Antioxidative and anti-inflammatory effects of monoterpene linalool in rats with letrozole-induced polycystic ovarian syndrome: modulation of autophagy and apoptosis.

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of reproductive age, frequently associated with infertility, metabolic complications, and chronic inflammation mediated by NF-κB activation. This is the first study to examine the effects of linalool (Lin), an acyclic monoterpene, on PCOS-related complications in rats. Adult female rats were randomly assigned to six experimental groups (n = 6): control, Lin 100, PCOS, PCOS + Lin 50, PCOS + Lin 100, and PCOS + Metformin (Met). To induce PCOS, letrozole (1 mg/kg) was administered orally to the rats for 21 days. After PCOS induction, the rats were orally treated with Lin (50 and 100 mg/kg) and Met (300 mg/kg) for 14 days. Linalool remarkably mitigated ovarian histopathological alterations and fibrosis and significantly improved fasting blood glucose levels and insulin sensitivity in PCOS rats. Hormonal disturbances in PCOS rats, including elevated LH and testosterone levels, decreased FSH levels, and increased LH/FSH ratio, were considerably ameliorated after Lin treatment. Additionally, Lin treatment markedly decreased oxidative stress and inflammatory responses in PCOS rats, as demonstrated by enhanced glutathione peroxidase activity and decreased malondialdehyde, NF-κB p65, and TNF-α levels. Linalool partially restored impaired autophagy in PCOS rats by upregulating LC3-I and LC3-II. Conversely, Lin administration significantly inhibited excessive ovarian apoptosis in PCOS rats through downregulating cleaved caspase-3 and reducing the cleaved caspase-3/procaspase-3 ratio. In summary, Lin improved PCOS-induced ovarian and metabolic abnormalities in rats by regulating oxidative stress, inflammation, autophagy, and apoptosis, highlighting its potential for PCOS management.