{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:55:53Z","timestamp":1791881753077,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":285,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","award":["N42A660511"],"award-info":[{"award-number":["N42A660511"]}],"id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD) is a major global health challenge characterized by cognitive decline and neuronal degeneration driven by amyloid\u2010\u03b2 (A\u03b2) aggregation and oxidative stress. Given the limited efficacy and adverse effects of current pharmacological therapies, food\u2010derived bioactive compounds have gained increasing attention as potential preventive strategies against neurodegenerative disorders. In this study, we investigated the neuroprotective effects of\n                    <jats:italic>Holothuria leucospilota<\/jats:italic>\n                    extracts using a transgenic\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    model of AD. Our results demonstrated that\n                    <jats:italic>H. leucospilota<\/jats:italic>\n                    hexane extract (HLHE) at 500\u2009\u00b5g\/mL significantly delayed A\u03b2\u2010induced paralysis and improved chemotaxis behavior. Consistently, HLHE treatment reduced A\u03b2 deposition and decreased both high\u2010 and low\u2010molecular weights of A\u03b2 oligomers, as determined by automated Western blot analysis. Additionally, HLHE also reduced reactive oxygen species (ROS) levels. Transcriptomic and RT\u2010qPCR analyses revealed that HLHE enhanced autophagic activity through the upregulation of\n                    <jats:italic>bec-1<\/jats:italic>\n                    (autophagy initiation) and lysosomal genes (\n                    <jats:italic>cpr-1<\/jats:italic>\n                    ,\n                    <jats:italic>cpr-2<\/jats:italic>\n                    , and\n                    <jats:italic>cpr-5<\/jats:italic>\n                    ). Furthermore, HLHE activated antioxidant defense pathways via the insulin\/IGF\u20101 signaling (IIS) axis, specifically upregulating genes associated with SKN\u20101 pathway (\n                    <jats:italic>pmk-1<\/jats:italic>\n                    ,\n                    <jats:italic>skn-1<\/jats:italic>\n                    ,\n                    <jats:italic>gst-4<\/jats:italic>\n                    , and\n                    <jats:italic>gst-10<\/jats:italic>\n                    ) and HSF\u20101 pathway (\n                    <jats:italic>hsf-1<\/jats:italic>\n                    ,\n                    <jats:italic>hsp-16.1<\/jats:italic>\n                    ,\n                    <jats:italic>hsp-12.6<\/jats:italic>\n                    , and\n                    <jats:italic>mtl-1<\/jats:italic>\n                    ). HLHE also promoted nuclear localization of SKN\u20101 and increased expression of its downstream target\n                    <jats:italic>gst-4<\/jats:italic>\n                    . Chemical analysis revealed that HLHE contained arachidonic acid (21.12%) and other bioactive lipid compounds as major constituents, suggesting a synergistic role in promoting autophagy and antioxidant responses. Collectively, this study suggests that HLHE confers neuroprotection against A\u03b2\u2010induced toxicity by activating autophagy and oxidative stress defense mechanisms, supporting its potential development as a food\u2010derived preventive or therapeutic agent for AD.\n                  <\/jats:p>","DOI":"10.1155\/omcl\/1471919","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:40:10Z","timestamp":1791880810000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Role of\n                    <i>Holothuria leucospilota<\/i>\n                    Extract Against Amyloid\u2010\u03b2 Toxicity via Autophagy and Antioxidant Mechanisms in\n                    <i>Caenorhabditis elegans<\/i>\n                    Model"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4905-8240","authenticated-orcid":false,"given":"Chanathip","family":"Kamonnat","sequence":"first","affiliation":[{"name":"Department of Anatomy Faculty of Science Mahidol University  Bangkok 10400 Thailand  mahidol.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7844-2443","authenticated-orcid":false,"given":"Salinthip","family":"Thongdechsri","sequence":"additional","affiliation":[{"name":"Department of Anatomy Faculty of Science Mahidol University  Bangkok 10400 Thailand  mahidol.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-1738","authenticated-orcid":false,"given":"Pichnaree","family":"Kraokaew","sequence":"additional","affiliation":[{"name":"Department of Anatomy Faculty of Science Mahidol University  Bangkok 10400 Thailand  mahidol.ac.th"},{"name":"Department of Anatomy Faculty of Medical Science Naresuan University  Phitsanulok 65000 Thailand  nu.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9786-6024","authenticated-orcid":false,"given":"Nakorn","family":"Niamnont","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science King Mongkut\u2019s University of Technology Thonburi  Bang Mod Bangkok 10140 Thailand  kmutt.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasert","family":"Sobhon","sequence":"additional","affiliation":[{"name":"Department of Anatomy Faculty of Science Mahidol University  Bangkok 10400 Thailand  mahidol.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5700-2646","authenticated-orcid":false,"given":"Krai","family":"Meemon","sequence":"additional","affiliation":[{"name":"Department of Anatomy Faculty of Science Mahidol University  Bangkok 10400 Thailand  mahidol.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.3171\/2018.2.JNS1832"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.937486"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-019-0063-8"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.28"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt187"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/352239a0"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.12.006"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1590\/S1980-57642010DN40400003"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.15.167726"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30403-4"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867330666230112160522"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12010131"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061309"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101271"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/md9101761"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.11.063"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/md21030141"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8047029"},{"key":"e_1_2_12_21_2","volume-title":"Commercially Important Sea Cucumbers of the World","author":"Purcell S. 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