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Adaptogenic Theory and Korean Ginseng ( Panax ginseng C.A. Meyer)

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Withania somnifera L. Dunal (Ashwagandha), a key medicinal plant native to India, is used globally to manage various ailments. This review focuses on the traditional uses, botany, phytochemistry, and pharmacological advances of its plant-derived constituents. It has been reported that at least 62 crucial and 48 inferior primary and secondary metabolites are present in the W. somnifera leaves, and 29 among these found in its roots and leaves are chiefly steroidal compounds, steroidal lactones, alkaloids, amino acids, etc. In addition, the whole shrub parts possess various medicinal activities such as anti-leukotriene, antineoplastic, analgesic, anti-oxidant, immunostimulatory, and rejuvenating properties, mainly observed by in vitro demonstration. However, the course of its medical use remains unknown. This review provides a comprehensive understanding of W. somnifera, which will be useful for mechanism studies and potential medical applications of W. somnifera, as well as for the development of a rational quality control system for W. somnifera as a therapeutic material in the future.
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The reductionist concept, based on the ligand–receptor interaction, is not a suitable model for adaptogens, and herbal preparations affect multiple physiological functions, revealing polyvalent pharmacological activities, and are traditionally used in many conditions. This review, for the first time, provides a rationale for the pleiotropic therapeutic efficacy of adaptogens based on evidence from recent gene expression studies in target cells and where the network pharmacology and systems biology approaches were applied. The specific molecular targets and adaptive stress response signaling mechanisms involved in nonspecific modes of action of adaptogens are identified.
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Background: Sustained stress with the overproduction of corticosteroids has been shown to increase reactive oxygen species (ROS) leading to an oxidative stress state. Mitochondria are the main generators of ROS and are directly and detrimentally affected by their overproduction. Neurons depend almost solely on ATP produced by mitochondria in order to satisfy their energy needs and to form synapses, while stress has been proven to alter synaptic plasticity. Emerging evidence underpins that Rhodiola rosea, an adaptogenic plant rich in polyphenols, exerts antioxidant, antistress, and neuroprotective effects. Methods: In this study, the effect of Rhodiola rosea extract (RRE) WS®1375 on neuronal ROS regulation, bioenergetics, and neurite outgrowth, as well as its potential modulatory effect on the brain derived neurotrophic factor (BDNF) pathway, was evaluated in the human neuroblastoma SH-SY5Y and the murine hippocampal HT22 cell lines. Stress was induced using the corticosteroid dexamethasone. Results: RRE increased bioenergetics as well as cell viability and scavenged ROS with a similar efficacy in both cells lines and counteracted the respective corticosteroid-induced dysregulation. The effect of RRE, both under dexamethasone-stress and under normal conditions, resulted in biphasic U-shape and inverted U-shape dose response curves, a characteristic feature of adaptogenic plant extracts. Additionally, RRE treatment promoted neurite outgrowth and induced an increase in BDNF levels. Conclusion: These findings indicate that RRE may constitute a candidate for the prevention of stress-induced pathophysiological processes as well as oxidative stress. Therefore, it could be employed against stress-associated mental disorders potentially leading to the development of a condition-specific supplementation.
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Background: In the 1960s, research into plant adaptogens began. Plants with adaptogenic properties have rich phytochemical compositions and have been used by humanity since ancient times. However, it is not still clear whether the adaptogenic properties are because of specific compounds or because of the whole plant extracts. The aim of this review is to compare the bioactive compounds in the different parts of these plants. Methods: The search strategy was based on studies related to the isolation of bioactive compounds from Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus, and Panax ginseng. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Results: This review includes data from 259 articles. The phytochemicals isolated from Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus, and Panax ginseng were described and classified in several categories. Conclusions: Plant species have always played an important role in drug discovery because their effectiveness is based on the hundreds of years of experience with folk medicine in different nations. In our view, there is great potential in the near future for some of the phytochemicals found in these plants species to become pharmaceutical agents.
