Phytochemical-rich extract of Psidium guajava ameliorates letrozole-induced PCOS in female rats by modulating the NF-κB inflammatory pathway.

Polycystic ovarian syndrome is a multidisciplinary endocrinopathy with complex symptomatology. This study aimed to explore the pharmacological potential of the ethanolic extract of Psidium guajava (EEPG) in PCOS with a mechanistic approach and its effects on ovarian histopathology. EEPG was characterized by using HPLC. Thirty female adult rats were divided into six groups (n = 5): the normal control, the disease-induced, metformin, and EEPG (200, 400, and 600 mg/kg). PCOS was induced by administering letrozole (1 mg/kg). Biochemical, molecular, and histopathological evaluations were performed. HPLC analysis revealed the presence of various phytoconstituents in the ethanolic extract of Psidium guajava, such as chlorogenic acid, gallic acid, HB acid, caffeic acid, vanillic acid, kaempferol, sinapic acid, ferulic acid, salicylic acid, coumarin, quercetin, benzoic acid, rutin, and coumaric acid. The study findings revealed that letrozole significantly elevated weight, insulin, LH, LH/FSH ratio, and testosterone levels, and decreased FSH and estrogen levels. Ovarian histopathology showed a diseased pattern with a thick granulosa cell compartment, more prominent cystic follicles, and a lesser amount of primary, secondary, and Graafian follicles. Treatment with EEPG resulted in weight reduction, normalization of the hormonal profile, and restoration of ovarian histopathology in a dose-dependent manner. EEPG ameliorated metabolic and reproductive dysfunction in PCOS by reducing oxidative stress and suppressing NF-κB-mediated inflammatory responses, thereby improving ovarian function.