The Chemistry Inside Spices & Herbs: Research and Development: Volume 3 E-Book
44,83 €
Mehr erfahren.
- Herausgeber: Bentham Science Publishers
- Kategorie: Wissenschaft und neue Technologien
- Serie: The Chemistry inside Spices & Herbs: Research and Development
- Sprache: Englisch
The Chemistry inside Spices & Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field.
Experts in phytochemistry have contributed reviews with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included.
Volume 3 covers several topics: the treatment of Polycystic Ovary Syndrome (PCOS), managing rheumatoid arthritis and related inflammatory conditions, orchid-derived natural flavoring and therapeutic agent Vanillin, Silymarin's utility in treating hepatic diseases, phytochemistry and pharmacological activities of Hygrophila spinosa, pharmacological and chemical aspects of Tulsi, Combretum caffrum as a potential anticancer molecule, and the roles of herbs in treating diabetes.
This book is an ideal resource for scholars (in life sciences, phytomedicine and natural product chemistry) and general readers who want to understand the importance of herbs, spices and traditional medicine in pharmaceutical R&D and clinical research.
Readership
Scholars in life sciences, phytomedicine and natural product chemistry; general readers who want to understand the importance of herbs, spices and traditional medicine, pharmaceutical R&D and clinical research.
The Chemistry inside Spices & Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field.
Das E-Book können Sie in Legimi-Apps oder einer beliebigen App lesen, die das folgende Format unterstützen:
Seitenzahl: 376
Veröffentlichungsjahr: 2024
Ähnliche
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
This is an agreement between you and Bentham Science Publishers Ltd. Please read this License Agreement carefully before using the ebook/echapter/ejournal (“Work”). Your use of the Work constitutes your agreement to the terms and conditions set forth in this License Agreement. If you do not agree to these terms and conditions then you should not use the Work.
Bentham Science Publishers agrees to grant you a non-exclusive, non-transferable limited license to use the Work subject to and in accordance with the following terms and conditions. This License Agreement is for non-library, personal use only. For a library / institutional / multi user license in respect of the Work, please contact: [email protected].
Usage Rules:
All rights reserved: The Work is the subject of copyright and Bentham Science Publishers either owns the Work (and the copyright in it) or is licensed to distribute the Work. You shall not copy, reproduce, modify, remove, delete, augment, add to, publish, transmit, sell, resell, create derivative works from, or in any way exploit the Work or make the Work available for others to do any of the same, in any form or by any means, in whole or in part, in each case without the prior written permission of Bentham Science Publishers, unless stated otherwise in this License Agreement.You may download a copy of the Work on one occasion to one personal computer (including tablet, laptop, desktop, or other such devices). You may make one back-up copy of the Work to avoid losing it.The unauthorised use or distribution of copyrighted or other proprietary content is illegal and could subject you to liability for substantial money damages. You will be liable for any damage resulting from your misuse of the Work or any violation of this License Agreement, including any infringement by you of copyrights or proprietary rights.Disclaimer:
Bentham Science Publishers does not guarantee that the information in the Work is error-free, or warrant that it will meet your requirements or that access to the Work will be uninterrupted or error-free. The Work is provided "as is" without warranty of any kind, either express or implied or statutory, including, without limitation, implied warranties of merchantability and fitness for a particular purpose. The entire risk as to the results and performance of the Work is assumed by you. No responsibility is assumed by Bentham Science Publishers, its staff, editors and/or authors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products instruction, advertisements or ideas contained in the Work.
Limitation of Liability:
In no event will Bentham Science Publishers, its staff, editors and/or authors, be liable for any damages, including, without limitation, special, incidental and/or consequential damages and/or damages for lost data and/or profits arising out of (whether directly or indirectly) the use or inability to use the Work. The entire liability of Bentham Science Publishers shall be limited to the amount actually paid by you for the Work.
