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In this study, we investigated the inflammation driven by 12-lipoxygenase (12-LOX)-mediated conversion of arachidonic acid to pro-inflammatory 12-hydroxyeicosatetraenoic acid (12-HETE) and the therapeutic potential of avenanthramide (AVA)-enriched oat extract and trans-resveratrol (RSV) as natural 12-LOX inhibitors. AVA-enriched extract was obtained from oats using 80% methanol, dried, and analyzed by HPLC. Fifty-six rats (3-week-old females) were divided into 8 groups: four received letrozole 1 mg\/kg in 0.5% carboxymethyl cellulose (CMC) for 21 days to induce PCOS, while four received only CMC. Each pair (PCOS and non-PCOS) was treated for 2 weeks with either AVA (100 and 300 mg\/kg), trans-resveratrol (20 mg\/kg), or left untreated. Serum hormonal profile and 12-HETE levels were assessed via ELISA. Ovarian 12-LOX expression was evaluated by Western blotting. Histopathological analysis was performed on the liver and reproductive organs. Treating PCOS-induced rats with 100 mg\/kg AVA, 300 mg\/kg AVA, and 20 mg\/kg RSV significantly restored their hormonal profile to normal levels and significantly reduced ovarian 12-LOX expression and subsequently their serum 12-HETE levels compared to the untreated PCOS rats (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001, and\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001, respectively). The 300 mg\/kg AVA and 20 mg\/kg RSV treatments restored normal ovarian and uterine architecture compared to the untreated PCOS group. No histopathological alterations were observed in the liver or oviduct. Avenanthramides from\n                    <jats:italic>Avena sativa<\/jats:italic>\n                    (oats) restore endocrine and ovarian function in letrozole-induced PCOS by directly inhibiting the redox-sensitive 12-lipoxygenase\u201312-HETE lipid signaling pathway. These findings suggest that avenanthramides may represent a promising therapeutic approach for restoring endocrine balance and ovarian function in PCOS.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-56474-w","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:37:13Z","timestamp":1782121033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Avena sativa-derived avenanthramides suppress 12-lipoxygenase activity and downstream arachidonic acid metabolites in letrozole-induced PCOS rats"],"prefix":"10.1038","volume":"16","author":[{"given":"Yara","family":"Walid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-0337","authenticated-orcid":false,"given":"Raghda A.","family":"Elsabbagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Handoussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar M.","family":"Abdel-Maksoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"issue":"4","key":"56474_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041454","volume":"12","author":"S Singh","year":"2023","unstructured":"Singh, S. et al. 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