Luteolin modulates the TGFB1/PI3K/PTEN axis in hormone-induced uterine leiomyomas: Insights from a rat model

Abstract

Uterine leiomyomas (UL), or fibroids, are non-cancerous tumors of the uterine smooth muscle, affecting approximately 70% of women of reproductive age. They are the most prevalent solid tumors in the gynecological tract and a major indication for hysterectomy. The pathogenesis of UL involves uterine inflammation, uncontrolled cell division, and suppressed apoptosis. This study evaluated the protective effects of luteolin, a flavonoid known for its anti-inflammatory and antioxidant properties, against diethylstilbestrol and progesterone-induced UL in female rats. Twenty-four female Wistar rats were divided into four groups: (1) control, (2) luteolin (10 mg/kg, PO), (3) UL (diethylstilbestrol 1.35 mg/kg + progesterone 1 mg/kg, SC), and (4) UL + luteolin (10 mg/kg). The treatment duration was five weeks. Histological analyses were performed using hematoxylin and eosin (H&E) staining and Masson's Trichrome staining to evaluate uterine architecture and fibrosis. Histological results demonstrated normal uterine architecture in the control and luteolin groups, with marked neoplastic cell proliferation and fibrosis in the UL group, significantly mitigated by luteolin treatment. Luteolin reduced uterine weights and exhibited antioxidant, anti-inflammatory, pro-apoptotic, and anti-proliferative effects. Immunohistochemical analysis revealed that luteolin significantly reduced α-SMA protein expression, suggesting its role in modulating fibrotic pathways by inhibiting TGF-β1 and PI3K and enhancing PTEN production. These findings highlight luteolin's potential as a non-invasive therapeutic option for UL and suggest the need for further clinical studies to establish its efficacy, optimize dosage, and evaluate its safety profile in humans.