General:
Any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims) will be governed by and construed in accordance with the laws of Singapore. Each party agrees that the courts of the state of Singapore shall have exclusive jurisdiction to settle any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims).Your rights under this License Agreement will automatically terminate without notice and without the need for a court order if at any point you breach any terms of this License Agreement. In no event will any delay or failure by Bentham Science Publishers in enforcing your compliance with this License Agreement constitute a waiver of any of its rights.You acknowledge that you have read this License Agreement, and agree to be bound by its terms and conditions. To the extent that any other terms and conditions presented on any website of Bentham Science Publishers conflict with, or are inconsistent with, the terms and conditions set out in this License Agreement, you acknowledge that the terms and conditions set out in this License Agreement shall prevail.Bentham Science Publishers Pte. Ltd. 80 Robinson Road #02-00 Singapore 068898 Singapore Email: [email protected]
PREFACE
VOLUME-3 of the book series “The Chemistry inside Spices and Herbs: Research and Development” is an excellent collection of nine chapters having extensive contents related to the detailed exploration of chemistry, pharmacology, and roles of different medicinally treasured plants (herbs and spices) and their constituents. All the chapters have been skilfully written by experts of the field. This book volume covers elaborated reviews on the chemistry and pharmacological properties of different medicinal plants viz. plants and herbal products in PCOS (Polycystic ovary syndrome), herbs in the management of rheumatoid arthritis and related inflammatory conditions, Orchid-derived natural flavoring and therapeutic agents’ (Vanillin and Vanilla) varied pharmaceutical applications, along with their roles in food industry, and fragrance industry, Silymarin in the treatment of hepatic disease, pharmacological properties of Hygrophila spinosa along with traditional applications, key diagnostic characteristics, and phytochemical profile, the pharmacological and chemical paradigms of Tulsi (Ocimum), chemistry and biological activity of isolated combretastatins from Combretum caffrum and current clinical status as anticancer medicines, herbs and spices to treat different cancers, and herbs in the treatment of diabetes.
In Chapter 1 written by Onder et al., with the most recent publications based on in vitro, preclinical, and clinical research as a novel viewpoint, a general assessment of the plants and herbal products in PCOS (Polycystic ovary syndrome) has been compiled from the preclinical and clinical point of view. Additionally, based on the ethnopharmacological characteristics of PCOS, traditional uses of the plants have also been assessed. With the hope of conducting herbs and developing new herbal-based products that are beneficial to PCOS, the impacts and underlying mechanisms of herbal medications used as a therapy for PCOS were also discussed.
In Chapter 2 written by Bharati et al., the function of medicinal plants, herbs, dietary supplements, and isolated bioactive compounds from plants in the treatment and management of rheumatoid arthritis is discussed, along with an explanation of how these substances work pharmacologically.
Chapter 3 written by Roy et al., highlighted the Vanilla’s varied applications in the food industry, fragrance industry, and pharmaceutical sector. This chapter may serve as a medium for interest in additional research into certain bioactive chemicals that will advance technical, scientific, and remedial values.
In Chapter 4 written by Singh et al., the potential of Silymarin in the treatment of hepatic disease has been discussed and explored.
Chapter 5 written by Satpathy et al., serves as a handy reference for traditional applications, key diagnostic characteristics, phytochemical profile, and pharmacological qualities of Hygrophila spinosa, which will be helpful to future researchers as they explore the plant's phytopharmacology through mechanistic research.
Chapter 6 written by Dobhal et al., has explored the pharmacological and chemical paradigms of Tulsi (Ocimum) present globally as it has been found to show the activity as antimicrobial, antimalarial, anthelmintic, anti-diarrheal, anti-oxidant, anti-mosquito agents, anti-inflammatory, chemo, and radio-protective, anti-cataract, cardio-protective, anti-hypertensive, anti-diabetic, antiseptic drugs, anti-hyperlipidemic, etc. in various studies.
Chapter 7 written by Patel et al., aimed to clarify the chemistry and biological activity of isolated combretastatins from Combretum caffrum as well as to examine their development, mode of action, research using computer-aided drug design, and current clinical status as anticancer medicines.
Chapter 8 by Agrawal et al., is centered on diabetes and accessible diabetic treatments, with a particular emphasis on herbal medicine and clinical trials of these herbal plants.
