{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:05:07Z","timestamp":1779195907395,"version":"3.51.4"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007414","name":"Qassim University","doi-asserted-by":"publisher","award":["2025-QU-APC"],"award-info":[{"award-number":["2025-QU-APC"]}],"id":[{"id":"10.13039\/501100007414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Neuroinflammation and oxidative stress play key roles in cognitive decline and memory impairments. This study employed a lipopolysaccharide (LPS)-induced neurotoxicity model and in silico methods, including in silico docking and dynamic simulations, to assess the therapeutic potential of Oxyphenbutazone (OPB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Wistar rats were categorized as control, LPS-only section, LPS\u2009+\u2009OPB receiving low (35\u2009mg\/kg) and high (70\u2009mg\/kg) doses of OPB, and only OPB (70\u2009mg\/kg) doses. Behavioral assessments (Y-maze and Morris water tests) were used to assess cognitive ability. The levels of neuroinflammatory markers [Interleukin-6 (IL-6), IL-1\u03b2, and tumor necrosis factor-alpha (TNF-\u03b1)] and oxidative stress modulators [Superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and malondialdehyde (MDA)] were estimated. Additionally, transforming growth factor-beta (TGF-\u03b2), nuclear factor-kappa B (NF-\u03baB), and inhibitor of kappa B-alpha (I\u03baB-\u03b1) levels were evaluated. In silico analyses, such as molecular docking and dynamic simulations, were used to evaluate the stability of OPB and target molecules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cognitive performance improved after OPB treatment, and the levels of proinflammatory cytokines, antioxidants, TGF-\u03b2, NF-\u03baB, and I\u03baB-\u03b1 were restored. Additionally, in silico analyses illustrated favorable and stable interactions between OPB and the target molecules NF-\u03baB and I\u03baB-\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest the therapeutic potential of OPB in mitigating neurotoxicity and the associated cognitive disabilities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0337611","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:45:16Z","timestamp":1768934716000},"page":"e0337611","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oxyphenbutazone improves memory and learning impairments in LPS-induced neurotoxicity via modulating TGF-\u03b2\/NF-\u03baB\/I\u03baB-\u03b1 pathways: In silico and in vivo study"],"prefix":"10.1371","volume":"21","author":[{"given":"Khalid Saad","family":"Alharbi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2570-3223","authenticated-orcid":true,"given":"Muhammad","family":"Afzal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sattam Khulaif","family":"Alenezi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"ALQahtani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq G.","family":"Alsahli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal","family":"Imam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Kazmi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"2","key":"pone.0337611.ref001","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1365-2567.2009.03225.x","article-title":"Inflammation in neurodegenerative diseases","volume":"129","author":"S Amor","year":"2010","journal-title":"Immunology"},{"issue":"6","key":"pone.0337611.ref002","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1177\/2047487315569401","article-title":"EUROASPIRE IV: a European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries","volume":"23","author":"K Kotseva","year":"2016","journal-title":"Eur J Prev Cardiol"},{"key":"pone.0337611.ref003","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/978-3-319-67144-4_25","article-title":"Rare neurodegenerative diseases: clinical and genetic update.","volume-title":"Rare diseases epidemiology: update and overview","author":"A Matilla-Due\u00f1as","year":"2017"},{"issue":"02","key":"pone.0337611.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21926\/obm.geriatr.2302234","article-title":"Emerging roles of signal transduction pathways in neurodegenerative diseases. 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