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      Polysaccharides of Fructus corni Improve Ovarian Function in Mice with Aging-Associated Perimenopause Symptoms

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          Abstract

          Objective

          Perimenopause symptoms have an extremely high incidence in aging women. Development of new strategies to improve perimenopause symptoms is important topic in clinical context. Increasing studies have shown that the polysaccharides of Fructus corni (PFC) have many pharmacological activities including antiaging effects. Here, we evaluated the effects of PFC on the ovarian function in natural aging-associated perimenopause symptoms in mice.

          Methods

          Natural aging mice (16-month old) were orally administrated with PFC at 1.11 g/kg daily for 24 days with none-treated young mice (3-month old) as control. Blood samples were collected for measurements of serum levels of estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH). Ovaries were isolated for histopathological and molecular exanimations.

          Results

          We found that the aging mice had decreased number of growing follicles and corpus luteum in ovary, but treatment with PFC restored their amounts. Measurement of hormones showed that there were low serum levels of estradiol and progesterone but high levels of LH and FSH in aging mice; however PFC restored estradiol and progesterone levels but reduced LH and FSH levels. Immunohistochemical analysis with ovarian tissues also revealed that the expression of inhibin and insulin-like growth factor 1 was reduced in the ovary of aging mice but was restored by PFC. These data indicated that PFC regulated ovarian function-associated hormone levels in aging mice. Furthermore, there was reduced expression of antiapoptotic protein Bcl-2 and increased expression of proapoptotic molecules Bax and cleaved-caspase-3 in the ovary of aging mice. However, treatment with PFC upregulated Bcl-2 and downregulated Bax and cleaved-caspase-3, suggesting that PFC inhibited apoptosis of granulosa cells in the ovary of aging mice.

          Conclusion

          PFC improved the ovarian function in mice, which had high potential to be developed as a safe and effective therapeutic remedy for aging-associated perimenopause symptoms.

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          Most cited references24

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          Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women.

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            Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity.

            The neuroprotective effects of estrogen have been demonstrated consistently in cellular and animal studies but the evidence in women remains conflicted. We explored the window of opportunity hypothesis in relation to cognitive aging and dementia. In particular, we reviewed existing literature, reanalyzed some of our data, and combined results graphically. Current evidence suggests that estrogen may have beneficial, neutral, or detrimental effects on the brain depending on age at the time of treatment, type of menopause (natural versus medically or surgically induced), or stage of menopause. The comparison of women who underwent bilateral oophorectomy with referent women provided evidence for a sizeable neuroprotective effect of estrogen before age 50 years. Several case-control studies and cohort studies also showed neuroprotective effects in women who received estrogen treatment (ET) in the early postmenopausal stage (most commonly at ages 50-60 years). The majority of women in those observational studies had undergone natural menopause and were treated for the relief of menopausal symptoms. However, recent clinical trials by the Women's Health Initiative showed that women who initiated ET alone or in combination with a progestin in the late postmenopausal stage (ages 65-79 years) experienced an increased risk of dementia and cognitive decline regardless of the type of menopause. The current conflicting data can be explained by the window of opportunity hypothesis suggesting that the neuroprotective effects of estrogen depend on age at the time of administration, type of menopause, and stage of menopause. Therefore, women who underwent bilateral oophorectomy before the onset of menopause or women who experienced premature or early natural menopause should be considered for hormonal treatment until approximately age 51 years. Copyright © 2010 Elsevier B.V. All rights reserved.
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              The aging ovary--the poor granulosa cells.

              The development of a competent oocyte intimately depends on the maintenance of energetic homeostasis in the ovarian and follicular microenvironment. On this basis, it is very likely that the oocyte ages as the ovary ages. Starting from the molecular evidence for energy perturbations in the whole ovary, we review current knowledge on the involvement of endogenous highly reactive metabolites in follicle aging. The first part provides an update of recent findings that confirm the key role of oxidative stress in aged granulosa cells. The second part focuses on studies providing evidence for the implication of advanced glycation end product (AGE) in aging reproductive dysfunction. With their prolonged half-life and ability to act as signaling molecules AGEs may gradually accumulate in the ovary and potentiate the wide spatiotemporal spread of oxidative stress. Clinical evidence for this view supports the hypothesis that AGE is a good candidate as a predictive marker and therapeutic target in new strategies for improving reproductive counseling in aging women.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2019
                27 June 2019
                27 June 2019
                : 2019
                : 2089586
                Affiliations
                1Department of Pharmacy, Jiangsu Jianhu People's Hospital, Yancheng 224700, China
                2School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing 210023, China
                3Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
                Author notes

                Guest Editor: Glaura Fernandes

                Author information
                https://orcid.org/0000-0002-3492-6325
                https://orcid.org/0000-0002-2924-2287
                Article
                10.1155/2019/2089586
                6620845
                70d207d9-9380-4643-b5c6-b31fc7fc7d68
                Copyright © 2019 Yong Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 March 2019
                : 14 May 2019
                : 26 May 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 30772851
                Funded by: Nanjing University of Chinese Medicine
                Award ID: 08JCQN10
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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