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We validated its renoprotective effects using high-fat diet\/streptozotocin (HFD\/STZ)-induced diabetic mice and high glucose-stimulated HK-2 cells. Network pharmacology predicted ferroptosis and the NRF2\/HO-1 axis as key targets, which was supported by molecular docking and dynamics simulations indicating stable binding. Mechanistically, OA treatment upregulated the NRF2\/HO-1 pathway, which was associated with the inhibition of ferroptosis\u2500evidenced by suppressed lipid peroxidation and iron overload, improved mitochondrial function, and the regulation of key proteins (e.g., upregulating GPX4 and the iron-storage protein FTH1, while downregulating ACSL4). Its antiferroptotic effects were mimicked by the specific inhibitor Ferrostatin-1 (Fer-1) and abolished by the inducer Erastin (Era). Collectively, this study suggests that OA protects against DN potentially through modulating the NRF2\/HO-1 axis to mitigate ferroptosis, supporting its potential as a promising bioactive dietary compound for the management of DN.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c03675","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:00:32Z","timestamp":1791374432000},"page":"32272-32287","source":"Crossref","is-referenced-by-count":0,"title":["Oleanolic Acid\nAlleviates Diabetic Nephropathy by\nInhibiting Ferroptosis Involving the Activation of the NRF2\/HO-1\nPathway"],"prefix":"10.1021","volume":"74","author":[{"given":"Gongyu","family":"Wu","sequence":"first","affiliation":[{"name":"Mudanjiang Medical University , , , ,","place":["Mudanjiang, Heilongjiang, China, 157011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Mudanjiang Maternal and Child Health Hospital , , ,","place":["Mudanjiang, Heilongjiang, China, 157041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Guan","sequence":"additional","affiliation":[{"name":"Heilongjiang Nursing College , , ,","place":["Harbin, Heilongjiang, China, 150086"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjiu","family":"Gao","sequence":"additional","affiliation":[{"name":"Mudanjiang Medical University , , , ,","place":["Mudanjiang, Heilongjiang, China, 157011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijian","family":"Chen","sequence":"additional","affiliation":[{"name":"Mudanjiang Medical University , , , ,","place":["Mudanjiang, Heilongjiang, China, 157011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Mudanjiang Medical University , , , ,","place":["Mudanjiang, Heilongjiang, China, 157011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuping","family":"Liu","sequence":"additional","affiliation":[{"name":"Mudanjiang Medical University , , , ,","place":["Mudanjiang, Heilongjiang, China, 157011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1113-8525","authenticated-orcid":true,"given":"Huilin","family":"Guan","sequence":"additional","affiliation":[{"name":"Mudanjiang Medical University , , , ,","place":["Mudanjiang, Heilongjiang, China, 157011"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"2026102109083351200_cit1","doi-asserted-by":"publisher","first-page":"1272525","DOI":"10.3389\/fendo.2023.1272525","article-title":"Editorial: The Role of Oxidative Stress and Systemic\nInflammation in Diabetes and Chronic Kidney Disease","volume":"14","author":"Chanda","year":"2023","journal-title":"Front. 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