Comparison of the therapeutic effect of berberine with metformin in rats with polycystic ovary syndrome induced by letrozole

Background and Aim: Polycystic ovary syndrome (PCOS) causes infertility, ovulatory dysfunction, insulin resistance, irregular menstruation, obesity, hyperandrogenism and dyslipidemia. This study aims to create a letrozole-mediated PCOS model in rats and to evaluate the effects of berberine, which has similar mechanisms to metformin that is currently used in the treatment of PCOS, and to compare them with each other based on vaginal smear, serum hormone levels (testosterone, estradiol, leptin), ovarian histopathology and immunohistochemical findings. Material and Methods: Thirty two Wistar albino adult female rats, produced under standard laboratory conditions and with the same physiological and biological characteristics, were used in this study. The rats divided into four groups: 1.Control group (n=8), 2.PCOS group (n=8), 3.PCOS + Metformin group (n=8) and 4.PCOS + Berberine group (n=8). In order to create a PCOS model, 1 mg/kg letrozole dissolved in dimethyl sulfoxide (DMSO) was administered intragastric (i.g.) to the subjects of the 2nd, 3rd and 4th groups, once a day for 21 consecutive days. Then, for treatment purposes, subjects in the 3rd group were given 300 mg/kg/day metformin dissolved in distilled water for 2 weeks, and subjects in the 4th group were given 200 mg/kg/day berberine dissolved in distilled water i.g. for 2 weeks was given by i.g. Fasting blood sugar was measured with a glucometer in blood taken from the tail vein before sacrification. ELISA method was used for testosterone, estradiol and leptin levels in serum. To determine estrous cycle phases, vaginal smear samples were stained with Hematoxylin + Eosin (H+E). Paraffin inclusion was applied to ovaries taken from all animals. To show the general histological features of the ovary, sections were stained with H+E and Masson Trichrome. Ovarian follicles at various developmental stages, corpus luteums, atretic follicles and cystic follicles resulting from PCOS were examined under the light microscopy. AMPK, SIRT-1, PCNA and NRF-2 immunoreactivities were also evaluated by histological scoring method. Results: Significant increases in body weight, fasting blood sugar, cystic follicle and atretic follicle numbers, serum testosterone and leptin levels were determined in the PCOS group compared to the control group (all p<0.05). All subjects in this group represented irregular estrous cycles. Additionally, PCOS caused a significant decrease in corpus luteum count, serum estradiol level, AMPK, SIRT-1, PCNA and NRF-2 immunoreactivities (all p<0.05). It was determined that the two treatment methods, metformin and berberine, showed similar effects to each other and significantly brought all changes closer to normal. Conclusion: Our findings show that berberine can eliminate PCOS-induced changes in both the ovarian structure, hormones and estrous cycle, by acting equivalent to metformin, which is currently used in the treatment of PCOS. Considering the side effects that metformin causes in people during the treatment process, we believe that berberine, can be a high-potential alternative for the PCOS treatment.