{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:37:29Z","timestamp":1793813849726,"version":"4.6.1"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cobalt exposure, increasingly encountered in industrial and medical contexts, represents a rising neurotoxic threat, yet its underlying mechanisms and effective treatments remain poorly characterized. Here, we investigated the neuroprotective effects of Lyoniresinol, a natural lignan with antioxidant and anti\u2010inflammatory properties, in a rat model of cobalt\u2010induced neurodegeneration. Rats were exposed to cobalt chloride (CoCl\u2082, 40\u2009mg\/kg\/day, intraperitoneally) for 14 days, with a subset receiving co\u2010treatment with Lyoniresinol (30\u2009mg\/kg\/day). Behavioral assessments demonstrated that Lyoniresinol significantly improved spatial memory, recognition memory, anxiety\u2010like behavior, and motor coordination, as evaluated by the Morris water maze, novel object recognition, elevated plus maze, and rotarod test, respectively. Biochemical analyses revealed that Lyoniresinol enhanced antioxidant defense [increased superoxide dismutase (SOD) and reduced glutathione (GSH), reduced Malondialdehyde (MDA)], suppressed pro\u2010inflammatory cytokines [Interlukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1),\n                    <jats:italic>C<\/jats:italic>\n                    \u2010reactive protein (CRP)], and normalized neurotransmitter levels [dopamine, serotonin, and Gamma\u2010aminobutyric acid (GABA)], indicating restored redox homeostasis and neurochemical balance. Histopathological analysis confirmed preservation of hippocampal neuronal architecture in treated animals. Molecular investigations further demonstrated that Lyoniresinol significantly downregulated the overactivation of Nuclear Factor kappa B (NF\u2010\u03baB), Glycogen synthase kinase\u20103 beta (GSK3\u03b2), and c\u2010Jun N\u2010terminal kinase (JNK) signaling pathways at both mRNA and protein levels, as evidenced by qPCR and Western blot analyses. These findings suggest that Lyoniresinol exerts a broad\u2010spectrum neuroprotective effect against cobalt\u2010induced neurotoxicity by concurrently ameliorating behavioral impairments, oxidative and inflammatory stress, neurotransmitter disruptions, and intracellular signaling dysregulation.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70894","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:03:57Z","timestamp":1778742237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lyoniresinol Attenuates Cobalt\u2010Induced Neurobehavioral Deficits and Inflammatory Responses Associated With NF\u2010\u03baB\/GSK3\u03b2\/JNK Signaling in Rats"],"prefix":"10.1002","volume":"40","author":[{"given":"Yuming","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shaanxi Provincial Cancer Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifan","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyao","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Ambulatory Care Management Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8003-173X","authenticated-orcid":false,"given":"Fei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of General Surgery Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429326799241121104310"},{"issue":"4","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.3233\/JAD-200282","article-title":"Heavy Metals Exposure and Alzheimer's Disease and Related Dementias","volume":"76","author":"Bakulski K. M.","year":"2020","journal-title":"Journal of Alzheimer's Disease"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115665240317650240924041923"},{"issue":"10","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.3390\/ani10101855","article-title":"Relationship Between Vitamin B12 and Cobalt Metabolism in Domestic Ruminant: An Update","volume":"10","author":"Gonz\u00e1lez\u2010Monta\u00f1a J. R.","year":"2020","journal-title":"Animals"},{"issue":"10","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1007\/s00204-021-03146-5","article-title":"Cobalt\u2010Induced Oxidative Stress Contributes to Alveolar\/Bronchiolar Carcinogenesis in B6C3F1\/N Mice","volume":"95","author":"Ton T. V. 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A.","year":"2020","journal-title":"Environmental Toxicology and Pharmacology"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2023.131354","article-title":"Cobalt Induces Neurodegeneration Through FTO\u2010Triggered Autophagy Impairment by Targeting TSC1 in an m6A\u2010YTHDF2\u2010dependent Manner","volume":"453","author":"Tang J.","year":"2023","journal-title":"Journal of Hazardous Materials"},{"issue":"5","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1039\/C6FO00138F","article-title":"Enhanced Anti\u2010Oxidative Effect of Fermented Korean Mistletoe Is Originated From An Increase in the Contents of Caffeic Acid and Lyoniresinol","volume":"7","author":"Kim S. Y.","year":"2016","journal-title":"Food & Function"},{"issue":"7","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/ptr.2443","article-title":"Antioxidant and Cytoprotective Compounds From Berberis Vulgaris (Barberry)","volume":"22","author":"Tomosaka H.","year":"2008","journal-title":"Phytotherapy Research"},{"issue":"1","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11010-012-1492-7","article-title":"Lyoniresinol Inhibits Melanogenic Activity Through the Induction of Microphthalmia\u2010Associated Transcription Factor and Extracellular Receptor Kinase Activation","volume":"373","author":"Liu H.","year":"2013","journal-title":"Molecular and Cellular Biochemistry"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115543","article-title":"Lyoniresinol Attenuates Cerebral Ischemic Stroke Injury in MCAO Rat Based on Oxidative Stress Suppression via Regulation of Akt\/GSK\u20103\u03b2\/Nrf2 Signaling","volume":"167","author":"Guo X. 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