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      Therapeutic Effects of Pimpinella anisum Fruit Extract on Polycystic Ovary Syndrome in a Rat Model: Emerging Role of Inflammatory Responses and Oxidative Stress

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          Abstract

          Background

          Polycystic ovary syndrome (PCOS) is the most common gynecological endocrine disorder.

          Objectives

          This study evaluated the therapeutic effects of Pimpinella anisum L. ( P. anisum) fruit on pro-inflammatory cytokines, oxidative stress markers, and ovarian tissue structure in a rat model of PCOS.

          Methods

          After inducing PCOS, female Wistar rats were randomly divided into control and PCOS groups. They orally received daily doses of normal saline or hydro-alcoholic extract of P. anisum at two doses (200 and 400 mg/kg) for 21 days. At the end of the treatment period, ovarian and liver tissues were collected to measure lipid peroxidation, antioxidant status, TNF-α, IL-6 mRNA expression, and its content. Additionally, histopathological examinations of the ovarian tissue were conducted.

          Results

          Our findings revealed a dose-dependent change in the biochemical and histopathological parameters. Treatment with P. anisum resulted in a significant decrease in TNF-α and IL-6 mRNA expression levels and their content in the ovarian and liver tissues. It also reduced MDA levels while increasing SOD and GPx activity in both ovarian and liver tissues of PCOS rats. Furthermore, the number of follicular cysts in the PCOS rat model was significantly reduced.

          Conclusions

          The beneficial effects of P. anisum in PCOS rats are partly attributed to the inhibition of inflammatory and oxidative stress markers in ovarian tissue. These findings suggest that P. anisum could be a potential candidate for the treatment of PCOS disorders

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          Most cited references58

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          The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria.

          Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder in women of reproductive age, yet debate over appropriate diagnostic criteria and design limitations with sampling methodology have left some doubt as to the actual prevalence in the community. The objective of this study was to create a representative prevalence estimate of PCOS in the community under the National Institutes of Health (NIH) criteria and the more recent Rotterdam consensus criteria and Androgen Excess Society (AES) criteria. A retrospective birth cohort study was carried out in which 728 women born during 1973-1975 in a single maternity hospital were traced and interviewed in adulthood (age = 27-34 year; n = 728). Symptoms of PCOS (hyperandrogenism, menstrual dysfunction and polycystic ovaries) were identified by examination and the presence of polycystic ovaries in those that did not consent to the ultrasound were imputed. The estimated prevalence of PCOS in this birth cohort using the NIH criteria was 8.7 +/- 2.0% (with no need for imputation). Under the Rotterdam criteria, the prevalence was 11.9 +/- 2.4% which increased to 17.8 +/- 2.8% when imputed data were included. Under the AES recommendations, PCOS prevalence was 10.2 +/- 2.2%, and 12.0 +/- 2.4% with the imputed data. Of the women with PCOS, 68-69% did not have a pre-existing diagnosis. The Rotterdam and AES prevalence estimates were up to twice that obtained with the NIH criteria in this, as well other prevalence studies. In addition, this study also draws attention to the issue of many women with PCOS in the community remaining undiagnosed.
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            The effects of oxidative stress on female reproduction: a review

            Oxidative stress (OS), a state characterized by an imbalance between pro-oxidant molecules including reactive oxygen and nitrogen species, and antioxidant defenses, has been identified to play a key role in the pathogenesis of subfertility in both males and females. The adverse effects of OS on sperm quality and functions have been well documented. In females, on the other hand, the impact of OS on oocytes and reproductive functions remains unclear. This imbalance between pro-oxidants and antioxidants can lead to a number of reproductive diseases such as endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility. Pregnancy complications such as spontaneous abortion, recurrent pregnancy loss, and preeclampsia, can also develop in response to OS. Studies have shown that extremes of body weight and lifestyle factors such as cigarette smoking, alcohol use, and recreational drug use can promote excess free radical production, which could affect fertility. Exposures to environmental pollutants are of increasing concern, as they too have been found to trigger oxidative states, possibly contributing to female infertility. This article will review the currently available literature on the roles of reactive species and OS in both normal and abnormal reproductive physiological processes. Antioxidant supplementation may be effective in controlling the production of ROS and continues to be explored as a potential strategy to overcome reproductive disorders associated with infertility. However, investigations conducted to date have been through animal or in vitro studies, which have produced largely conflicting results. The impact of OS on assisted reproductive techniques (ART) will be addressed, in addition to the possible benefits of antioxidant supplementation of ART culture media to increase the likelihood for ART success. Future randomized controlled clinical trials on humans are necessary to elucidate the precise mechanisms through which OS affects female reproductive abilities, and will facilitate further explorations of the possible benefits of antioxidants to treat infertility.
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              Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome.

              Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
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                Author and article information

                Contributors
                Journal
                Iran J Pharm Res
                Iran J Pharm Res
                10.5812/ijpr
                Brieflands
                Iranian Journal of Pharmaceutical Research : IJPR
                Brieflands
                1735-0328
                1726-6890
                09 March 2024
                Jan-Dec 2024
                : 23
                : 1
                : e143290
                Affiliations
                [1 ]Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
                [2 ]Student Research Committee, Health School, Ardabil University of Medical Sciences, Ardabil, Iran
                [3 ]Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
                [4 ]Department of Microbiology & Immunology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
                [5 ]Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
                [6 ]Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
                [7 ]Students Research Committee, Pharmacy School, Ardabil University of Medical Sciences, Ardabil, Iran
                Author notes
                [* ]Corresponding Author: Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. Email: dr.moeeni@ 123456yahoo.com
                Author information
                https://orcid.org/0000-0001-8649-8476
                https://orcid.org/0000-0003-0897-5972
                https://orcid.org/0000-0002-3836-3240
                https://orcid.org/0000-0002-2628-9864
                https://orcid.org/0000-0002-8950-9879
                https://orcid.org/0000-0002-9016-3086
                https://orcid.org/0000-0003-2431-1156
                https://orcid.org/0000-0001-9419-1490
                https://orcid.org/0000-0001-5004-1941
                Article
                10.5812/ijpr-143290
                11246645
                39005731
                979dc913-3e29-4f9d-8a02-7b30ff7fc34e
                Copyright © 2024, Dadkhah et al

                This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License ( https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.

                History
                : 22 November 2023
                : 20 January 2024
                : 13 February 2024
                Categories
                Research Article

                pimpinella anisum,polycystic ovary syndrome,oxidative stress,inflammation,rat

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