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In China, Japan, and Korea, Panax ginseng has been used in traditional medicine for thousands of years. Panax is a plant used as a general tonic or adaptogen for chronically ill patients. The current study evaluated the cytotoxicity of Panax ginseng extract (PGE). Different cell lines (HCT-116, LNCaP, and normal cell line VERO) were treated with different inhibitory agentsat different concentrations (1000, 500, 250, 125, 62.5, and 31.25 µg/ml) as follows: G1 (Methanol Panax ginseng extract, PGE), G2 (Doxorubicin, DOX), and G3 (Methanol Panax ginseng extract +DOX, PDD). Each inhibitory agent group was used to treat the cancerous cell lines HCT-116, LNCaP, and normal cell line (VERO) to obtain IC50% by MTT assay. The inhibitory ability of the 1000 μg/ml PGE was significantly increased in all the three-cell lines compared with other concentrations. The recorded data revealed that the inhibition ability of PGE and Doxorubicin towards the HCT-116 cell line significantly increased compared with the other cell lines. The interaction between different PGE concentrations and cell lines showed that the 1000 μg/ml PEG had the highest inhibitory effects on HCT-116 compared with other combinations. The interaction between different DOX concentrations and different types of cell lines showed that the 1000 μg/ml DOX had the highest inhibitory effects on LNCap compared with other combinations. The PGD inhibition ability reflected a significantly higher difference toward the HCT-116 cell line as compared with other cell lines. IC50% is the concentrations (µg/ml) to kill 50% of cell line. It was calculated by MTT assay for three cell lines: HCT-116, LNCaP, and VERO. The rate of effectiveness of the inhibitory factors (PGE, DOX, and PGD) showed highly significant differences toward the cell line HCT-116 compared to the other cell lines. This indicates the safety of the PGE compound and its low toxicity toward normal cells, quite the opposite of cancer cells as compared to the common drug DOX and combined PGD (PGE+DOX). PGD combined with DOX (PGE + DOX) showed antagonistic results toward the HCT116, LNCaP, and VERO cell lines, while UDE combined with DOX (UDE+DOX) showed synergistic activity.
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Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or loss of concentration, and during recovery. According to ancient records, red ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their levels in blood is low-at concentrations from 10 −6 to 10 −18 M. In the present study, we compared the effects of red ginseng root preparation HRG80 TM (HRG) at concentrations from 0.01 to 10,000 ng/mL with effects of white ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression in isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up-or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially varied effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10,000 to 0.01 ng/mL. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.
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Background and aim: Brain health is becoming more important to the average person as the number of people with cognitive impairments, such as Alzheimer's disease (AD), is rising significantly. The current Food and Drug Administration-approved pharmacotherapeutics for dementia neither cure nor halt cognitive decline; they just delay the worsening cognitive impairment. This narrative review summarizes the effects of nutrients and phytonutrients on cognitive function. Methods: A comprehensive literature search of PubMed was performed to find clinical trials in humans that assessed the effects of nutrients and phytonutrients on cognitive function published in English between 2000 and 2021. Six independent reviewers evaluated the articles for inclusion in this review. Results: Ninety-six articles were summarized in this narrative review. In total 21 categories of nutrients and phytonutrients were included, i.e., α-lipoic acid, Bacopa monnieri, B vitamins, cholinergic precursors, vitamin D, vitamin E, Ginkgo biloba, ginseng, lion's mane mushroom, N-acetyl cysteine, omega-3 fatty acids, aloe polysaccharides, Rhodiola rosea, rosemary, saffron, tart cherries, turmeric, wild yam, Withania somnifera, xanthines, and zinc. Particular noteworthy effects on cognition included memory, recollection, attention, intelligence, vocabulary, recognition, response inhibition, arousal, performance enhancement, planning, creative thinking, reaction time, vigilance, task switching, orientation to time, place, and person, reading, writing, comprehension, accuracy, learning, information processing speed, executive function, mental flexibility, daily functioning, decrease in mental fatigue, and freedom from distractibility. Some nutrients and phytonutrients also improved mood and contentedness and reduced anxiety and the need for caregiving. These effects are not completely consistent or ubiquitous across all patient populations or health statuses. Adverse effects were minimal or nonexistent. Conclusion: Due to the growing population of people with cognitive impairment and the lack of effective pharmacotherapeutics, it is prudent for those afflicted or their caregivers to find alternative treatments. Our narrative review shows that many of these nutrients and phytonutrients may be promising for treating some aspects of cognitive impairment, especially for people afflicted with AD. Relevance for patients: As demonstrated in a number of clinical trials, healthy adults and patients with various health challenges (e.g., AD, mild cognitive impairment, multiple sclerosis, and Parkinson's disease) exhibiting a wide range of severity in cognitive defects would be best served to consider multiple nutrients and phytonutrients to improve aspects of their cognitive function.
