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.
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.
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