Protective Potential of Methanol Extract of Drymaria cordata Willd. ex Schult (MEDC) on Letrozole-Induced Polycystic Ovary Syndrome Via Modulation of Apoptotic Markers, Sex Hormones and Antioxidant Status in Rat Model

Abstract

Polycystic ovary syndrome (PCOS) is a gynecological disorder among reproductive-aged women and a major cause of infertility. Different treatment options are being employed but with side effects. This has mandated alternative treatment options, especially complementary therapy. This study therefore investigated the possible protective effects of methanol extract of Drymaria cordata in Letrozole-induced PCOS. The plant is folklorically used in the treatment of diverse ailments including PCOS, fibroids, uterine/ovarian/breast tumors, and cancers. Forty-eight female Wistar rats were acclimatized and initially divided into two groups: group I(control group) and group II(PCOS group). PCOS was induced by the oral administration of letrozole/high-fat diet for 21 days. After the induction, the PCOS group was sub-divided into four groups (n = 4): group II (positive control with PCOS), group III (MET 2mg/kg), group IV (MEDC 200mg/kg), and group V (MEDC 400mg/kg). Rats were orally treated with MET and MEDC for six weeks after the PCOS induction. At the end of the experimental period, blood samples were collected, sera were separated, mitochondria were isolated, and the mPT, some apoptotic biomarkers, hormonal and lipid profiles, and oxidative stress markers were determined. Ovarian histological evaluation and GC-MS analysis of MEDC were carried out. There was no significant mPT pore opening in the PCOS (untreated) group. However, treatments with MEDC caused significant mPT pore opening, upraised caspase 9, caspase 3, and Bax, and decreased anti-apoptotic Bcl-2 levels. The MEDC treatments restored the hormonal and lipid profiles, increased the levels of GSH-Px and SOD and decreased TBARS. Histological examination revealed resolved ovarian cysts and improved follicular growth with MEDC treatments. Comparable results were observed for both MEDC and metformin. The GC-MS analysis revealed the presence of some major pharmacologically relevant compounds. These findings suggest that MEDC contains phytochemicals that can protect against letrozole-induced PCOS possibly by normalizing the impaired hormonal balance, restoring the lipid profile, and improving the antioxidant milieu of the system.

Keywords: Drymaria cordata; Hyperandrogenism; Letrozole; Mitochondrial permeability transition pore; Oxidative stress; Polycystic ovary syndrome.