{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:40:31Z","timestamp":1760060431919,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shihezi University Independent Support Project","award":["ZZZC202015A","RCZK201954","CXFZ20218"],"award-info":[{"award-number":["ZZZC202015A","RCZK201954","CXFZ20218"]}]},{"name":"Shihezi University High-level Talent Project","award":["ZZZC202015A","RCZK201954","CXFZ20218"],"award-info":[{"award-number":["ZZZC202015A","RCZK201954","CXFZ20218"]}]},{"name":"Shihezi University Innovation Development Project","award":["ZZZC202015A","RCZK201954","CXFZ20218"],"award-info":[{"award-number":["ZZZC202015A","RCZK201954","CXFZ20218"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objectives: The objectives of this study are to investigate the therapeutic targets and mechanisms of proanthocyanidins in alleviating fluoride-induced liver injury through network pharmacology and animal experimental validation and to explore the medicinal value of grape seed proanthocyanidins. Methods: Potential targets of proanthocyanidins were predicted using databases such as PubChem, SwissTargetPrediction, and GeneCards, and disease-related targets of fluoride-induced liver injury were retrieved to identify common targets between proanthocyanidins and fluoride-induced liver injury. The STRING database was utilized to construct a protein\u2013protein interaction network, and key targets were analyzed for network topology using Cytoscape software. GO and KEGG enrichment analyses were performed on core target genes to explore the potential molecular mechanisms by which proanthocyanidins alleviate fluoride-induced liver injury. The Genes-miRNA interaction network was generated using Networkanalyst, and the molecular docking results between active components and key targets were validated using the CB-Dock2 visualization tool. In the academic context, a rat model of chronic fluoride poisoning was successfully established by means of intragastric administration of sodium fluoride. The protein expression levels of p-mTOR, p-p70s6, p62, LC3-II, and PARP1 in rat liver tissues were detected via Western blot analysis. Results: Network pharmacological analysis successfully identified 96 key genes, through which proanthocyanidins mitigate fluoride-induced liver injury. KEGG enrichment analysis predicted that proanthocyanidins mainly exert their therapeutic effects through the mTOR signaling pathway. The molecular docking results further demonstrated strong binding affinities between proanthocyanidins and key targets, including mTOR and PARP1. The in vivo experimental results indicate that, compared with the control group, the protein expression levels of p-mTOR, p-p70s6k, and p62 in the liver tissues of rats exposed to sodium fluoride significantly increase. Conversely, the protein expression levels of LC3-II and PARP1 significantly decrease (p &lt; 0.05). The outcome of liver intervention with proanthocyanidins is exactly the opposite. Conclusions: Proanthocyanidins can effectively alleviate fluoride-induced liver injury, potentially by regulating the mTOR signaling pathway, autophagy, and apoptosis mechanisms. This study provides valuable insights into the protective effects of proanthocyanidins against fluoride-induced hepatic damage and offers a theoretical basis for further research in this field.<\/jats:p>","DOI":"10.3390\/genes16091037","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T08:28:15Z","timestamp":1756715295000},"page":"1037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identifying Key Genes of Proanthocyanidin Intervention in Fluoride-Induced Liver Injury: Integrated Molecular Docking and Experimental Validation"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhiyu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832002, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, The Xinjiang Production and Construction Corps, Shihezi 832002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832002, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, The Xinjiang Production and Construction Corps, Shihezi 832002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zelin","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832002, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, The Xinjiang Production and Construction Corps, Shihezi 832002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832002, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, The Xinjiang Production and Construction Corps, Shihezi 832002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832002, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, The Xinjiang Production and Construction Corps, Shihezi 832002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiyuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832002, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, The Xinjiang Production and Construction Corps, Shihezi 832002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832002, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, The Xinjiang Production and Construction Corps, Shihezi 832002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.4103\/jpbs.jpbs_929_23","article-title":"Fluoride and its Implications on Oral Health: A Review","volume":"16","author":"Vasisth","year":"2024","journal-title":"J. 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