{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:37:45Z","timestamp":1792532265030,"version":"4.5.0"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Diabetic nephropathy (DN) is one of the most common and disabling chronic complications of diabetes, with a complex pathogenesis involving genetic susceptibility, inflammatory responses, oxidative stress, and other pathological processes. Current therapeutic approaches can partially control hyperglycemia and slow the decline of renal function, but remain insufficient to reverse established structural damage to the kidneys. This underscores the urgent need for novel, safe, and multi-targeted intervention strategies. In recent years, natural bioactive compounds have attracted considerable attention for their potential in preventing and treating chronic diseases. Quercetin, a natural flavonoid widely distributed in plants, exhibits multiple biological activities\u2014including anti-inflammatory, antioxidant, anti-fibrotic, and cell death\u2013modulating effects\u2014and has shown significant promise in DN therapy. This review provides a comprehensive overview of the major pathogenic mechanisms of DN and recent advances in understanding the regulatory effects of quercetin on key pathological processes. We highlight its potential mechanisms of action, including suppression of inflammation and oxidative stress, inhibition of TGF-\u03b21\u2013mediated renal fibrosis, protection of podocyte function, and induction of ferroptosis, and discuss the possible synergistic interactions among these effects in modulating the DN disease network. In addition, we evaluate the current status and limitations of preclinical research on quercetin, and explore feasible strategies\u2014such as nanoparticle-based delivery systems and structural modification\u2014to enhance its bioavailability and tissue targeting. Finally, we propose future research directions for quercetin-based interventions in DN, aiming to provide a theoretical foundation and novel insights for its clinical translation.<\/jats:p>","DOI":"10.3389\/fphar.2025.1687677","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T05:17:32Z","timestamp":1763011052000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Immunomodulatory roles of quercetin in diabetic nephropathy: targeting inflammation, oxidative stress, and ferroptosis"],"prefix":"10.3389","volume":"16","author":[{"given":"YaFeng","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoNa","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XingJun","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longsheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109781","DOI":"10.1016\/j.cbi.2021.109781","article-title":"The potential therapeutic effects of trifolium alexandrinum extract, hesperetin and quercetin against diabetic nephropathy via attenuation of oxidative stress, inflammation, GSK-3\u03b2 and apoptosis in Male rats","volume":"352","author":"Abdou","year":"2022","journal-title":"Chemico-Biological Interact."},{"key":"B2","doi-asserted-by":"publisher","first-page":"104997","DOI":"10.1016\/j.cellimm.2025.104997","article-title":"Quercetin alleviates diabetic nephropathy by inhibiting M1 macrophage polarization via targeting NLRC5\/NLRP3 pathway","volume":"414","author":"Abudoureyimu","year":"2025","journal-title":"Cell. 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