{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:07:23Z","timestamp":1790849243042,"version":"4.1.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Ovarian Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Polycystic ovary syndrome (PCOS), a common endocrine-metabolic disorder, is driven by hyperandrogenism and chronic low-grade inflammation that impair follicular development. Granulosa cell pyroptosis is increasingly recognized as a key pathogenic mechanism in PCOS.\n                      <jats:italic>Luteolin<\/jats:italic>\n                      (LUT), a natural flavonoid found in many traditional medicinal plants, exhibits potent anti-inflammatory properties. However, its role in regulating granulosa cell pyroptosis within the context of PCOS has not been elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a dehydroepiandrosterone (DHEA)-induced PCOS rat model to evaluate LUT\u2019s therapeutic effects. Hormone and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), while network pharmacology and molecular docking were used to predict molecular targets. In vitro, dihydrotestosterone (DHT)-treated KGN cells served as a model for granulosa cell dysfunction. Pyroptosis was assessed by Cell Counting Kit\u22128 (CCK-8), lactate dehydrogenase (LDH) release, and transmission electron microscopy. The expression and activation of androgen receptor (AR), Signal Transducer and Activator of Transcription 3 (STAT3), and NOD-like Receptor Pyrin domain-containing protein 3 (NLRP3) inflammasome components were analyzed by Western blot and immunohistochemistry, with their roles confirmed using specific inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Luteolin (LUT) treatment alleviated hormonal imbalance and ovarian morphological abnormalities in PCOS rats. LUT suppressed STAT3 phosphorylation, pro-inflammatory cytokine expression, and NLRP3 inflammasome activation in both in vivo and in vitro models. Network pharmacology identified STAT3 as a high-affinity target of LUT (binding energy: \u2212\u20098.589\u00a0kcal\/mol). Mechanistically, LUT attenuated granulosa cell pyroptosis by suppressing the AR\/STAT3\/NLRP3 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Luteolin inhibits androgen-induced granulosa cell pyroptosis by targeting the AR\/STAT3\/NLRP3 signaling pathway. These findings provide a robust mechanistic basis for luteolin\u2019s therapeutic potential in PCOS, supporting its development as a targeted therapy for this and other inflammatory reproductive disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13048-025-01952-4","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T08:45:26Z","timestamp":1769244326000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Luteolin alleviates PCOS by inhibiting AR\/STAT3\/NLRP3-mediated granulosa cell pyroptosis"],"prefix":"10.1186","volume":"19","author":[{"given":"Xiaoling","family":"Ouyang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobai","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"issue":"3","key":"1952_CR1","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s00404-024-07607-x","volume":"310","author":"N Salari","year":"2024","unstructured":"Salari N, Nankali A, Ghanbari A, Jafarpour S, Ghasemi H, Dokaneheifard S, et al. Global prevalence of polycystic ovary syndrome in women worldwide: a comprehensive systematic review and meta-analysis. Arch Gynecol Obstet. 2024;310(3):1303\u201314.","journal-title":"Arch Gynecol Obstet"},{"issue":"1","key":"1952_CR2","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/humrep\/deh098","volume":"19","author":"EA-SP Rotterdam","year":"2004","unstructured":"Rotterdam EA-SP. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41\u20137.","journal-title":"Hum Reprod"},{"issue":"9","key":"1952_CR3","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/S2213-8587(22)00163-2","volume":"10","author":"AE Joham","year":"2022","unstructured":"Joham AE, Norman RJ, Stener-Victorin E, Legro RS, Franks S, Moran LJ, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022;10(9):668\u201380.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"1952_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020583","author":"HM Sadeghi","year":"2022","unstructured":"Sadeghi HM, Adeli I, Calina D, Docea AO, Mousavi T, Daniali M, et al. Polycystic ovary syndrome: a comprehensive review of pathogenesis, management, and drug repurposing. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms23020583.","journal-title":"Int J Mol Sci"},{"key":"1952_CR5","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaad035","author":"Y Chen","year":"2023","unstructured":"Chen Y, Miao C, Zhao Y, Yang L, Wang R, Shen D, et al. Inflammasomes in human reproductive diseases. 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Luteolin inhibits inflammation and M1 macrophage polarization in the treatment of Pseudomonas aeruginosa-induced acute pneumonia through suppressing EGFR\/PI3K\/AKT\/NF-kappaB and EGFR\/ERK\/AP-1 signaling pathways. Phytomedicine. 2025;141:156663.","journal-title":"Phytomedicine"},{"key":"1952_CR15","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9966750","volume":"2022","author":"M Chagas","year":"2022","unstructured":"Chagas M, Behrens MD, Moragas-Tellis CJ, Penedo GXM, Silva AR, Goncalves-de-Albuquerque CF. Flavonols and flavones as potential anti-inflammatory, antioxidant, and antibacterial compounds. Oxid Med Cell Longev. 2022;2022:9966750.","journal-title":"Oxid Med Cell Longev"},{"key":"1952_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/nu14061155","author":"S Caporali","year":"2022","unstructured":"Caporali S, De Stefano A, Calabrese C, Giovannelli A, Pieri M, Savini I, et al. 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Bisphenol A-induced ovarian damage countered by luteolin: experiments in in vitro CHO cells and in vivo PCOS phenotype zebrafish. Tissue Cell. 2024;91:102532.","journal-title":"Tissue Cell"},{"issue":"6","key":"1952_CR19","doi-asserted-by":"publisher","first-page":"E1085","DOI":"10.1152\/ajpendo.00034.2021","volume":"320","author":"Y Huang","year":"2021","unstructured":"Huang Y, Zhang X. Luteolin alleviates polycystic ovary syndrome in rats by resolving insulin resistance and oxidative stress. Am J Physiol Endocrinol Metab. 2021;320(6):E1085\u201392.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"1952_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118279","volume":"331","author":"XK Shi","year":"2024","unstructured":"Shi XK, Peng T, Azimova B, Li XL, Li SS, Cao DY, et al. 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