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Recent studies have highlighted the role of ferroptosis in neuronal death, with elevated peroxide levels being a hallmark of this process. Resveratrol (RSV), a natural compound, has shown promise as a neuroprotective agent. This study explores the potential of RSV in mitigating ferroptosis in PD and elucidates its mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Network pharmacology was employed to predict the interactions between RSV, ferroptosis, and PD\u2010related targets. Cytoscape protein\u2010protein interaction (PPI) analysis identified key potential targets, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses provided insights into the probable mechanisms linking RSV, ferroptosis, and PD. Subsequently, in\u00a0vitro experiments were conducted to validate these findings, followed by in\u00a0vivo studies to confirm the therapeutic efficacy of RSV in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Network pharmacology results indicated that RSV, PD and ferroptosis interact at multiple biological levels. Compared to the PD group, RSV upregulated the expression of SIRT1 and NRF2 and alleviated MPTP\u2010induced motor deficits in mice. Furthermore, RSV reduced levels of MDA, ROS, lipid peroxidation, and cellular iron, while upregulating ferroptosis\u2010negative regulators such as GPX4 and FTH1, as well as pathway indicators like SIRT1 and NRF2. Inhibition of SIRT1 and NRF2 resulted in a decrease in the expression of GPX4\/FTH1 and the SIRT1\/NRF2 signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate that RSV alleviates motor dysfunction in PD by inhibiting ferroptosis through SIRT1\/NRF2 activation, providing novel mechanistic insights into its therapeutic potential for neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70648","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T05:23:26Z","timestamp":1762925006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Groundbreaking Insights Into\n                    <scp>SIRT1<\/scp>\n                    \/\n                    <scp>NRF2<\/scp>\n                    \u2010Mediated Ferroptosis Inhibition by Resveratrol in Parkinson's Disease Models"],"prefix":"10.1111","volume":"31","author":[{"given":"Qian","family":"Zheng","sequence":"first","affiliation":[{"name":"Engineering Research Center for Molecular Medicine, Key Laboratory of Medical Molecular Biology of Guizhou Province, School of Basic Medical Science Guizhou Medical University  Guiyang People's Republic of China"},{"name":"Department of Neurology Affiliated Hospital of Guizhou Medical University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Huang","sequence":"additional","affiliation":[{"name":"Engineering Research Center for Molecular Medicine, Key Laboratory of Medical Molecular Biology of Guizhou Province, School of Basic Medical Science Guizhou Medical University  Guiyang People's Republic of 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