Glangin Mitigates the PI3K/pAKT/PTEN Axis in Letrozole-Induced Polycystic Ovary Syndrome: Insights From a Rat Model

Author(s)

Lenah S. Binmahfouz, MSc, PharmD, PhD.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder affecting up to 13% of reproductive-aged women, marked by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Conventional pharmacologic therapies often produce adverse effects, prompting interest in safer alternatives. This study investigated the protective effects of galangin, a flavonoid with antioxidant and anti-inflammatory properties, in a letrozole-induced PCOS rat model.
METHODS: Thirty-six adult female Wistar rats were randomized into six groups (n=6): (1) control, (2) galangin (8 mg/kg), (3) letrozole (1 mg/kg), (4) letrozole + galangin (4 mg/kg), (5) letrozole + galangin (8 mg/kg), and (6) letrozole + metformin (200 mg/kg). Treatments were given orally once daily for 21 days. Ovarian histology, serum hormone levels (estradiol, LH, AMH), oxidative stress markers (MDA, SOD, CAT, GSH), and immunohistochemical profiles were assessed. One-way ANOVA with Tukey’s test was used for statistical analysis (p<0.05).
RESULTS: Letrozole-induced PCOS rats showed follicular atresia and granulosa cell vacuolation, alongside reduced estradiol and elevated LH and AMH (p<0.05). Galangin, especially at 8 mg/kg, improved ovarian morphology and normalized hormone levels. It reduced MDA by 48% and increased SOD, CAT, and GSH by 228%, 210%, and 250%, respectively (p<0.05). Inflammatory markers (IL-6, TNF-α, NF-κB) were significantly lowered by 91%, 81%, and 87%, respectively (p<0.05). Galangin also modulated the PI3K/pAKT/PTEN axis, increasing PI3K and pAKT while downregulating PTEN (p<0.05), indicating improved cellular signaling and follicular regulation.
CONCLUSIONS: Galangin exerts protective effects in letrozole-induced PCOS by alleviating oxidative stress, hormonal imbalance, and inflammation, while preserving ovarian histoarchitecture. These findings support its potential as a complementary therapy in PCOS management.

Conference/Value in Health Info

2025-11, ISPOR Europe 2025, Glasgow, Scotland

Value in Health, Volume 28, Issue S2

Code

EPH115

Topic

Epidemiology & Public Health, Medical Technologies, Patient-Centered Research

Topic Subcategory

Public Health

Disease

Diabetes/Endocrine/Metabolic Disorders (including obesity), Reproductive & Sexual Health

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