{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T12:30:20Z","timestamp":1783254620254,"version":"3.54.6"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Program of XPCC","award":["2025DB010"],"award-info":[{"award-number":["2025DB010"]}]},{"name":"Science and Technology Program of XPCC","award":["2024ZD025"],"award-info":[{"award-number":["2024ZD025"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82360671"],"award-info":[{"award-number":["82360671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shihezi University International Science and Technology Cooperation Promotion Programme Project","award":["GJHZ202308"],"award-info":[{"award-number":["GJHZ202308"]}]},{"name":"2024 Seventh Division Huyanghe City Fiscal Science and Technology Project","award":["2024A15"],"award-info":[{"award-number":["2024A15"]}]},{"name":"Tianshan Young Talent Scientific and Technological Innovation Team: Innovative Team for Research on Prevention and Treatment of High-incidence Diseases in Central Asia","award":["2023TSYCTD0020"],"award-info":[{"award-number":["2023TSYCTD0020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Excessive fluoride exposure induces developmental neurotoxicity, but effective preventive strategies are currently scarce. Melatonin (Mel), a lipophilic hormone secreted by the pineal gland, exerts antioxidant, anti-inflammatory, and neuroprotective properties. This study aimed to explore Mel\u2019s protective effect and mechanism against fluoride-induced developmental brain injury. We employed a network pharmacology approach to screen the common targets of Mel and fluoride-induced brain injury and performed enrichment analysis. A total of 189 common targets were identified, and these targets were mainly enriched in the HIF-1 signaling pathway and oxidative stress-related pathways. In vivo, Sprague Dawley rats were subjected to perinatal sodium fluoride (NaF) exposure with\/without Mel; in vitro, HT22 cells were subjected to NaF and\/or Mel. The results showed that Mel improved cognitive impairments and alleviated structural damage to hippocampal neurons and mitochondria. Furthermore, Mel upregulated SIRT3 and downregulated HIF-1\u03b1, thereby restoring mitochondrial oxidative phosphorylation and ATP content. This study demonstrates that Mel alleviates fluoride-induced developmental neurotoxicity by improving mitochondrial function through regulating the SIRT3\/HIF-1\u03b1 signaling pathway. This not only offers a novel perspective for elucidating the underlying molecular mechanisms of fluoride-induced developmental neurotoxicity but also provides a theoretical foundation for Mel as a potential protective candidate against fluoride exposure.<\/jats:p>","DOI":"10.3390\/toxics14020128","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:08:57Z","timestamp":1769681337000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Combining Network Pharmacology and Experimental Verification to Investigate the Protective Effect of Melatonin on Fluoride-Induced Brain Injury"],"prefix":"10.3390","volume":"14","author":[{"given":"Runjiang","family":"Ma","sequence":"first","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health 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832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suya","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoxuan","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3465-9789","authenticated-orcid":false,"given":"Qiang","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11083","DOI":"10.1038\/s41598-023-38096-8","article-title":"Prolonged exposure to 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Biosci. (Landmark Ed)"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.freeradbiomed.2023.11.021","article-title":"Enhancement of mitochondrial energy metabolism by Mel promotes vascularized skeletal muscle regeneration in a volumetric muscle loss model","volume":"210","author":"Ge","year":"2024","journal-title":"Free Radic. Biol. 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