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      Quercetin increases the antioxidant capacity of the ovary in menopausal rats and in ovarian granulosa cell culture in vitro

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          Abstract

          Background

          Menopause is the most important sign of aging in women, and the ovary is the organ most sensitive to aging. Quercetin is a potential antioxidant and free radical scavenger that is widely found in fruits, vegetables, and leaves. However, the effect of quercetin on ovarian aging has not been elucidated, and the mechanism underlying its antioxidative effect remains unclear. The purpose of the current study was to investigate whether quercetin protects ovarian function by decreasing oxidative stress.

          Methods

          In an in vivo experiment, female menopausal rats (12 months old) were intragastrically administered quercetin at three doses (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) for 90 days, and the estrous cycles were determined by vaginal smearing. In an in vitro experiment, rat primary ovarian granulosa cells were cultured and treated with H 2O 2 (400 μM) alone or H 2O 2 plus quercetin at 5 μM, 20 μM, or 50 μM. The levels of the hormones estradiol (E 2), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by radioimmunoassay. The serum levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione S-transferase (GST) were examined. The expression levels of the oxidative stress-related genes SOD-1, catalase (CAT) and glutathione synthetase (GSS) in the ovaries and ovarian granulosa cells were detected by Western blot.

          Results

          The in vivo results demonstrated that quercetin had no effects on ovarian morphology, hormone secretion, or the estrous cycle in menopausal rats. Although no significant changes were detected in the serum levels of T-AOC, SOD, GSH, GSH-PX, and GST between the quercetin and control groups, the mRNA and protein expression levels of the oxidative stress-related genes SOD-1, CAT and GSS in menopausal rat ovaries were increased by low-dose quercetin. Moreover, the in vitro results demonstrated that quercetin significantly rescued the decrease in cell viability by H 2О 2-induced oxidative stress and enhanced the H 2O 2-induced decrease in expression of oxidative stress-related proteins.

          Conclusions

          Together, the results of this study indicated that quercetin increased the antioxidant capacity of the ovary by upregulating the expression of some oxidative stress-related genes both in vivo and in vitro.

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          Most cited references23

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          Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models.

          Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic humanized models of cardiovascular disease. After evaluating its anti-oxidative and anti-inflammatory effects in cultured human cells, quercetin (0.1%, w/w in diet) was given to human CRP transgenic mice, a humanized inflammation model, and ApoE*3Leiden transgenic mice, a humanized atherosclerosis model. Sodium salicylate was used as an anti-inflammatory reference. In cultured human endothelial cells, quercetin protected against H(2)O(2)-induced lipid peroxidation and reduced the cytokine-induced cell-surface expression of VCAM-1 and E-selectin. Quercetin also reduced the transcriptional activity of NFκB in human hepatocytes. In human CRP transgenic mice (quercetin plasma concentration: 12.9 ± 1.3 μM), quercetin quenched IL1β-induced CRP expression, as did sodium salicylate. In ApoE*3Leiden mice, quercetin (plasma concentration: 19.3 ± 8.3 μM) significantly attenuated atherosclerosis by 40% (sodium salicylate by 86%). Quercetin did not affect atherogenic plasma lipids or lipoproteins but it significantly lowered the circulating inflammatory risk factors SAA and fibrinogen. Combined histological and microarray analysis of aortas revealed that quercetin affected vascular cell proliferation thereby reducing atherosclerotic lesion growth. Quercetin also reduced the gene expression of specific factors implicated in local vascular inflammation including IL-1R, Ccl8, IKK, and STAT3. Quercetin reduces the expression of human CRP and cardiovascular risk factors (SAA, fibrinogen) in mice in vivo. These systemic effects together with local anti-proliferative and anti-inflammatory effects in the aorta may contribute to the attenuation of atherosclerosis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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            Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice

