitesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Research and Development Cell (RDC), Parul University, Waghodia, Vadodara 391760, Gujarat, India"},{"name":"Department of Biotechnology, Parul Institute of Applied Sciences, Parul University, Waghodia, Vadodara 391760, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","first-page":"e51705","article-title":"Alzheimer\u2019s disease: The past, present, and future of a globally progressive disease","volume":"16","author":"Vejandla","year":"2024","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.25122\/jml-2022-0111","article-title":"Alzheimer\u2019s disease: 120 years of research and progress","volume":"16","author":"Ciurea","year":"2023","journal-title":"J. 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