Fucoxanthin Ameliorates Polycystic Ovary Syndrome by Coordinated Modulation of NF-κB and Nrf2 Signaling: Evidence...

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by aberrant nuclear factor kappa B (NF-κB)-mediated inflammation and impaired nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant defense. This study represents the first investigation of fucoxanthin's concurrent regulatory effects on these opposing signaling axes in PCOS ovarian pathophysiology. Prepubertal female C57BL/6 mice (n = 40; postnatal day 25) were assigned to the following groups: control (sesame oil, 0.1 mL/day subcutaneously, n = 10), dehydroepiandrosterone (DHEA)-induced PCOS (6 mg/100 g body weight in sesame oil, n = 15), or DHEA+fucoxanthin (0.2% w/w in chow, n = 15) for 21 days. Estrous cyclicity was assessed by vaginal cytology. Ovarian morphology used hematoxylin-eosin staining. Serum testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin were measured by enzyme-linked immunosorbent assay. Intraperitoneal glucose/insulin tolerance tests evaluated metabolism. Ovarian malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were quantified. Western blotting analyzed phosphoinositide 3-kinase (PI3K) p85α, protein kinase B (AKT), phospho-AKT, Nrf2, heme oxygenase-1 (HO-1), and NF-κB p65. Fucoxanthin restored estrous cyclicity in 60% of DHEA mice (vs. 0%), increased corpora lutea/large antral follicles, reduced testosterone/LH/IGF-1/insulin (P < 0.05), and elevated FSH/IGFBP-1. Insulin tolerance improved (P < 0.05). Ovarian MDA/TNF-α/IL-1β/IL-6 decreased (P < 0.05); SOD/CAT/T-AOC increased (P < 0.05). Fucoxanthin upregulated PI3K p85α, p-AKT/AKT, Nrf2/HO-1 and downregulated NF-κB p65 (P < 0.05). Collectively, these findings suggest that fucoxanthin coordinately modulates NF-κB suppression and Nrf2/HO-1 activation, establishing a novel multi-targeted therapy for PCOS.