Amygdalin (Vitamin B17) as a Natural Bioactive Compound Attenuates Polycystic Ovary Syndrome through Modulation of PPAR-γ/SREBP-1c Gene Expression: A Comparative Preclinical Study with Metformin

Abstract

Polycystic Ovary Syndrome (PCOS) affects 8-13% of reproductive- age women worldwide and is characterized by metabolic, hormonal, and oxidative stress disturbances. Current therapies such as metformin provide symptomatic relief but do not address the multifactorial pathophysiology. This study aimed to evaluate the therapeutic efficacy of amygdalin, a naturally occurring bioactive compound, compared with metformin, focusing on modulation of PPAR-γ and SREBP-1c gene expression in a murine PCOS model. PCOS was induced in female mice using a high-fat diet plus letrozole. Amygdalin (150 and 300 mg/kg) or metformin (200 mg/kg) was administered orally for 21 days. Ovarian tissue was evaluated for biochemical, hormonal, oxidative stress, inflammatory, and molecular parameters, including gene expression of PPAR-γ and SREBP-1c. Amygdalin treatment enhanced insulin resistance and hyperglycemia similar to metformin. Metformin had slightly better lipid-modulating activity (reduction of TC and TG), whereas amygdalin had a remarkable antioxidant capacity (+15 % GSH). Both therapies reduced inflammatory markers and normalised estrogen levels. Amygdalin resulted in greater upregulation of PPAR-γ mRNA (2.1-fold vs 1.8-fold with metformin) and more efficient suppression of SREBP-1c mRNA expression, suggesting differences in the transcriptional regulation of lipid metabolic pathways between amygdalin and metformin. Amygdalin demonstrated multitarget activity, including metabolic modulation, hormonal balance, and antioxidant defense, comparable to metformin but with stronger antioxidant effects. Its regulation of PPAR-γ/SREBP-1c and anti-inflammatory properties highlight its potential in oxidative stress-driven PCOS phenotypes. Amygdalin is a promising natural therapeutic candidate for PCOS via metabolic, hormonal and antioxidant pathways. The compound’s ability to modulate PPAR-γ/SREBP-1c gene expression suggests its translational potential as an adjunct or alternative to conventional therapies.