List of Contributors
Medicinal Plants including Spices for the Treatment of Polycystic Ovary Syndrome (PCOS) with a Preclinical-Clinical Perspective and Phytotherapeutic Approaches
Alev Onder1,*,Ozge Yilmaz1,Ahsen Sevde Cinar Koc1,2,Harun Kizilay3Abstract
Polycystic ovary syndrome (PCOS) is one of the most common metabolic-endocrine and multi-faceted gynecological disorders for reproductive-aged women. This condition has multiple undesirable effects with psychological, reproductive, and metabolic evidence. Multi-systemic adverse effects and conditions in PCOS cause irregular menstrual cycles, hirsutism, infertility, insulin resistance, diabetes, cardiovascular diseases, anxiety, depression, sexual dysfunctions, and eating disorders. PCOS symptoms are multi-faceted and alterable for each person, leading to different treatment methods evaluated from different perspectives. There are no definitive and ideal treatments for hormonal disorders-related clinical symptoms. Alternative therapies are also considered instead of commercially available drugs. In addition, alternative treatment methods have increased tremendously in recent years due to their minimal side effects. Since the therapies for PCOS require a multidisciplinary approach to understanding all aspects of this condition, medicinal plants should also be considered. The role of medicinal plants, including spices and their bioactive components, has been encouraged to prevent and treat PCOS, with new treatment strategies yielding promising results. Therefore, in this review, a general evaluation of the plants and herbal products in PCOS has been compiled from the preclinical and clinical point of view, with the current publications based on in vitro, preclinical, and clinical studies as a new perspective. Moreover, traditional usages of the plants, based on the ethnopharmacological aspects of PCOS, have been evaluated. The effects and underlying mechanisms of herbal medicines used as a remedy for PCOS were also reviewed with the expectation of herbs-spices and new herbal-based products that are effective on PCOS for future treatments.
INTRODUCTION
Natural products, including plants and phytochemicals, have desirable benefits for health [1] and are indispensable in treating and preventing diseases, ensuring the continuity of well-being in daily life. While natural products were used in the treatment of observation-based diseases in the past, with the advancement of technology, evidence-based treatment methods started to be used. However, phytotherapy, known as a treatment approach that includes medicinal plants in treating and preventing diseases, is attracting more and more attention than traditional knowledge from the past to the present [2]. Although conventional medicines are the first step in treating diseases, the global use and demand from markets of herbal remedies continue to increase rapidly. In addition, the use of medicinal plants in treating polycystic ovary syndrome (PCOS) have also been raised in this field. PCOS is an endocrine-gynecology disorder frequently emerging, especially in women of childbearing age; its prevalence reaches up to 20% and is accompanied by metabolic changes [3, 4]. Although the enhancement of prevalence is associated with modernization, it is thought that there is an argument that its history dates back to ancient times [5].
There are pharmacological and non-pharmacological treatment approaches for polycystic ovary syndrome, and the use of herbal medicines becomes popular, mainly due to the fewer side effects [6]. Therefore, this review aims to provide information on the definition, diagnosis, and etiology of PCOS. It comprehensively describes the internal and external factors that contribute to polycystic ovary syndrome, besides its history, epidemiology, and clinical findings focusing on its pharmacological and non-pharmacological treatments. Moreover, commonly prescribed drugs are also presented with complete drug information. In this process, several databases, including PubMed, Scopus, Google Scholar, and Science Direct, have been used for the literature survey. Keywords included treatment efficacy, polycystic ovary syndrome, PCOS, treatment, medicinal plants in PCOS, and phytochemicals in PCOS. Consequently, the important plant species are compiled in this chapter with various aspects and the literature approaching ethnopharmacological knowledge including studies of medicinal plants, bioactive components, and phytothe- rapeutics used for treating PCOS from the past to the present.
HISTORY AND EPIDEMIOLOGY OF POLYCYSTIC OVARY SYNDROME
Polycystic ovary syndrome, which has characteristic symptoms of polycystic ovary appearance in the ovary accompanied by amenorrhea, infertility, and hirsutism, was first described by Stein and Leventhal in 1935 [7]. Although it is known as “Stein-Leventhal Syndrome” in the literature, as defined in the past [8]. It is also a hormonal disorder for which there is evidence that it dates back to the Paleolithic and Neolithic ages [5]. PCOS was a multi-systemic disease whose diagnosis became more manageable with the rapid development of ultrasonography technology in the 1960s [9].
ETIOLOGY AND PATHOPHYSIOLOGY OF POLYCYSTIC OVARY SYNDROME
The etiology and pathophysiology of polycystic ovary syndrome remain obscured despite modern medical and scientific advances. However, genetic factors, lifestyle, prenatal androgen exposure, and environmental factors play primary role during the emergence of PCOS [10, 11].
The pathophysiological mechanisms (Fig. 1) are mainly hyperinsulinemia, alterations in gonadotropin-releasing hormone (GnRH), and androgen hormones [12]. Abnormal changes in GnRH secretion increase the luteinizing hormone (LH) secretion in the pituitary gland. For this reason, the ratio between LH and follicle-stimulating hormone (FSH) deteriorates.