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Adaptogens are synthetic compounds (bromantane, levamisole, aphobazole, bemethyl, etc.) or plant extracts that have the ability to enhance the body’s stability against physical loads without increasing oxygen consumption. Extracts from Panax ginseng, Eleutherococcus senticosus, Rhaponticum carthamoides, Rhodiola rosea, and Schisandra chinensis are considered to be naturally occurring adaptogens and, in particular, plant adaptogens. The aim of this study is to evaluate the use of plant adaptogens in the past and now, as well as to outline the prospects of their future applications. The use of natural adaptogens by humans has a rich history—they are used in recovery from illness, physical weakness, memory impairment, and other conditions. About 50 years ago, plant adaptogens were first used in professional sports due to their high potential to increase the body’s resistance to stress and to improve physical endurance. Although now many people take plant adaptogens, the clinical trials on human are limited. The data from the meta-analysis showed that plant adaptogens could provide a number of benefits in the treatment of chronic fatigue, cognitive impairment, and immune protection. In the future, there is great potential to register medicinal products that contain plant adaptogens for therapeutic purposes.
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Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adapto-gens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential Med Res Rev. 2020;1-74. wileyonlinelibrary.com/journal/med | 1 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Background: Ginseng has a long history of widespread use and remarkable effects as traditional medicine, adjuvant and dietary supplement. The therapeutic value, diverse functionalities and rapid development of ginseng have driven a significant increase in the number of ginseng clinical trials, ranging from its use in various ailments, formulation to safety concerns. Despite the persistent interest in ginseng clinical research, the medical effectiveness of ginseng is inconclusive and there is a lack of bibliometric analysis of the hundreds of ginseng clinical trials. Aim of review: This review aims to provide an extensive overview of ginseng clinical trials over the past 40 years (1979-2018) in combination with a qualitative and quantitative analysis. The annual clinical trial analysis of time distribution, country and institution network analysis for space cooperation, statistical analysis for various functions, as well as efficiency and effect size were performed for global ginseng clinical trials. Besides, preparation categories, administration routes, and the safety of ginseng clinical trials were also investigated. Key scientific concepts of review: The 40-year journey of ginseng clinical trials has experienced emerging, boom, and stable or transitional stages. The global network of ginseng clinical trials has relevant regional distribution in Asia, North America and Europe. South Korea makes a great contribution to building up large research clusters and strong cooperation links. Universities are the key contributors to ginseng clinical trials. The development of ginseng products could be focused on the clinical trial in diseases with higher effectiveness or effect size, such as sexual function and cognitive & behavior and require rigorous investigations and evidence to evaluate safety. More attention should be paid to different effects from different preparations. We believe this review will provide new insights into the understanding of global ginseng clinical trials and identifies potential future perspectives for research and development of ginseng.
