Exploring the Antioxidative Effects of Ginger and Cinnamon: A Comprehensive Review of Evidence and Molecular Mechanisms Involved in Polycystic Ovary Syndrome (PCOS) and Other Oxidative Stress-Related Disorders.

Oxidative stress represents the pathophysiological basis for most disorders, including reproductive issues. Polycystic ovary syndrome (PCOS) is heterogeneous endocrine disorder of women characterized primarily by irregular menstrual cycles, hyper-androgenism, and ovulatory dysfunction. In the last decades, PCOS was recognized as a systemic silent inflammation and an oxidative disturbance-related disorder, exerting multifaceted symptoms, including metabolic. PCOS treatment should involve a personalized approach tailored to individual symptoms; however, the results are often unsatisfactory. Various supplementary treatments have been proposed to assist in the management and alleviation of PCOS symptoms. Cinnamon and ginger, known for millennia as herbs used in spices or traditional medicine for the treatment of various diseases, are of interest in this study. The aim of this study is to evaluate and investigate the effects of cinnamon and ginger in PCOS patients. Using relevant keywords we searched through PubMed/MEDLINE, Science Direct, Google Scholar and Web of science to find animal studies, pre-clinical, and clinical studies which were then reviewed for usage. Out of all of the reviewed studies a total of 65 studies were included in this review article. Cinnamon and ginger can affect hormonal status, lipid profile, obesity, and insulin resistance by mitigating oxidative stress and inflammation. Generally, based on current clinical evidence, it was revealed that supplementation with cinnamon or ginger had a useful impact in patients with PCOS. This review summarizes the antioxidative effects of ginger and cinnamon in PCOS treatment, highlighting their potential benefits in other oxidative stress-related pathologies.

High Fat Diet Exaggerate Metabolic and Reproductive PCOS Features by Promoting Oxidative Stress: An Improved EV Model in Rats.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.

The Potential of SGLT-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: The Current Status and Future Perspectives.

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy during women's reproductive age. PCOS is a heterogeneous disorder featuring specific cardiometabolic properties. The association between the presence of metabolic disorders and PCOS supports the claim that the regulation of glycemic status is very important in these patients. There is a wide range of therapeutic options (including those treating diabetes mellitus type 2) with potential advantages available for the management of PCOS. Sodium-glucose cotransporter type 2 inhibitors (SGLT-2is) improve glucose metabolism, reduce fat tissue, lower blood pressure, reduce oxidative stress and inflammation, and protect the cardiovascular system. Currently, the use of SGLT-2is is not widespread in PCOS therapy, although these drugs represent a promising new therapeutic approach. Therefore, it is necessary to initiate further study in order to determine more effective therapies for PCOS and investigate the effect of SGLT-2is, both as a monotherapy and in combination with other drugs. It is necessary to understand the mechanisms underlying SGLT-2is in PCOS and their effects on long-term complications, especially since the gold standard treatment for PCOS, such as metformin and oral contraceptives, do not have long-term cardioprotective effects. The effects of SGLT-2is seem to involve cardiac protection, while diminishing endocrine and reproductive abnormalities in PCOS. In the current narrative review, we examine the most recent clinical evidence and discuss the potential applications of SGLT-2is for PCOS therapy.

The Expression of IL-1ß Correlates with the Expression of Galectin-3 in the Tissue at the Maternal-Fetal Interface during the Term and Preterm Labor.

The inflammatory processes that occur at the maternal−fetal interface are considered one of the factors that are responsible for preterm birth. The pro-inflammatory roles of the Gal-3-induced activation of NLRP3 inflammasome and the consecutive production of IL-1ß have been described in several acute and chronic inflammatory diseases, but the role of this inflammatory axis in parturition has not been studied. The aim of this study was to analyze the protein expression of Gal-3, NLRP3, and IL-1ß in the decidua, villi, and fetal membranes, and to analyze their mutual correlation and correlation with the clinical parameters of inflammation in preterm birth (PTB) and term birth (TB). The study included 40 women that underwent a preterm birth (gestational age of 25.0−36.6) and histological chorioamnionitis (PTB) and control subjects, 22 women that underwent a term birth (gestational age of 37.0−41.6) without histological chorioamnionitis (TB). An analysis of the tissue sections that were stained with anti- Gal-3, -NLRP3, and -IL-1ß antibodies was assessed by three independent investigators. The expression levels of Gal-3 and IL-1ß were significantly higher (p < 0.001) in the decidua, villi, and fetal membranes in the PTB group when they compared to those of the TB group, while there was no difference in the expression of NLRP3. A further analysis revealed that there was no correlation between the protein expression of NLRP3 and the expression of Gal-3 and IL-1ß, but there was a correlation between the expression of Gal-3 and IL-1ß in decidua (R = 0.401; p = 0.008), villi (R = 0.301; p = 0.042) and the fetal membranes (R = 0.428; p = 0.002) in both of the groups, PTB and TB. In addition, the expression of Gal-3 and IL-1ß in decidua and the fetal membranes was in correlation with the parameters of inflammation in the maternal and fetal blood (C-reactive protein, leukocyte number, and fibrinogen). The strong correlation between the expression of Gal-3 and IL-1ß in the placental and fetal tissues during labor indicates that Gal-3 may participate in the regulation of the inflammatory processes in the placenta, leading to increased production of IL-1ß, a cytokine that plays the main role in both term and preterm birth.

