{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:35:49Z","timestamp":1790253349217,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The accumulation of amyloid beta (A\u03b2) and tau tangles in the brain leads to Alzheimer's disease (AD). Fisetin, a natural flavonoid, is an antioxidant molecule, and its neuroprotective effects are not clearly understood. Therefore, attempts have been made to evaluate the neuroprotective effects of fisetin using in silico methods and an A\u03b21\u201042\u2010induced neurotoxicity model in human neuroblastoma SH\u2010SY5Y cells. In silico studies demonstrated that fisetin binds strongly and with high stability to different proteins, such as ULK1 (autophagy marker), p21 (senescence\/cell cycle marker), and synaptophysin (synaptic marker), which are responsible for maintaining brain health and are implicated in AD. Moreover, A\u03b21\u201042 was also found to bind to these protein targets, indicating that A\u03b21\u201042 and fisetin both target common binding sites. In vitro studies on SH\u2010SY5Y cells further confirmed that fisetin promotes cell survival under the toxic effects of A\u03b21\u201042. It reduced oxidative stress and restored the activities of ion channels, which were impaired by A\u03b21\u201042 treatment. Fisetin increased antioxidant defense and restored the activity of molecules that control brain signals. Overall, fisetin acts on multiple targets to protect neurons by reducing oxidative damage, supporting ion channel activity, and inducing the autophagy process.<\/jats:p>","DOI":"10.1002\/jbt.71076","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:00:31Z","timestamp":1786978831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fisetin Attenuates Amyloid\u2010Beta\u2010Induced Neurotoxicity in Human Neuroblastoma SH\u2010SY5Y Cells: Integrating In Silico Target Prediction and In Vitro Validation"],"prefix":"10.1002","volume":"40","author":[{"given":"Charu","family":"Jaiswal","sequence":"first","affiliation":[{"name":"Department of Biotherapeutics Research Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishika","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biotherapeutics Research Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-9898","authenticated-orcid":false,"given":"Abhishek Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biotherapeutics Research Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006338"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5847"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22750"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1400544"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00049"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00255"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00775"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20130134"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.29219\/fnr.v65.6355"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13765"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1480345"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24933"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2025.106110"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prmcm.2024.100547"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.08.052"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0129-3"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0260292"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1984.tb12761.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-017-9746-5"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","unstructured":"Esterbauer\u2014Determination of Aldehydic Lipid Peroxidation Products. Malonaldehyde and 4\u2010Hydroxynonenal\u20141990 | PDF | High Performance Liquid Chromatography | Lipid Peroxidation. Scribd accessed August 22 2025 https:\/\/www.scribd.com\/document\/500653890\/Esterbauer-Determination-of-aldehydic-lipid-peroxidation-products-Malonaldehyde-and-4-hydroxynonenal-1990.","DOI":"10.1016\/0076-6879(90)86134-H"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.11.052"},{"issue":"2","key":"e_1_2_10_25_1","first-page":"130","article-title":"A Modified Spectrophotometric Assay of Superoxide Dismutase","volume":"21","author":"Kakkar P.","year":"1984","journal-title":"Indian Journal of Biochemistry & Biophysics"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087061"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.378"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(96)00423-1"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-025-01772-0"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021125"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05486-1"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2023.1129036"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11080411"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12090846"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.5599\/admet.995"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp300023x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-30380-2_10"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2025.07.013"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1015835"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.04.010"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-13-0064"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm2012563"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111587"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205015"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12081646"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31827b5713"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115672050276594231229050906"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/27694127.2025.2471677"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep07130"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.612078"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.09.015"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.71076","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.71076","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.71076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:43:24Z","timestamp":1789548204000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.71076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":50,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/jbt.71076"],"URL":"https:\/\/doi.org\/10.1002\/jbt.71076","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"2026-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71076"}}