{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:28:59Z","timestamp":1785403739044,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009108","name":"Shandong University","doi-asserted-by":"publisher","award":["ts20250105"],"award-info":[{"award-number":["ts20250105"]}],"id":[{"id":"10.13039\/100009108","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ts20250105"],"award-info":[{"award-number":["ts20250105"]}],"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004032","name":"Jilin University","doi-asserted-by":"publisher","award":["X202610183270"],"award-info":[{"award-number":["X202610183270"]}],"id":[{"id":"10.13039\/501100004032","id-type":"DOI","asserted-by":"publisher"}]},{"award":["X202610183270"],"award-info":[{"award-number":["X202610183270"]}],"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chronic exposure to lead (Pb) represents a persistent environmental hazard that can impair hippocampal integrity and cognitive function, while effective protective strategies remain limited. Ginsenoside Rg1 is an important bioactive constituent derived from Panax ginseng and has been reported to possess antioxidant and neuroprotective activities; however, its involvement in Pb-triggered ferroptosis-associated neuronal damage remains unclear. In the present study, a male C57BL\/6J mouse model of subchronic lead acetate exposure and a lead-exposed HT22 cell model were established. Behavioral and histopathological changes were assessed, followed by analysis of inflammatory responses, oxidative stress, ferroptosis-related alterations, and Nrf2-associated signaling. Rg1 improved cognitive performance and attenuated hippocampal neuronal loss, neuroinflammatory activation, oxidative injury, and ferroptosis-related alterations, including ferrous ion accumulation and mitochondrial damage. Consistently, Rg1 restored SLC7A11\/xCT and GPX4 expression and enhanced Nrf2-associated antioxidant signaling, whereas the Nrf2 inhibitor ML385 weakened the Rg1-induced increases in nuclear Nrf2, NQO1, and GPX4. Collectively, these findings indicate that Rg1 alleviates lead-induced neurotoxicity and support the involvement of Nrf2 signaling in the regulation of oxidative stress and ferroptosis-related injury. These findings provide experimental evidence supporting further preclinical investigation of Rg1 and its Nrf2-associated neuroprotective mechanisms in Pb-induced neuronal injury.<\/jats:p>","DOI":"10.3390\/molecules31152559","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"2559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Rg1 Alleviates Lead-Induced Neurotoxicity Through Nrf2-Associated Modulation of Oxidative Stress and Ferroptosis"],"prefix":"10.3390","volume":"31","author":[{"given":"Yiyao","family":"Gong","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-2021","authenticated-orcid":false,"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7026-3795","authenticated-orcid":false,"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Advanced Medical Research Institute, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0564-4265","authenticated-orcid":false,"given":"Li","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e831","DOI":"10.1016\/S2542-5196(23)00166-3","article-title":"Global health burden and cost of lead exposure in children and adults: A health impact and economic modelling analysis","volume":"7","author":"Larsen","year":"2023","journal-title":"Lancet Planet. 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