Patuletin Ameliorates Inflammation and Letrozole-Induced Polycystic Ovarian Syndrome in Rats

Concerns about inflammation-related issues affecting female reproductive health are growing. Chronic low-grade inflammation in women with polycystic ovarian syndrome (PCOS) affects follicular growth, ovulation, and androgen production. The present investigation aimed to elucidate the efficacy of flavonoid patuletin in ameliorating the letrozole-induced PCOS and associated inflammation in rats. Female Wistar rats (32 days old) were divided into five groups (n = 12): Group I, control; Group II, vehicle control; Group III, letrozole oral (1 mg/kg) for 28 days; Group IV and Group V treatment groups, patuletin i.p. (25 mg/kg) and clomiphene citrate + metformin i.p. (50 mg/kg + 300 mg/kg), respectively. Leterozole-induced PCOS and ovarian inflammation were ameliorated by patuletin, as reflected in the improved histopathology, prevention of cyst formation, significant upregulation of growth factors such as growth differentiation factor 9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) expression, and a decrease in the pro-inflammatory cytokines TNF-α, IL-6, and COX-2. Additionally, the plasma levels of reproductive hormones were restored. Upregulation of FSH-R, PR, and CYP19a1, along with downregulation of ERα, LHR, CYP17a1, CYP11a1 and HSDβ17a1, showed the regulation of gonadotropin receptors and steroid biosynthesis genes in ovarian tissues. Patuletin demonstrated a promising protective approach against the biological model of PCOS by increasing the inflammation in ovarian tissues with consequent regulation of growth factors, enzymes, and hormones, and might be used as adjuvant therapy in the treatment of problems related to female reproductive health.