Normal or low FSH levels increase the LH/FSH ratio. Thus, androgen release in theca cells (endocrine cells that make ovulation possible) in the stimulated ovary [13], ending with the appearance of hyperandrogenism (Fig. 2) [14-16]. In addition, the increase in the Anti-Müllerian hormone (AMH) may play a role in the formation of PCOS by causing an increase in LH levels by affecting the GnRH level [17].
The role of insulin in the pathophysiology of PCOS has been explained through various mechanisms. In the case of hyperinsulinemia, insulin causes abnormalities in gonadotropin secretion by acting on the hypothalamus. Increased LH induces androgen synthesis in ovarian theca cells [15, 18]. Besides, insulin induces an increase in free testosterone levels by affecting the synthesis of sex hormone-binding globulin (SHBG) protein in the liver [15, 19]. In addition, it increases the activity of cytochrome P450c17α, an important enzyme for synthesizing steroidal hormones, therefore increases androgen levels originating from the ovary and adrenal cortex [20].
Fig. (1)) The pathophysiological mechanisms of PCOS.One of the other possible pathophysiological mechanisms of insulin is caused by insulin resistance and hyperinsulinemia by interacting with insulin-like growth hormone-I (IGF-I) receptors in theca cells [18]. The clinical circumstances and the course of the disease worsen in PCOS patients accompanied by obesity. Therefore, it is absolutely necessary to understand the relationship between insulin resistance and hyperinsulinemia, obesity, and PCOS. Visceral adipocytes play a role in the metabolism of steroid hormones and are also affected by insulin resistance and hyperinsulinemia, causing abdominal obesity. Since obesity is known to cause hyperandrogenism, infertility, and other metabolic disorders, it is thought to be associated with PCOS-related complications [21]. Oxidative stress and low-level chronic inflammation are also directly or indirectly correlated with the pathophysiological mechanisms of PCOS [22, 23]. The periodontal inflammation and the microorganisms associated with this inflammation were also reported to be related to PCOS [24, 25]. Autoimmunity, a system of immune responses in which the organism creates antibodies against its healthy cells, tissues, and organs, can also be mentioned among the pathophysiological mechanisms of PCOS [26].
Fig. (2)) A simple representation of the differences between normal (A) and polycystic (B) ovaries in polycystic ovary syndrome.CLINICAL FINDINGS AND DIAGNOSIS OF POLYCYSTIC OVARY SYNDROME
A wide range of health authorities consider the Rotterdam criteria for the diagnosis of polycystic ovary syndrome. While at least one of the chronic anovulation and hyperandrogenism was sufficient criterion for the diagnosis of the disease in 1999, the presence of at least two of the oligo/anovulation, hyperandrogenism, and polycystic ovarian determinations was accepted as the expanded PCOS diagnostic criteria (Fig. 3) in 2003 [27]. The Rotterdam Criteria were further announced (in 2012) to identify four different phenotypes of PCOS. According to these recently determined criteria, the first phenotype includes hyperandrogenism, oligo-anovulation, and polycystic ovarian morphology; the second phenotype is hyperandrogenism and oligo-anovulation; the third one is hyperandrogenism and polycystic ovarian morphology; and finally, oligo-anovulation and polycystic ovarian morphology [16]. Although each phenotype leads to different results, it will be easier to understand the disease with phenotyping [28].
Phenotypic features frequently found in clinical findings are known as a result of hyperandrogenism. In a biochemical investigation, the testosterone, androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-sulfate (DHEA-S) hormones play a role in the formation of hyperandrogenism [29]. Hirsutism, one of the most common phenotypic findings, is defined as male-pattern hair growth caused by androgens acting on hair follicles [30]. Among the clinical findings that suggest that androgens play an important role, androgenetic alopecia, known as male pattern hair loss, is also observed [31]. The formation of acne, another symptom of polycystic ovary syndrome, is associated with increased sebum production induced by increased insulin, IGF-1, and androgens [32]. In addition to acne formation, “Acanthosis nigricans” is characterized by thickening brown plaques as a dermatological manifestation [33].