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Background Herbal adaptogens are plant medicines which have traditional associations with herbal ‘tonics’ and promote homeostasis and non-specifically increase resistance to stress. Current definitions of adaptogens have been derived from extensive laboratory research, however there has not been sufficient clinical data for the concept to be standardised by regulatory bodies in Europe or Australia, nor is there clarity around how adaptogens are used and understood by herbalist clinicians themselves. This study aimed to identify how Australian Naturopaths measure adaptogenic activity relative to the clinical outcomes they aim to achieve. Methods A qualitative methodology was implemented using focus groups and thematic analysis. Results Three focus groups were conducted with a total of 17 Naturopaths with a Bachelor degree or higher qualification and over five years clinical experience. Three core themes for identified: ambiguous cultural origins with divergent perceptions on sources of knowledge about adaptogens; raising vitality and having a restorative effect, and intersystem activity. Within these three central themes a number of sub-themes were identified. Conclusion Naturopathic clinicians utilise both subjective and objective measures of vitalistic signs across multiple body systems, however, the current available research may not accurately reflect expert clinician understanding and use of adaptogens. The study opens pathways to developing novel approaches to measuring adaptogenic activity which may facilitate the process of international standardisation of the adaptogenic concept for the development of well-designed clinical studies.
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Background: The aim of this pilot study was to compare the efficacy of hydroponically cultivated red Panax ginseng Meyer root preparation (HRG80) and traditionally harvested six-year-old white P. ginseng standard preparation (PGS) with placebo in preventing symptoms of stress. Methods: The effects of HRG80, PGS, and placebo capsules were studied in 50 tired healthy subjects in a three-arm, randomized, double-blinded, placebo-controlled crossover trial. Efficacy-outcome measures included the accuracy of processing the d2 test for cognitive functions, obtained accuracy score in a computerized memory test, and the perceived-stress (PS) score. Results: A statistically significant interaction effect between time and treatment (p < 0.0001) was observed in the attention d2 and memory tests, indicating that HRG80 treatment was more beneficial than that with a placebo. The effects of PGS were better than those of the placebo, but the difference was not statistically significant. There was significant difference between the effects of HRG80 and PGS (p < 0.0001) that were observed after single (Day 1) and repeated administrations on Days 5 and 12 of treatment. Conclusion: Overall, HRG80 treatment was significantly superior compared to that with the PGS and placebo regarding attention, memory, and PS scores after single and repeated administrations for 5 and 12 days.
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Background: Existed mathematical models of individual adaptation are mostly reductionist by nature. Researchers usually a priori consider the subject adapted basing only on the fact of continued or prolonged influence of the harmful factor. This paper describes a method that allows assessing the physiological adaptedness to experimental challenges on the basis of holistic approach and quantitative criteria. Methods: The suggested method comprises simple equations and incorporates into the model an indicator that differentiates functions in regard to their significance for determining physiological adaptedness considered as an outcome of the adaptive process. Results: The proposed empirical model affords the possibility of comparing subjects in respect to their resistance to several loads. Physiological parameters were differentiated with regard to their significance for assessing adaptedness. Two examples of animal adaptation to exercise after physical training and plant adaptogen administration are considered. Conclusion: The calculated index of adaptedness is useful in that it replaces wordy descriptions of large tables that reveal alterations in numerous parameters of many subjects under study.
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Background: Phytoadaptogens are considered to be herbal medicines with a multi-target effect that strengthen organ systems compromised by stress. Although animal and laboratory studies have identified numerous molecular targets associated with adaptogenic activity, the non-specific characteristic of these herbal medicines has meant there is no known methods to accurately determine efficacy of adaptogens in humans. This critical review of the evidence aims to identify domains which have been used to measure the effect of adaptogens in humans, in order to create pathways for translating laboratory, animal, and clinical studies on adaptogens into practical applications in the future. Methods: EMBASE, AMED, PubMed, Cochrane Library, and WHO ICTRP databases were searched for randomized trials which examined known physiological actions of adaptogens. Results: Twenty-four studies were identified and critically appraised using the Jadad scale. The findings identified three broad categories of outcome measures, including cognitive, mood and biological measures. Conclusions: There was a great heterogeneity in data making it difficult to draw conclusions as to the most effective measurement tools to capture the holistic activity in humans. Cognitive measures hold promise as a reliable measurement tool when used in conjunction with other relevant tools. Further investigation is necessary to determine the most appropriate and diverse tools to measure the complex multi-target action of adaptogens.
