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.

Chitosan/Alginate-loaded Astragalus hamosus shows ameliorating effects on lipid profile, inflammatory and hormonal parameters, and reduces miRNA-222 expression in Polycystic Ovary Syndrome Rats

“…The epithelium thickness decreased and the number of normal endometrial glands increased after treatment. These ndings agree with the results of previous studies, in which various treatments including Silibinin [42], Melatonin and Metformin [44], Vitamin D [45], Metformin [41], dodder total avone [46], and Ageratum conyzoides [36] were used.…”

“…The presence of endometrial hyperplasia in the uteri is considered a histological indicator of PCOS [40]. Our results indicated that abnormal alteration of uterine morphology including hyperplasia, decreased number of endometrial glands, the appearance of cystic glands, and thickening of the lining epithelium were obvious in the PCOS group consistent with previous studies [41,42]. In this study, two types of endometrial glands were detected in the uterine sections according to Gunin et al [43] including normal and cystic glands.…”

Suppression of neurotransmission on gonadotropin-releasing hormone neurons in letrozole-induced polycystic ovary syndrome: A mouse model

“…In addition, letrozole-fed mice demonstrated reduced pregnancy outcomes even though a copulatory plug was detected in females from both groups of breeding pairs. Previous findings show impaired fertility in the letrozole-induced PCOS models ( 10 ), as well as abnormalities in the ovarian and uterine tissues ( 15 , 37 ) and the development of cystic ovary ( 15 , 38 ). These reported findings could support the possibility of impaired fertility even though a copulatory plug was detected in our letrozole-fed mice.…”

Evidence for causal effects of polycystic ovary syndrome on oxidative stress: a two-sample mendelian randomisation study

“…A few antioxidants can ameliorate PCOS through reducing OS, such as Tempol [ 36 ], Kelulut honey [ 37 ], Standardised Aronia melanocarpa [ 38 ], astaxanthin [ 39 ], resveratrol [ 40 ], and N-acetyl cysteine [ 41 ]. Besides, silibinin [ 42 ] and vitamin E supplementation [ 43 ] as well as melatonin and/or magnesium supplementation [ 44 ] also ameliorate PCOS by reducing the level of OS.…”