Fig. (3)) Symptoms of polycystic ovary syndrome.EFFECTS OF POLYCYSTIC OVARY SYNDROME ON QUALITY OF LIFE
Polycystic ovary syndrome is a disease with various side effects, primarily on the reproductive system. The metabolic and hormonal abnormalities in women with PCOS have been reported to increase the risk of infertility by causing ovulation disorders [34]. PCOS is associated with complications such as early miscarriage, preeclampsia during pregnancy, gestational diabetes, and preterm delivery [35, 36]. However, PCOS is not only a hormonal disorder that affects the reproductive system and fertility but also a process that causes the development of Type 2 diabetes, cardiovascular diseases, and cancer risk in the long term [37-41]. In particular, phenotypic changes resulting from hyperandrogenism are associated with the frequency of episodes of depression in women with polycystic ovary syndrome [42]. In addition to phenotypic changes, mechanisms involved in the pathophysiology of PCOS are thought to be associated with depression, anxiety, and mood disorders [43].
Considering all these complications, polycystic ovary syndrome definitely needs to be treated with a long-term and interdisciplinary approach [34].
PHARMACOLOGICAL AND NON-PHARMACOLOGICAL TREAT-MENT STRATEGIES IN POLYCYSTIC OVARY SYNDROME
The objectives of treatments of polycystic ovary syndrome can be listed as improving fertility in women with PCOS who wish to have children, alleviating the severity of phenotypic effects resulting from hyperandrogenism, and reducing metabolic syndrome and its associated risk factors [44, 45].
Although lifestyle modification is the first step of the treatment process, it is also accepted as the most effective treatment strategy for polycystic ovary syndrome, which requires long-term treatment [46]. Bariatric surgery emerges as an effective treatment method for improving fertility and reducing metabolic complications, especially in patients with PCOS who are accompanied by morbid obesity [47]. Combined oral contraceptives are frequently preferred in treatment modality for PCOS treatment to eliminate menstrual irregularities such as amenorrhea and oligomenorrhea and alleviate the severity of hirsutism and acne caused by hyperandrogenism [46]. These drugs contain estrogen and progestin, and in addition to eliminating menstrual irregularities, they also have a protective effect against endometrial cancers [45]. Cyproterone acetate, spironolactone, finasteride, and progestin derivative drospirenone are used in combination with oral contraceptives, especially in the alleviation of hirsutism as anti-androgens [43, 44]. Eflornithine hydrochloride used topically in hirsutism, influences hair follicle formation [44]. Flutamide, another anti-androgen effective agent, is not preferred because of its hepatotoxic effect [45].
Metformin (biguanide-derived) is a therapeutic agent that increases insulin sensitivity in treating Type 2 diabetes and helps regulate the metabolic and hormonal condition in PCOS treatment [48]. Other therapeutic agents that increase insulin sensitivity, such as pioglitazone and rosiglitazone (thiazolidinediones), are also used to treat PCOS to improve fertility and positively affect other conditions in metabolic parameters [49].
With an antiestrogenic effect, clomiphene citrate induces ovulation in polycystic ovary syndrome patients who want a child [46]. If ovulation does not occur within the expected time, the patient is considered resistant to clomiphene citrate [50]. Letrozole, an aromatase inhibitor or exogenous FSH, induces ovulation in these patients [44, 46]. In some clomiphene-resistant cases, ovulation induction is provided by applying a surgical method-Laparoscopic Ovarian Drilling (LOD). In addition, it aims to prevent complications that may occur during pregnancy [51]. In vitro fertilization method (IVF) is considered in patients who do not have ovulation induction despite all the previously attempted options [52]. Probiotics and synbiotics for three months or longer in treating PCOS benefit metabolic, inflammatory, and hormonal parameters and clinical profiles [53].
There are various side effects of drugs and surgical methods used for conventional treatment. For example, fatal venous thromboembolism in treatment with combined oral contraceptives [44]; vitamin B12 deficiency, gastrointestinal complaints, and lactic acidosis in metformin therapy [48]. In bariatric surgery, hormonal changes during the transition to menopause and vitamin D deficiency [47] can be considered among the side effects mentioned.
THE ROLE of MEDICINAL PLANTS IN THE TREATMENT of POLYCYSTIC OVARY SYNDROME
Side effects caused by pharmacological and surgical treatments in polycystic ovary syndrome treatment have increased the interest of scientists and consumers in natural products and medicinal plants. It is thought that medicinal plants or their bioactive components may effectively improve clinical aspects and prevent many complications by affecting pathophysiological mechanisms [54].