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Abstract Modern studies have shown that adaptogens can non-specifically enhance the resistance of human body under a wide range of external stress conditions with a multi-targeted and multi-channel network-like manner, especially by affect the immune-neuro-endocrine system and the hypothalamic–pituitary–adrenal axis. This review article draws the attention to the relationships of adaptogens, tonics from traditional Chinese medicine (TCM) and ginseng-like herbs worldwide, which all have similar plant sources and clinical applications. To clarify the sources and pharmacological mechanisms of these plant-originated adaptogens, which will provide useful information for the utilization of adaptogens to improve the human health. Meanwhile, the TCMs and the world-wide ginseng-like herbs from each region’s ethnopharmacology will be beneficial modernization and globalization.
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Introduction: Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. Aim of the study: The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, and Bryonia alba. Materials and methods: To investigate the underlying molecular mechanisms of adaptogens, we conducted RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of adaptogens and analyzed the relevance of deregulated genes to adaptive stress-response signaling pathways using in silico pathway analysis software. Results and discussion: At least 88 of the 3516 genes regulated by adaptogens were closely associated with adaptive stress response and adaptive stress-response signaling pathways (ASRSPs), including neuronal signaling related to corticotropin-releasing hormone, cAMP-mediated, protein kinase A, and CREB; pathways related to signaling involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin–angiotensin, AMPK, calcium, and synapses; and pathways associated with dendritic cell maturation and G-coupled protein receptor–mediated nutrient sensing in enteroendocrine cells. All samples tested showed significant effects on the expression of genes encoding neurohormones CRH, GNRH, UCN, G-protein–coupled and other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, transmembrane channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, protein kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, a chaperone (HSPA6), and other proteins, all of which modulate numerous life processes, playing key roles in several canonical pathways involved in defense response and regulation of homeostasis in organisms. It is for the first time we report that the molecular mechanism of actions of melatonin and plant adaptogens are alike, all adaptogens tested activated the melatonin signaling pathway by acting through two G-protein–coupled membrane receptors MT1 and MT2 and upregulation of the ligand-specific nuclear receptor RORA, which plays a role in intellectual disability, neurological disorders, retinopathy, hypertension, dyslipidemia, and cancer, which are common in aging. Furthermore, melatonin activated adaptive signaling pathways and upregulated expression of UCN, GNRH1, TLR9, GP1BA, PLXNA4, CHRM4, GPR19, VIPR2, RORA, STAT5A, ZFPM2, ZNF396, FLT1, MAPK10, MERTK, PRKCH, and TTN, which were commonly regulated by all adaptogens tested. We conclude that melatonin is an adaptation hormone playing an important role in regulation of homeostasis. Adaptogens presumably worked as eustressors (“stress-vaccines”) to activate the cellular adaptive system by inducing the expression of ASRSPs, which then reciprocally protected cells from damage caused by distress. Functional investigation by interactive pathways analysis demonstrated that adaptogens activated ASRSPs associated with stress-induced and aging-related disorders such as chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, metabolic disorders, and cancer. Conclusion: This study has elucidated the genome-wide effects of several adaptogenic herbal extracts in brain cells culture. These data highlight the consistent activation of ASRSPs by adaptogens in T98G neuroglia cells. The extracts affected many genes playing key roles in modulation of adaptive homeostasis, indicating their ability to modify gene expression to prevent stress-induced and aging-related disorders. Overall, this study provides a comprehensive look at the molecular mechanisms by which adaptogens exerts stress-protective effects.
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Ginseng has been traditionally used for several millennia in Asian countries, including Korea, China, and Japan, not only as a nourishing and tonifying agent but also as a therapeutic agent for a variety of diseases. In recent years, the various effects of red ginseng including immunity improvement, fatigue relief, memory improvement, blood circulation improvement, antioxidation, mitigation of menopausal women's symptoms, and anticancer an effect have been reported in clinical as well as basic research. Around the world, there is a trend of the rising consumption of health functional foods on the level of disease prevention along with increased interest in maintaining health because of population aging and the awareness of lifestyle diseases and chronic diseases. Red ginseng occupies an important position as a health functional food. But till now, international ginseng monographs including those of the World Health Organization have been based on data on white ginseng and have mentioned red ginseng only partly. Therefore, the red ginseng monograph is needed for component of red ginseng, functionality certified as a health functional food in the Korea Food and Drug Administration, major efficacy, action mechanism, and safety. The present red ginseng monograph will contribute to providing accurate information on red ginseng to agencies, businesses, and consumers both in South Korea and abroad.