Antioxidative Effects of Standardized Aronia melanocarpa Extract on Reproductive and Metabolic Disturbances in a Rat Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) represents the most common endocrinopathy among childbearing-age women, with oxidative stress (OS) underlying its etiopathogenesis. Metformin (MET) represents a frequently used agent in PCOS. However, weak results encourage alternative treatments. We aimed to investigate isolated and synergistic effects of Standardized Aronia melanocarpa extract (SEA) and MET for alleviating reproductive and metabolic PCOS abnormalities. PCOS induction was followed by 28-day treatment with MET, SAE, or MET + SEA. Bodyweight (BW), cyclicity, histological, and ultrasonographical ovarian analyses were performed. Hormonal, glycemic, and lipid profiles were accessed, as well as systemic and ovarian oxidative status; BW, cyclicity, ovarian histomorphology, ovarian volume, testosterone and progesterone levels, as well as LDL, triglycerides, and total cholesterol levels were aggravated after PCOS-induction and improved after MET, SEA, and MET + SEA treatment. MET + SEA had the greatest impact on glycoregulation. Alterations in OS parameters (TBARS, O2-, H2O2, catalase, superoxide dismutase, and reduced glutathione) could be responsible for observed differences; (4) Conclusions: Our findings confirmed that SAE alone or along with MET was capable of ameliorating reproductive and metabolic disturbances in the PCOS rat model, with the restoration of OS parameters. SAE alone did not alter the protective effects of MET in PCOS.

Normotensive rats with PCOS exhibit the hypertensive pattern: focus on oxidative stress.

Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. In this study, we aimed to investigate the potential strain differences in ovarian morphology, hemodynamic, and biochemical characteristics in an androgen-induced PCOS rat model. A total of 24 rats of 3 weeks old (12 Wistar Kyoto - WK and 12 spontaneously hypertensive rats - SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily s.c. injections of testosterone enanthate (1 mg/100 g body weight) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic, and cystic follicles). Ultrasonographically, a significant decrease in ovarian volume (OV) was registered in PCOS groups but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial, and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, thiobarbituric acid reactive substance and superoxide anion radical levels were higher in both strains, while superoxide dismutase and glutathione were significantly lowered.

Cardiovascular Properties of the Androgen-Induced PCOS Model in Rats: The Role of Oxidative Stress.

Polycystic ovary syndrome (PCOS) is a multifaced reproductive endocrinopathy affecting 6-20% of women of childbearing age. It was previously shown that women with PCOS have an increased risk of cardiovascular (CV) diseases. The aim of this study was to evaluate the cardiodynamic parameters of isolated rats' hearts, blood pressure levels, and histomorphological changes in the heart tissue following the androgen-induced PCOS model in rats and the role of oxidative stress in the development of these CV properties of PCOS. 21-day-old female rats (n = 12) were divided into control and PCOS groups. PCOS was induced by administration of testosterone enanthate (1 mg/kg BW, daily) during 35 days. During the autoregulation protocol (40-120 mmHg) on the Langendorff apparatus, ex vivo cardiodynamic parameters of retrogradely perfused hearts showed enhanced contractile function and increased lusitropic effects in the left ventricle (LV) in PCOS rats. Systolic and diastolic pressures in LV were elevated at all perfusion pressure values. Systemic arterial systolic blood pressure showed borderline elevation, while mean arterial blood pressure was significantly higher in PCOS rats. Histological evaluation of heart tissue depicted hypertrophic (8.3%) alterations in LV cardiomyocytes and increase (7.3%) in LV wall thickness. Oxidative stress parameters were altered in systemic circulation, coronary venous effluent (CVE), and heart tissue. Levels of superoxide dismutase and reduced glutathione were decreased in blood and heart tissue, while catalase activity was not altered. Degree of lipid peroxidation was increased in circulation as well as heart tissue. Increased levels of O2 - in CVE indicated the cardiotoxic effects in the rat PCOS model. The mentioned alterations of oxidative stress parameters in the blood, CVE, and heart could be recommended as potential contributors underlying the development of CV risk in PCOS women.