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      Anti-Angiogenic Alternative and Complementary Medicines for the Treatment of Endometriosis: A Review of Potential Molecular Mechanisms

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          Abstract

          Endometriosis is caused by the growth or infiltration of endometrial tissues outside of the endometrium and myometrium. Symptoms include pain and infertility. Surgery and hormonal therapy are widely used in Western medicine for the treatment of endometriosis; however, the side effects associated with this practice include disease recurrence and menopause, which can severely influence quality of life. Angiogenesis is the main biological mechanism underlying the development of endometriosis. Numerous natural products and Chinese medicines with potent anti-angiogenic effects have been investigated, and the molecular basis underlying their therapeutic effects in endometriosis has been explored. This review aims to describe natural products and compounds that suppress angiogenesis associated with endometriosis and to assess their diverse molecular mechanisms of action. Furthermore, this review provides a source of information relating to alternative and complementary therapeutic products that mediate anti-angiogenesis. An extensive review of the literature and electronic databases, such as the China National Knowledge Infrastructure, PubMed, and Embase, was conducted using the keywords ‘endometriosis,' ‘traditional Chinese medicine,' ‘Chinese herbal medicine,' ‘natural compounds,' and ‘anti-angiogenic' therapy. Anti-angiogenic therapy is an emerging strategy for the treatment of endometriosis. Natural anti-angiogenic products and Chinese medicines provide several beneficial clinical effects, including pain relief. In this review, we summarize clinical trials and experimental studies of endometriosis using natural products and Chinese medicines. In particular, we focus on anti-angiogenic products and alternative and complementary medicines for the treatment of endometriosis and additionally examine their therapeutic efficacy and mechanisms of action. Anti-angiogenic natural products and/or compounds provide a new approach for the treatment of endometriosis. Future work will require randomized trials with larger numbers of subjects, as well as long-term follow-up to confirm the findings described here.

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          Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products.

          It is widely accepted that drug discovery often requires a systems-level polypharmacology approach to tackle problems such as lack of efficacy and emerging resistance of single-targeted compounds. Network pharmacology approaches are increasingly being developed and applied to find new therapeutic opportunities and to re-purpose approved drugs. However, these recent advances have been relatively slow to be translated into the field of natural products. Here, we argue that a network pharmacology approach would enable an effective mapping of the yet unexplored target space of natural products, hence providing a systematic means to extend the druggable space of proteins implicated in various complex diseases. We give an overview of the key network pharmacology concepts and recent experimental-computational approaches that have been successfully applied to natural product research, including unbiased elucidation of mechanisms of action as well as systematic prediction of effective therapeutic combinations. We focus specifically on anticancer applications that use in vivo and in vitro functional phenotypic measurements, such as genome-wide transcriptomic response profiles, which enable a global modelling of the multi-target activity at the level of the biological pathways and interaction networks. We also provide representative examples of other disease applications, databases and tools as well as existing and emerging resources, which may prove useful for future natural product research. Finally, we offer our personal view of the current limitations, prospective developments and open questions in this exciting field.
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            Anxiety and depression in patients with endometriosis: impact and management challenges

            Endometriosis is one of the most common gynecological diseases and affects ~10% of women in reproductive age. The most common clinical signs of endometriosis are menstrual irregularities, chronic pelvic pain (CPP), dysmenorrhea, dyspareunia and infertility. Symptoms of endometriosis often affect psychological and social functioning of patients. For this reason, endometriosis is considered as a disabling condition that may significantly compromise social relationships, sexuality and mental health. Considering this point, the aim of this narrative review is to elucidate the impact of anxiety and depression in the management of women with endometriosis. Psychological factors have an important role in determining the severity of symptoms, and women who suffer from endometriosis report high levels of anxiety, depression and other psychiatric disorders. In addition, endometriosis is one of the most important causes of CPP; women with endometriosis suffer from a wide range of pelvic pain such as dysmenorrhea, dyspareunia, nonmenstrual (chronic) pelvic pain, pain at ovulation, dyschezia and dysuria. Several studies have underlined the influence of CPP on quality of life and psychological well-being of women with endometriosis. Data suggest that the experience of pelvic pain is an important component of endometriosis and may significantly affect emotive functioning of affected women. It has been demonstrated that high levels of anxiety and depression can amplify the severity of pain. Further studies are needed to better understand the relationship between psychological factors and perception of pain. Treatment of endometriosis may be hormonal or surgical. Surgery is the primary treatment for more severe forms of endometriosis. There are few data in the literature about the influence of psychological factors and psychiatric comorbidities on the effectiveness of treatments. It is important to evaluate the presence of previous psychiatric diseases in order to select the most appropriate treatment for the patient.
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              The pains of endometriosis.

              Endometriosis is a disease defined by the presence of endometrial tissue outside of the uterus. Severe pelvic pain is often associated with endometriosis, and this pain can be diminished with therapies that suppress estrogen production. Many women with endometriosis also suffer from other chronic pain conditions. Recent studies suggest that mechanisms underlying these pains and sensitivity to estrogen involve the growth into the ectopic endometrial tissue of a nerve supply, which could have a varied and widespread influence on the activity of neurons throughout the central nervous system.
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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
                2018
                1 October 2018
                : 2018
                : 4128984
                Affiliations
                1Guangzhou University of Chinese Medicine, China
                2Team of Application of Chinese Medicine in Perioperative Period, Guangdong Provincial Hospital of Chinese Medicine, China
                3Department of Gynecology, Anyang Hospital of Traditional Chinese Medicine, China
                4Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, China
                Author notes

                Academic Editor: Victor Kuete

                Author information
                http://orcid.org/0000-0002-8177-4336
                http://orcid.org/0000-0001-6602-7730
                http://orcid.org/0000-0002-7351-7081
                http://orcid.org/0000-0002-4402-6160
                Article
                10.1155/2018/4128984
                6191968
                6906d7f9-9e34-4d0f-858a-f7980773adcc
                Copyright © 2018 Weilin Zheng 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
                : 29 May 2018
                : 15 August 2018
                : 29 August 2018
                Funding
                Funded by: Natural Science Foundation of Guangdong Province
                Award ID: 2014A030313400
                Funded by: National Natural Science Foundation of China
                Award ID: 81574008
                Funded by: Guangdong Science and Technology Department
                Award ID: 2014A020212278
                Award ID: 2013-137-154
                Funded by: Science and Technology Planning Project of Guangzhou municipal
                Award ID: 2014Y2-00048
                Categories
                Review Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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