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Although ginseng has long been broadly used in clinical settings around the world, few clinical trials on ginseng have been conducted. The objective of this study was to provide a comprehensive evaluation of the characteristics of ginseng clinical trials registered in the WHO International Clinical Trials Registry Platform (ICTRP) as of December 2017 regarding their frequency, design, type of ginseng, dosage, duration, condition, funding sources, and publication status. A total of 134 ginseng clinical studies were registered from 2002 to 2017, of which 60.4% were completed and 23.1% are actively recruiting participants. A large number of trials were associated with aspects of high-quality trial design. Overall, 94% of the trials employed randomized allocation to study arms, 78.4% were double-blind studies using placebo as one of the control groups, and 71% were published as completed trials. Trials whose sample size was restricted to fewer than 100 participants accounted for 74.7% of the total. Of the primary funding sources for ginseng studies, 67.2% were nonindustry organizations. The ginseng clinical trials were heterogeneous with respect to ginseng species and variety, indications, dose, duration, and participant characteristics. Clearly, stricter and methodologically suitable studies are needed to demonstrate the efficacy and safety of ginseng.
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Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of "adaptability" and the adaptogenic activity of adaptogens. Here, I demonstrate that (1) the mechanisms of action of adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing adaptogen function and are applicable to any phytochemical. Molecular targets, signaling pathways, and networks common to adaptogens have been identified. They are associated with stress hormones and key mediators of the regulation of homeostasis. In this context, the mechanisms of action of adaptogens are specifically related to stress-protective activity and increased adaptability of the organism. Consequently, adaptogens exhibit polyvalent beneficial effects against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer, and other aging-related diseases. Current and potential uses of adaptogens are mainly related to stress-induced fatigue and cognitive function, mental illness, and behavioral disorders. Their prophylactic use by healthy subjects to ameliorate stress and prevent age-related diseases appears to be justified. It is very unlikely that the pharmacological activity of any phytochemical is specific and associated only with one type of receptor, particularly adaptogenic compounds, which affect key mediators of the adaptive stress response at intracellular and extracellular levels of communication.
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Background: Estrogen signaling pathways are modulated by exogenous factors. Panax ginseng exerts multiple activities in biological systems and is classified as an adaptogen. Zearalenol is a potent mycoestrogen that may be present in herbs and crops arising from contamination or endophytic association. The goal of this study was to investigate the impact of P. ginseng, zearalenol and estradiol in tests on spermatozoal function. Methods: The affinity of these compounds for estrogen receptor (ER)-alpha and beta (ERα and ERβ)-was assessed in receptor binding assays. Functional tests on boar spermatozoa motility, movement and kinematic parameters were conducted using a computer-assisted sperm analyzer. Tests for capacitation, acrosome reaction (AR), and chromatin decondensation in spermatozoa were performed using microscopic analysis. Results: Zearalenol-but not estradiol (E2)- or ginseng-treated spermatozoa-decreased the percentage of overall, progressive, and rapid motile cells. Zearalenol also decreased spontaneous AR and increased chromatin decondensation. Ginseng decreased chromatin decondensation in response to calcium ionophore and decreased AR in response to progesterone (P4) and ionophore. Conclusion: Zearalenol has adverse effects on sperm motility and function by targeting multiple signaling cascades, including P4, E2, and calcium pathways. Ginseng protects against chromatin damage and thus may be beneficial to reproductive fitness.
