Management of metabolic and reproductive disturbances in letrozole induced polycystic ovarian syndrome by Asparagus racemosus roots

• In vivo PCOS model was developed following the Letrozole administration. • The root of Asparagus racemosus regulates the endocrinal dysregulation in PCOS by balancing gonadotropes, sex steroids and steroidogenic enzymes. • The ethanolic extract of above root attenuates hyperandrogenism induced intraovarian oxidative stress, inflammation and apoptosis. • It reduces excessive androgen receptor expression in the ovarian tissue of PCOS. • LC-ESI/MS profiling identified the bioactive phytotherapeutics in Asparagus racemosus. Polycystic Ovary Syndrome (PCOS) has emerged as a widespread endocrine health challenge for women in the childbearing phase by imposing an adverse influence on fertility. Unfortunately, the existing treatment-strategies are inadequate and largely focused on symptom-based relief. Therefore, the demand for safer herbal alternatives is more pressing than ever. Asparagus racemosus Willd. has a longstanding history as a traditional herb for addressing diverse hormonal and fertility complications. The present study explored the in-depth mechanism by which A. racemosus ethanolic extract (ARE) ameliorates letrozole-induced PCOS in female adult rats. ARE at different doses (100, 150, 250 mg/kg-bw) were concurrently supplemented in the letrozole-induced PCOS group (1 mg/kg-bw) for a continuous period of 21 days. LC/ESI-MS was employed for determination of active phytotherapeutics within the ARE. Biochemical assay, ELISA, native PAGE expression, Real-time PCR, immunostaining and histological study were implemented for the experimental analysis. ARE regularized the disrupted estrous pattern, improved metabolic status and balanced endocrine activity by reducing excess androgen production. ARE restored intraovarian antioxidant enzyme expression and markedly reduced the mRNA expression of inflammatory (NF-κB /TNF-α) and proapoptotic markers (Bax/P53) along with elevated expression of anti-apoptotic factor (BCL2). The downregulation of androgen receptor (AR) in ovarian tissue accompanied by a decreased in the angiogenic factor VEGF-B were also observed. ARE improved gonadal weights and histomorphology by limiting the formation of cystic follicles and promoting folliculogenesis. The presence of essential secondary metabolites, specifically steroidal sapogenin, isoflavones and polyphenols, is primarily responsible for these advantageous effects. The observed findings suggested that A. racemosus could be a highly effective safer alternative therapeutic intervention for managing the complexities of PCOS.