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This study investigated whether LYC alleviates DEHP-induced brain injury by regulating microglial activation and cGAS-STING signaling. ICR mice were treated with LYC (5 mg\/kg) and\/or DEHP (500 mg\/kg) for 28 days, with results validated in BV2 cells. In vivo, DEHP exposure impaired spatial learning and memory, triggered neuronal degeneration, microglial activation and mitochondrial dysfunction, increased 2\u20323\u2032-cGAMP production, and activated cGAS-STING signaling. LYC supplementation markedly reversed these changes. Network toxicology, molecular docking, and molecular dynamics suggested cGAS as a potential LYC target. In vitro, MEHP-induced M1 polarization was attenuated by LYC, and cGAS silencing verified the pathway\u2019s critical role in LYC\u2019s protection. These findings indicate that LYC alleviates DEHP-induced neural damage by maintaining mitochondrial homeostasis and inhibiting cGAS-STING-mediated microglial activation, providing a potential nutritional strategy for preventing brain damage caused by environmental pollutants.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c07144","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:02:07Z","timestamp":1786701727000},"page":"26071-26086","source":"Crossref","is-referenced-by-count":0,"title":["Lycopene Attenuates\nDEHP-Induced Cerebral Injury by\nSuppressing cGAS-STING-Mediated Microglial Activation"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9858-6553","authenticated-orcid":true,"given":"Muzi","family":"Li","sequence":"first","affiliation":[{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Ma","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Wang","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-9165","authenticated-orcid":true,"given":"Jinlong","family":"Li","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]},{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]},{"name":"Northeast Agricultural University , , 600 Changjiang Street , Xiangfang District, ,","place":["Harbin, P. R. China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"2026090104473408600_cit1","doi-asserted-by":"publisher","first-page":"126664","DOI":"10.1016\/j.envpol.2025.126664","article-title":"Ecotoxicological\neffects of phthalate esters: A review","volume":"382","author":"Xu","year":"2025","journal-title":"Environ.\nPollut."},{"key":"2026090104473408600_cit2","doi-asserted-by":"publisher","first-page":"106228","DOI":"10.1016\/j.envint.2020.106228","article-title":"The impact of Di-(2-ethylhexyl)\nPhthalate and Mono(2-ethylhexyl) Phthalate in placental development,\nfunction, and pathophysiology","volume":"146","author":"Martinez-Razo","year":"2021","journal-title":"Environ. 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