In this context, the tendency toward alternative treatments in many parts of the world and the increasing return to nature have increased the use of plants and herbal products in many diseases, including polycystic ovary syndrome. Therefore, this review has discussed various medicinal plants and herbal products that are effective in PCOS symptoms.
ETHNOPHARMACOLOGICAL APPROACH
Plants utilized to treat many diseases, including reproductive system diseases in many cultures from ancient times to the present, have an essential place in traditional treatment strategies. There are herbal mixtures, single plant, and monomer treatment with phytomolecules for polycystic ovary syndrome treatments [55, 56]. The formulations, especially of Traditional Chinese Medicine (TCM), Traditional Korean Medicine (TKM), and Traditional Eastern Medicine (TEM) are gathered in Table 1.
Herbal prescriptions used in polycystic ovary syndrome prepared according to TCM attract attention within all alternative medicine approaches, as shown in Table 1. Tiangui Fang [57] and Bushen Tongmai [58] found that TCM prescriptions regulated glucose metabolism and induced ovulation in a study. Cangfu Daotan decoction has a positive effect on hyperinsulinemia [55, 59, 60]. In addition, identification studies of the biological pathway have also been conducted with Cangfu Daotan decoction [61]. In another study, the effects of Zigui decoction [62] and the Danzhi Xiaoyao tablet were reported to have healing effects in treating symptoms related to PCOS [63].
Moreover, clinical studies have been carried out to observe the hormonal effects of the formulations. Longdan Xiegan, Heqi San, and Zhibaidihuang formulations have been reported to provide hormonal regulation in PCOS patients [64-66]. The Jinfeng pill and FuFang ZhenZhu Tiao Zhi prescription have positively affected ovarian function and morphology [67-69]. As a result of a study on TCM prescriptions in Taiwan, more than half of the women who suffered from PCOS preferred TCM treatment for infertility or menstrual disorders. Jia-wei-xiao-yao-san, Wen-jing-tang, and Gui-zhi-fu-ling-wan are the most used formulations in this field [70].
HemoHIM, an herbal mixture used in Traditional Korean Medicine [71], and IMOD (selenium-based) prescription used in Traditional Eastern Medicine reduced cystic follicles and supported the development of the corpus luteum [72]. In another study, induction of the estrous cycle was reported in treatment with the Kyung-Ok-Ko prescription [73]. A mixture of “DXB-2030”, one of Eastern Medicine's prescriptions, was demonstrated to reverse testosterone propionate-induced changes [74].
In addition to herbal mixtures, some plants are used in a single form in treatment. For example, cinnamon regulates glucose metabolism [75] and Labisia pumila var. alata reduces both glucose and cholesterol levels [76]. In another study, Matricaria chamomilla and Linum usitatissimum were reported to reduce the number of cystic follicles [77, 78]. Aloe vera and Cocos nucifera are the plants used to decrease cholesterol levels for polycystic ovary syndrome patients [79-81]. Atractylodes macrocephala [82]; Zingiber officinale [83], and Phyllanthus muellerianus have effectively regulated the menstrual cycle by providing positive hormonal changes [84]. Ulmus minor bark is used in Traditional Persian Medicine to increase women's fertility [85], and in Taiwan, the three most important recipes with a single herb species listed as Yi-mu-cao (Herba Leonuri), Xiang-fu (Rhizoma Cyperi), and Tu-si-zi (Semen Cuscutae) [70].
IN VITRO STUDIES ON POLYCYSTIC OVARY SYNDROME
Cinnamic acid [86], platonic acid in the roots of Platycodi grandiflorum [87], hypaphorine [88] in Caragana korshinskii, Labisia pumila var. alata extract [89], the methanol and water extracts of Leonurus sibiricus [90], Citrus limon [91], berberine [92], the saponin-rich fraction of ethanol extract of Momordica charantia seeds [93] and aqueous extract of Costus pictus leaves [94], have exhibited in vitro positive effects on insulin resistance. The protective effect of procyanidin oligomers in the composition of Cinnamomum tamala and C. cassia extracts on pancreatic β cells has also been reported [95].
Nepodin in Rumex japonicus roots [96], ethyl acetate fractions of Physalis alkekengi fruits and aerial parts [97], Cimicifuga racemosa extract coded as Ze450 [98], Phyllanthus emblica, Tinospora cordifolia, and Curcuma longa [99] have antidiabetic effects, most likely effective in PCOS.