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Lepidium meyenii (maca) is a Peruvian plant of the Brassicaceae family cultivated for more than 2000 years, which grows exclusively in the central Andes between 4000 and 4500 m altitude. Maca is used as a food supplement and also for its medicinal properties described traditionally. Since the 90s of the XX century, an increasing interest in products from maca has been observed in many parts of the world. In the last decade, exportation of maca from Peru has increased from 1,415,000 USD in 2001 to USD 6,170,000 USD in 2010. Experimental scientific evidence showed that maca has nutritional, energizer, and fertility-enhancer properties, and it acts on sexual dysfunctions, osteoporosis, benign prostatic hyperplasia, memory and learning, and protects skin against ultraviolet radiation. Clinical trials showed efficacy of maca on sexual dysfunctions as well as increasing sperm count and motility. Maca is a plant with great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases.
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Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E(2), leukotriene B(4) and thromboxane B(2) were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the final treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200-300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their antidepressant activity as well as their positive effects on mental performance under stress.
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Adaptogens were initially defined as substances that enhance the “state of nonspecific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide.
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Ginseng root is used more often than other parts such as leaf stem although extracts from ginseng leaf-stem also contain similar active ingredients with pharmacological functions. Ginseng's leaf-stems are more readily available at a lower cost than its root. This article reviews the pharmacological effects of ginseng leaf-stem on some diseases and adverse effects due to excessive consumption. Ginseng leaf-stem extract contains numerous active ingredients, such as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract contains larger amounts of the same active ingredients than the root. These active ingredients produce multifaceted pharmacological effects on the central nervous system, as well as on the cardiovascular, reproductive and metabolic systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic, anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use, ginseng leaf-stem extract is quite safe; adverse effects occur only when it is over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have similar multifaceted pharmacological activities (for example central nervous and cardiovascular systems). In terms of costs and source availability, however, ginseng leaf-stem has advantages over its root. Further research will facilitate a wider use of ginseng leaf-stem.
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Panax ginseng occupies an important place among the tonic remedies of Oriental medicine. Pharmacological investigations show that crude ginsenosides can increase non-specific resistance of an organism to various untoward influences. The effects of purified derived derivatives have only recently become better studied in immunological and cell growth studies in animals and in man. This has now provided some evidence to suggest that ginseng is a drug that contains many derivatives with different pharmacological properties, which could be useful in clinical medicine.
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Intraperitoneal injection of Panax ginseng C. A. Mey tincture, Polyscias filicifolia Bailey tincture, Panax ginseng tincture or Eleutherococcus Maxim extract to rats produced a rise in plasma corticosterone 1 hour after the treatment. Immobilization-induced rise in plasma corticosterone was increased by 7-day pretreatment with any agent. Thus, the adaptation effect of Panax ginseng C. A. Mey and Polyscias filicifolia Bailey is probably realized through the pituitary-adrenocortical system.
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We investigated spermatogenic damage induced by anti-cancer agents in previous studies. The results showed that the damage to spermatogenesis induced by anti-cancer agents could be due to not only direct damaging effects on DNA synthesis but also a direct effect on Sertoli cell function. Thus, stimulating Sertoli cell function could protect against the damaging effects of anti-cancer agents on spermatogenesis, or stimulate recovery from impair spermatogenesis. We experimented with rats injected with the anti-cancer agents cis-diamminedichloroplatinum (CDDP) and adriamycin, which impair spermatogenesis, in order to examine this hypothesis. Follicle-stimulating hormone (FSH), which should stimulate Sertoli cell function in vivo, was selected, and the effects of FSH in protecting against damage or stimulating recovery from damage were investigated. The injection of FSH resulted in no significant differences in the histopathological findings of spermatogenic damage induced by anti-cancer agents or testicular transferrin concentration as compared to those observed without FSH injection. But, in the protocol of the experiments on acceleration of recovery from spermatogenic damage induced by anti-cancer agents, the spermatid index without FSH was 1.02±0.24, that with FHS 75IU/kg was 1.50±0.15, and that with FSH 150IU/kg was 1.62±0.39, a significant difference (p<0.05). Also, the PCNA labeling index and testicular transferrin concentration were significantly different with FSH from those without FSH.
