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      Pao Pereira Extract Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by inhibiting 5α-Reductase

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          Abstract

          Benign prostatic hyperplasia (BPH) is one of the most common diseases in the urinary system of elderly men. Pao extract is an herbal preparation of the bark of the Amazon rainforest tree Pao Pereira ( Geissospermum vellosii), which was reported to inhibit prostate cancer cell proliferation. Herein we investigated the therapeutic potential of Pao extract against BPH development in a testosterone-induced BPH rat model. The administration of testosterone induced the prostate enlargement, compared with the sham operated group with vehicle treatment. The BPH/Pao group showed reduced prostate weight comparable with BPH/finasteride group. Notably, Pao treatment did not significantly reduce body weights and sperm number of rats, compared with the control group. Furthermore, Pao extract treatment reduced the proliferative index in prostate glands and testosterone-induced expression levels of AR, as well as androgen-associated proteins such as SRD5A1 and PSA. Moreover, Pao extract and its active component, flavopereirine, induced cytotoxicity on human prostate epithelial RWPE-1 cells in a dose- and time- dependent manner with G2/M arrest. Consistently, Pao extract and flavopereirine suppressed the expression levels of SRD5A1, AR and PSA, respectively. Together, these data demonstrated that Pao extract suppresses testosterone-induced BPH development through inhibiting AR activity and expression, and suggested that Pao extract may be a promising and relative safe agent for BPH.

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          Most cited references48

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          Androgens and estrogens in benign prostatic hyperplasia: past, present and future.

          Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs. Published by Elsevier B.V.
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            Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients.

            5α-reductase inhibitors (5α-RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined. The goal of this review is to discuss 5α-RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects. We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride. Data reported in the literature were reviewed and discussed. Results.  Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship. We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia. © 2010 International Society for Sexual Medicine.
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              Inflammatory mediators in the development and progression of benign prostatic hyperplasia.

              Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men. Epidemiological data suggest a causal link between this condition and prostatic inflammation. The prostate is an immune-competent organ characterized by the presence of a complex immune system. Several stimuli, including infectious agents, urinary reflux, metabolic syndrome, the ageing process, and autoimmune response, have been described as triggers for the dysregulation of the prostatic immune system via different molecular pathways involving the development of inflammatory infiltrates. From a pathophysiological standpoint, subsequent tissue damage and chronic tissue healing could result in the development of BPH nodules.
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                Author and article information

                Contributors
                yunshifeng1@163.com
                rmhuang@simm.ac.cn
                yanjun@nju.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                23 December 2019
                23 December 2019
                2019
                : 9
                : 19703
                Affiliations
                [1 ]GRID grid.452564.4, State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, , Model Animal Research Center of Nanjing University, ; Nanjing, 210061 Jiangsu China
                [2 ]ISNI 0000 0001 2314 964X, GRID grid.41156.37, Department of Comparative Medicine, Jinling Hospital, , Nanjing University School of Medicine, ; Nanjing, 210002 Jiangsu China
                [3 ]ISNI 0000000119573309, GRID grid.9227.e, Shanghai Institute of Materia Medica, , Chinese Academy of Sciences, ; Shanghai, 201203 China
                [4 ]ISNI 0000 0004 1797 8419, GRID grid.410726.6, University of Chinese Academy of Sciences, ; Beijing, 100049 China
                [5 ]ISNI 0000 0001 2314 964X, GRID grid.41156.37, Department of Bioscience and Bioengineering, School of Chemistry and Life Science, , Jinling College of Nanjing University, ; Nanjing, 210061 Jiangsu China
                Author information
                http://orcid.org/0000-0001-9369-0263
                http://orcid.org/0000-0002-1303-1952
                Article
                56145
                10.1038/s41598-019-56145-z
                6928012
                31873149
                dcb148ab-4665-4967-9eaf-984b43f5f4b9
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 January 2019
                : 4 December 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81771890
                Award ID: 81672873
                Award Recipient :
                Funded by: the ‘Personalized Medicines—Molecular Signature-based Drug Discovery and Development’, Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. XDA12020108 One Hundred Talent Program of Chinese Academy of Sciences
                Funded by: The Beljanski Foundation
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                prostate,benign prostatic hyperplasia
                Uncategorized
                prostate, benign prostatic hyperplasia

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