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Recent studies have shown that the antioxidative stress and anti\u2010inflammatory effects of milk thistle are used in the treatment of neurological diseases. Silibinin has antioxidative stress and antiapoptotic effects and reduces cognitive impairment in models of Alzheimer\u2019s disease (AD). However, the underlying mechanism of silibinin related to improvement of cognition remains poorly understood. In this study, we used the model of lateral ventricle injection of formaldehyde to examine the related mechanism of silibinin in improving cognitive impairment disorders. Oral administration of silibinin for three weeks significantly attenuated the cognitive deficits of formaldehyde\u2010induced mice in a\n                    <jats:italic>Y<\/jats:italic>\n                    \u2010maze test and Morris water maze test.\n                    <jats:italic>Y<\/jats:italic>\n                    \u2010maze results show that silibinin increases the rate of spontaneous response alternation in FA\u2010induced mice. Silibinin increases the target quadrant spending time and decreases escape latency in the Morris water maze test. We examined the effect of silibinin on the NRF2 signaling pathway, and silibinin promoted the nuclear transfer of NRF2 and increased the expression of HO\u20101 but did not significantly increase the protein expression of NRF2 in the hippocampus. Well, silibinin reduces the content of DHE and decreases the levels of apoptosis of mature neuron cells. We investigated the effect of silibinin on the content of formaldehyde degrading enzymes; biochemical analyses revealed that silibinin increased GSH and ALDH2 in formaldehyde\u2010induced mice. In addition, as one of the pathological changes of AD, TAU protein is also hyperphosphorylated in FA model mice. Silibinin inhibits the expression of GSK\u20103\n                    <jats:italic>\u03b2<\/jats:italic>\n                    in model mice, thereby reducing the phosphorylation of TAU proteins ser396 and ser404 mediated by GSK3\n                    <jats:italic>\u03b2<\/jats:italic>\n                    . Based on our findings, we verified that the mechanism of silibinin improving cognitive impairment may be antioxidative stress, and silibinin is one of the potentially promising drugs to prevent formaldehyde\u2010induced cognitive impairment.\n                  <\/jats:p>","DOI":"10.1155\/2022\/5981353","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T19:51:12Z","timestamp":1655409072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Silibinin Ameliorates Formaldehyde\u2010Induced Cognitive Impairment by Inhibiting Oxidative Stress"],"prefix":"10.1155","volume":"2022","author":[{"given":"Pengsheng","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zikun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yebo","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Xu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8517-7969","authenticated-orcid":false,"given":"Ge","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.6b03224"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2016.01.136"},{"key":"e_1_2_15_3_2","first-page":"58","article-title":"Study of necrosis in the liver of formaldehyde and benzo(\u03b1)pyrene exposured-mice","volume":"6","author":"Soni A.","year":"2013","journal-title":"Gene Expression"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2009.06.002"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0344-0338(00)80100-4"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/00039896.1994.9934412"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1204"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.01.139"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1673-5374.2012.05.009"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00065-M"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00015-0"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2005.002"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2011.11.009"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-019-00682-9"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2389-3"},{"key":"e_1_2_15_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.11.045"},{"key":"e_1_2_15_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(98)00331-2"},{"key":"e_1_2_15_18_2","first-page":"573","article-title":"Permeability of the blood-brain barrier to intra-arterial formaldehyde","volume":"102","author":"Shcherbakova L. 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