{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:08:02Z","timestamp":1782490082216,"version":"3.54.5"},"reference-count":72,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Traumatic brain injury (TBI) causes deficits in neurological function, induces pathological changes, and increases oxidative stress. The current investigation aimed to determine Daidzein's neuroprotective potential in experimental TBI. Initially, the HT\u201022 cell line exposed to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> underwent in vitro examination, and the results showed that Daidzein had a neuroprotective effect evident from enhanced cell viability and decreased NO generation. Using three different Daidzein doses\u20141\u2009mg\/kg, 5\u2009mg\/kg, and 10\u2009mg\/kg\u2014in the in vivo experiment, the potential of Daidzein was evaluated against TBI. The neurological severity score (NSS), kondziela's screen test, and elevated plus maze showed improvements after treatment with Daidzein manifested by decreased score, enhanced motor coordination, and anti\u2010anxiety effects. Additionally, Daidzein improved mechanical allodynia and restored the breakdown of the blood\u2010brain barrier. The FTIR spectral analysis showed restoration of the biochemical compositional changes. Furthermore, H &amp; E and Toluidine blue staining revealed an improvement in the histopathological alterations. The RT\u2010qPCR revealed an increase in mRNA expression level of Nrf2, HO\u20101, and Bcl\u20102 and the downregulation of Keap\u20101, Bax and Cleaved caspase\u20103 expressions. Thus, exhibiting its antioxidant and antiapoptotic potential. The RT\u2010qPCR also manifested a decrease in mRNA expression of GFAP and Iba\u20101. Further immunohistochemistry results indicated Daidzein's antioxidant and antiapoptotic properties by upregulating Nrf2 and downregulating cleaved caspase\u20103. Daidzein also lowered the apoptosis index and improved neuronal survival evidenced by flow cytometric analysis. In addition to this, Daidzein notably increased the antioxidant enzyme levels and decreased the oxidative stress markers. The current study's findings point to the neuroprotective potential of the phytoestrogen Daidzein as it lessened neurological abnormalities, decreased oxidative stress, and lowered proapoptotic protein expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbt.70019","type":"journal-article","created":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T05:11:49Z","timestamp":1729314709000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Daidzein ameliorates experimental traumatic brain injury\u2010induced neurological symptoms by suppressing oxidative stress and apoptosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Tehreem","family":"Haider","sequence":"first","affiliation":[{"name":"Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"},{"name":"Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-8470","authenticated-orcid":false,"given":"Salman","family":"Khan","sequence":"additional","affiliation":[{"name":"Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"},{"name":"Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tehmina","family":"Bibi","sequence":"additional","affiliation":[{"name":"Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"},{"name":"Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana Ali","family":"Zahra","sequence":"additional","affiliation":[{"name":"Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"},{"name":"Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussain","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhar ud","family":"Din","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawad Ali","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy Prince Sattam Bin Abdulaziz University Al\u2010Kharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isoo","family":"Youn","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Kyoung","family":"Seo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2019.00006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/NRE-2007-22502"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jnt2040014"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.307.6905.647"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001199-199808000-00003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.08.027"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2010.09.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1132-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.09.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4981"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21360"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00862-y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00208"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0753-0400"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06630.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26102954"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.53388\/TMR20210812240"},{"issue":"5","key":"e_1_2_9_19_1","first-page":"4878","volume":"14","author":"Zhang F.","year":"2017","journal-title":"Exp. Ther. Med"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-012-0508-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23061356"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.11.036"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23137"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.148"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3407"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-020-01434-5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.180749"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2022.100469"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05537-5"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102412472557"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2018.05.001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2015.1080386"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2005.01.011"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot4986"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2017.04.136"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4170156"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117844"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108860"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117684"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26010181"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105211"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2020.05.005"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108777"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00140"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12775"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.05.032"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-010-0055-3"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2019.02.002"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6223"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2012.12.001"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-022-02230-6"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/09638280412331270380"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1997.14.99"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01991-1"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2012.02160.x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000001213"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11070918"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c03285"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00528"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2012.03.005"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126603"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8050680"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.03.018"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4783602"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.2883"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00117"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103087"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759091419899782"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1027-y"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0094"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107562"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147432"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1011740"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T12:06:17Z","timestamp":1731413177000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,18]]},"references-count":72,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/jbt.70019"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70019","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,18]]},"assertion":[{"value":"2024-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70019"}}