Avena sativa-derived avenanthramides suppress 12-lipoxygenase activity and downstream arachidonic acid metabolites in letrozole-induced PCOS rats

Abstract

Abstract Polycystic ovary syndrome (PCOS) implicates hormonal imbalance, ovulation disorders, metabolic disturbances, and chronic low-grade inflammation. 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 ( P  < 0.001, P  < 0.0001, and P  < 0.0001, 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 Avena sativa (oats) restore endocrine and ovarian function in letrozole-induced PCOS by directly inhibiting the redox-sensitive 12-lipoxygenase–12-HETE lipid signaling pathway. These findings suggest that avenanthramides may represent a promising therapeutic approach for restoring endocrine balance and ovarian function in PCOS.