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Abstract Background Polycystic ovarian syndrome (PCOS) is a reproductive disorder associated with several endocrine and metabolic alterations. The mechanism underlying this syndrome is controversial. On the other hand, drugs used for the treatment are associated with several side effects and poor in controlling PCOS phenotype. l-Carnitine (LC) has been reported to have a significant regulatory function on the redox and metabolic status of female reproductive system. Nevertheless, its regulatory pathways to regulate PCOS are still under investigation. Therefore, this study aimed to evaluate the effects of LC on the steroidogenic pathways, oxidative stress markers and metabolic profile in letrozole (LTZ)-induced PCOS rat model. Methods For this aim, animals were divided into four groups (n = 6). Control group, untreated letrozole-induced PCOS group (1 mg/kg bwt) for 21 days, PCOS group treated with l-Carnitine (100 mg/kg bwt) for 14 days and PCOS group treated with clomiphene citrate (2 mg/kg bwt) for 14 days. Finally, body and ovarian weight, metabolic state(glucose and lipid profile), hormonal assays (testosterone, 17 β estradiol, LH and FSH levels), intraovarian relative gene expression (CYP17A1, StAR, CYP11A1 and CYP19A1 genes), ovarian redox state (malondialdehyde (MDA), reduced glutathione content (GSH) and catalase enzyme activity (CAT)) as well as serum total antioxidant capacity (TAC) were detected. Also, histomorphometric ovarian evaluation (number and diameter of cystic follicles, granulosa cell thickness and theca cell thickness) as well as immune expression of caspase-3 of granulosa cells of cystic follicles were determined. Results LC significantly improved ovarian redox state (GSH, MDA and CAT), steroidogenic pathways gene expression (CYP17A1, StAR, CYP11A1 and CYP19A1 genes), hormonal profile (Follicle stimulating hormone (FSH) and luteinizing hormone (LH), testosterone and estradiol), metabolic state (Glucose and lipid profile) histomorphometric alterations and decreased caspase 3 immune reaction of granulosa cells. Conclusion l-Carnitine supplementation can ameliorate the PCOS phenotype through its energetic, antioxidant and antiapoptotic functions as well as steroidogenesis regulatory role. This protocol could be modified to produce the best therapeutic benefits, and it could be regarded as a prospective therapeutic intervention for PCOS.

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk. [ABSTRACT FROM AUTHOR]

Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS). In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model. Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured. In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS. In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations. [Display omitted] • UPLC-MS2 analysis procured the detection of 35 metabolites in CSE (Cicer arietinum seeds extract). • Formononetin and biochanin A were the major identified isoflavones in CSE. • CSE amended lipid profile, oxidative stress and blood glucose and in letrozole induced PCOS in rats. • CSE improved sex hormones, restored estrus cyclicity and prevented ovarian damage. • CSE increased Ki-67 in granulosa cells and downregulated Cyp11a1 mRNA expression in ovarian tissue. [ABSTRACT FROM AUTHOR]