            Increasing evidence shows that melatonin protected against age-related mitochondrial oxidative damage. However, the protective effects of melatonin against ovarian aging has not been explored. Young Kunming females (aged 2–3 months) were fed with melatonin added to drinking water for 6 or 12 months (mo). We found that long-term (12 mo) melatonin treatment significantly reduced ovarian aging, as indicated by substantial increases in litter size, pool of follicles, and telomere length as well as oocyte quantity and quality. Melatonin treatment suppressed ovarian mitochondrial oxidative damage by decreasing mitochondrial reactive oxygen species (mROS) generation, inhibiting apoptosis, repressing collapse of mitochondrial membrane potential and preserving respiratory chain complex activities. Female mice fed with melatonin had enhanced mitochondrial antioxidant activities, thus reducing the risk of mitochondrial oxidative damage cause by free radicals. Notably, melatonin treatment enhanced SIRT3 activity but not the protein expression level, and increased the binding affinity of FoxO3a to the promoters of both superoxide dismutase 2 (SOD2) and catalase (CAT). In conclusion, melatonin exerted protection against aging-induced fertility decline and maintenance of mitochondrial redox balance.
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              Antihypertensive effects of the flavonoid quercetin.

              The blood pressure lowering effect of a fruit and vegetable-rich diet is a necessary dietary lifestyle measure now included the guidelines for the management of arterial hypertension. Furthermore, flavonoids represent a major class of plant polyphenolics. The present review addresses the antihypertensive effect of quercetin, one of the most abundant flavonoids present in fruits and vegetables, and probably the best studied flavonoid because of its high biological activity. Quercetin has been shown to induce a progressive, dose-dependent and sustained reduction in blood pressure when given chronically in several rat models of hypertension, including spontaneously hypertensive rats, L-NAME-treated rats, DOCA-salt hypertensive rats, two-kidney one-clip Goldblatt rats, rats with aortic constriction and Dahl salt-sensitive hypertensive rats. Quercetin was also effective in reducing blood pressure in rat models of metabolic syndrome, including the obese Zucker rats as well as rats treated with a high-sucrose, high-fat diet. Quercetin also prevented morphological and functional changes in the heart, vessels and kidney, while increasing production of reactive oxygen species associated with hypertension. A high dose of quercetin also reduced blood pressure in stage 1 hypertensive patients in a randomized, double-blind, placebo-controlled, crossover study. Since raised blood pressure is the major cause of stroke as well as an important risk factor for ischemic heart disease, we propose that the blood pressure-lowering effect of quercetin could be an important mechanism contributing to the reduced risk of myocardial infarction and stroke observed with fruit and vegetables-rich diets, and possibly with flavonoid-rich diets.
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                Author and article information

                Contributors
                wangj_84321@163.com
                qianxiaoniude@163.com
                gaoqianghmu@qq.com
                angel200202003@163.com
                xujie@ems.hrbmu.edu.cn
                kinga@126.com
                dzhuhui@aliyun.com
                Journal
                J Ovarian Res
                J Ovarian Res
                Journal of Ovarian Research
                BioMed Central (London )
                1757-2215
                21 June 2018
                21 June 2018
                2018
                : 11
                : 51
                Affiliations
                ISNI 0000 0001 2204 9268, GRID grid.410736.7, Department of Physiology, College of Basic Medical Sciences, , Harbin Medical University, ; Harbin, China
                Author information
                http://orcid.org/0000-0001-8988-9245
                Article
                421
                10.1186/s13048-018-0421-0
                6013856
                29929541
                7f129a88-a37b-4dcb-b5d5-b87a9755d72a
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 December 2017
                : 23 May 2018
                Funding
                Funded by: Chinese National Natural Science Foundation
                Award ID: 81571957
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100008978, Health and Family Planning Commission of Heilongjiang Province;
                Award ID: 2016-168
                Award Recipient :
                Funded by: the Fundamental Research Funds for the Provincial Universitie
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Obstetrics & Gynecology
                ovary,menopause,oxidative stress,quercetin
                Obstetrics & Gynecology
                ovary, menopause, oxidative stress, quercetin

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