The aqueous-alcoholic extract of Achillea santolina [100], salidroside isolated from Rhodiola rosea [101], resveratrol [102], genistein-8-C-glucoside in low doses [103], anthocyanins from Malus sieversii [104], the aqueous-alcoholic extract of Passiflora nitida leaves [105], and the active ingredient cryptotanshinon obtained from the root extract of Salvia miltiorrhiza have antioxidant effects [106]. Also, Aloe vera extract increases the mRNA expression of antioxidant enzymes [107].
Isoflavones of Cicer arientinum [108], phenolic compounds of the aerial part of Alchemilla millefolium [109], alpinumisoflavone and abyssinone V-4′-methyl-ether of Erythrina lysistemon [110], Asplenium trichomanes leaf extracts [111] showed estrogenic activity.
In another study, the methanolic extract of Ecklonia cava [112], Nardostachys jatamansi, Tribulus terrestris, and Embelia tsjeriam-cottam [113], and flavonoids from the methanolic extract of Sophora flavescens [114] have been noted to have in vitro anti-androgenic activities.
IN VIVO STUDIES ON POLYCYSTIC OVARY SYNDROME
Preclinical Studies on Extracts
In a study, Tephrosia purpurea dried seeds (200 mg/kg) improved the estrus cycle by 80% [115]. Moringa oleifera leaf extract was administered orally to rats suffering from insulin resistance and polycystic ovary syndrome. As a result of administration, M. oleifera leaf extract (250 and 500 mg/kg) impressed insulin levels and increased folliculogenesis compared to metformin [116]. A standardized extract rich in quassinoids (TAF 273, 50 mg/kg) prepared from the roots of Eurycoma longifolia had a curative effect on the functional disorders caused by testosterone exposure in rats. The curative effects could be related to eurycomanone, and 13α,21 dihydrouricomanone [117]. In another study, an herbal tea (40 g/L) prepared with Mentha piperita possessed an antioxidant effect on PCOS-induced rats. Also, significant improvements in testosterone, estrogen, and LH levels, as well as in the ovary and uterine tissues, have been observed [118]. In addition, the aqueous-alcoholic extract prepared from the fruits of Citrullus colocynthis combined with metformin has a synergistic effect on the improvement of follicle morphology due to the suppression of the pro-inflammatory process by flavonoid derivatives [119]. In a preclinical study, a formulation including Aloe vera gel (1 mL=10 mg) was administered orally, and LDL and plasma triglyceride levels decreased significantly. In contrast, HDL levels increased due to the polyphenols and phytosterols in the plant [80]. Cinnamon powder (10 mg/100 g) was administered orally to experimental animals with PCOS. This process decreases the levels of cinnamon extract IGF-I (insulin-like growth factor-I) in the ovary and plasma while increasing the level of insulin-like growth factor-binding protein (IGFBP-I), which reduces insulin resistance in PCOS and has positive effects on symptoms [120]. Nerve growth factor (NGF), a neurotrophin, is thought to be associated with PCOS [121]. An increased NGF and NGF mRNA expression was significantly reduced when a red Korean ginseng extract (200 mg/kg) was administered to estradiol valerate-induced PCOS rat ovaries [122]. In another study, Calligonum extract (20 mg/kg) had favorable effects on fertility by significantly increasing the total antioxidant capacity in the ovaries of experimental animals [123].
Other preclinical studies on plant extracts and polycystic ovary syndrome are summarized in Table 2. Kakadia et al. (2019) revealed that the similar pharmacological effects on PCOS of different extracts prepared from the same part of the same plant species might be due to the different flavonoid content and amounts of the extracts [124]. The total extract (100 mg/kg) from Ocimum kilimandscharicum leaves, and the ethyl acetate fraction (100 mg/kg) obtained from the whole extract were investigated for the curative effect of PCOS symptoms in experimental animals. The results indicated it might be more effective than Metformin, frequently used to treat PCOS [125]. Moreover, Mentha spicata (40 mg/kg) and Linum usitatissimum (200 mg/kg) extracts, which are known to have curative effects on PCOS, are more effective when used in combination [126].
Preclinical Studies on Bioactive Phytochemicals
Studies on medicinal plants and phytochemicals from plants regarding polycystic ovary syndrome treatment have been available in various publications. Therefore, preclinical studies and related literature information are depicted in Table 3.
