Anti-androgenic compound Embelin ameliorates polycystic ovary syndrome by reversing the ovarian dysfunction and...

We could successfully reverse the polycystic ovary syndrome (PCOS) in a rat model using an anti-androgenic compound extracted from Embelia tsjeriam-cottam, which exhibited spectral characteristics consistent with Embelin. The identity of the anti-androgenic fraction was confirmed as Embelin using FT-IR, UV spectrophotometry, and UPLC-MS/MS analyses. The anti-androgenic activity of the extracted Embelin was evaluated using the Yeast RIKILT Androgen Assay and compared against (i) 5α-dihydrotestosterone (5α-DHT), (ii) a commercially sourced Embelin standard, and (iii) flutamide, a known androgen receptor antagonist. In silico molecular docking studies further revealed that Embelin exerts its anti-androgenic effects by competitively binding to the ligand-binding domain of the androgen receptor (AR), with interaction energy values comparable to those of 5α-DHT and hydroxyflutamide. The embelin fraction (up to 100 μl) and in combination with 5α-DHT, was non-toxic and promoted normal cell proliferation in vitro. Further, the extract also efficiently scavenged the 5α-DHT-induced Reactive Oxygen Species generation and downregulated the 5α-DHT-induced androgen receptor (AR) expression significantly in the in vitro system. A PCOS rat model was successfully established through 5α-DHT induction. Embelin treatment effectively reversed several hallmark features of PCOS, including ovarian dysfunction (e.g., hypo-progesteronemia, follicular cysts, and estrous cycle irregularities) as well as metabolic disturbances such as insulin resistance, weight gain, dyslipidaemia, and adipocyte hypertrophy. In conclusion, this is the first study to demonstrate the therapeutic potential of Embelin in ameliorating PCOS-related ovarian and metabolic dysfunctions.