Therapeutic Effects of Silibinin Against Polycystic Ovary Syndrome Induced by Letrozole in Rats via Its Potential Anti-Inflammatory and Anti-Oxidant Activities

Abstract

Background: Current therapies for polycystic ovary syndrome (PCOS) are accompanied by unwanted effects. Silibinin; a flavonolignan has pleiotropic activities and favorable safety profile. Purpose: To investigate the efficacy of silibinin on estrous cyclicity, inflammation, oxidative stress and ovarian morphology in letrozole-induced PCOS in rats. Methods: Forty-eight female Wistar albino rats were divided into 2 sets. Rats of the first set (n = 12), assigned as a negative control (NC) received only the vehicle, rats of the second set (n = 36), assigned as PCOS rats, were given letrozole 1mg/Kg orally for 21 days. On day 21, six rats from the first set and six rats from the second set were euthanized for confirmation of PCOS-induction. The remaining animals from the first set assigned as group 1, those in the second set (n = 30) were equally divided into 5 groups and treated daily for 19 days as follows: group 2 (positive control) received only the vehicle, group 3 treated with metformin 300mg/Kg orally, groups 4 and 5 treated respectively with 100 and 200 mg/Kg silibinin intraperitoneally (IP), and group 6 treated with a combination of metformin 300mg/Kg orally and silibinin 100mg/Kg IP. On day 40, blood samples were examined for luteinizing hormone (LH), testosterone (TS) and estradiol (EST) levels, the anti-inflammatory and antioxidant parameters, ovarian and uterine morphology. Results: Silibinin alone or in combination with metformin was found to be effective in restoring the regularity of estrous cycle by ameliorating the abnormal alterations of LH, TS, EST, tumor necrosis factor (TNF)-α, and oxidative status and by resuming the appearance of corpora lutea and decreasing or even total absence of cystic follicles in the ovaries. Conclusion: Silibinin was effective in restoring estrous regularities and alleviating hormonal and histomorphological abnormalities of the ovarian and uterine tissues, this could be due to its anti-androgenic, anti-inflammatory and antioxidant properties.