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Herbs and related products are commonly used by patients who also seek conventional health care. All physicians, regardless of specialty or interest, care for patients who use products that are neither prescribed nor recommended. Some herbs have been extensively studied, but little is known about others. When a patient asks for advice regarding the use of a particular herb, how should a physician respond? Similarly, how does a physician determine if a patient's symptoms are caused by a "remedy"? This review attempts to answer these questions by investigating pertinent definitions, the history of herbs in medicine, epidemiology and prevalence of herbal use, and relevant psychosocial issues.
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Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential.
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The adaptogen concept is examined from an historical, biological, chemical, pharmacological and medical perspective using a wide variety of primary and secondary literature. The definition of an adaptogen first proposed by Soviet scientists in the late 1950s, namely that an adaptogen is any substance that exerts effects on both sick and healthy individuals by 'correcting' any dysfunction(s) without producing unwanted side effects, was used as a point of departure. We attempted to identify critically what an adaptogen supposedly does and to determine whether the word embodies in and of itself any concept(s) acceptable to western conventional (allopathic) medicine. Special attention was paid to the reported pharmacological effects of the 'adaptogen-containing plant' Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae), referred to by some as 'Siberian ginseng', and to its secondary chemical composition. We conclude that so far as specific pharmacological activities are concerned there are a number of valid arguments for equating the action of so-called adaptogens with those of medicinal agents that have activities as anti-oxidants, and/or anti-cancerogenic, immunomodulatory and hypocholesteroletic as well as hypoglycemic and choleretic action. However, 'adaptogens' and 'anti-oxidants' etc. also show significant dissimilarities and these are discussed. Significantly, the classical definition of an adaptogen has much in common with views currently being invoked to describe and explain the 'placebo effect'. Nevertheless, the chemistry of the secondary compounds of Eleutherococcus isolated thus far and their pharmacological effects support our hypothesis that the reported beneficial effects of adaptogens derive from their capacity to exert protective and/or inhibitory action against free radicals. An inventory of the secondary substances contained in Eleutherococcus discloses a potential for a wide range of activities reported from work on cultured cell lines, small laboratory animals and human subjects. Much of the cited work (although not all) has been published in peer-reviewed journals. Six compounds show various levels of activity as anti-oxidants, four show anti-cancer action, three show hypocholesterolemic activity, two show immunostimulatory effects, one has choleretic activity and one has the ability to decrease/moderate insulin levels, one has activity as a radioprotectant, one shows anti-inflammatory and anti-pyretic activities and yet another has shown activity as an antibacterial agent. Some of the compounds show more than one pharmacological effect and some show similar effects although they belong to different chemical classes. Clearly, Eleutherococcus contains pharmacologically active compounds but one wishes that the term adaptogen could be dropped from the literature because it is vague and conveys no insights into the mechanism(s) of action. If a precise action can be attributed to it, then the exact term for said action should obviously be used; if not, we strongly urge that generalities be avoided. Also, comparison of Eleutherococcus with the more familiar Panax ginseng C.A. Meyer (Araliaceae), 'true ginseng' has underscored that they differ considerably chemically and pharmacologically and cannot be justifiably considered as mutually interchangeable. Accordingly, we recommend that the designation 'Siberian ginseng' be dropped and be replaced with 'Eleutherococcus'. In the case of both Eleutherococcus and true ginseng, problems inherent in herbal preparation use include inconsistencies not only in terms of indications for use, but in the nomenclature of constituent chemical compounds, standardization, dosage and product labeling. (ABSTRACT TRUNCATED)
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Rhodiola rosea is a popular plant in traditional medical systems in Eastern Europe and Asian with a reputation for stimulating the nervous system, decreasing depression, enhancing work performance, eliminating fatigue, and preventing high altitude sickness. Rhodiola rosea has been categorized as an adaptogen by Russian researchers due to its observed ability to increase resistance to a variety of chemical, biological, and physical stressors. Its claimed benefits include antidepressant, anticancer, cardioprotective, and central nervous system enhancement. Research also indicates great utility in asthenic conditions (decline in work performance, sleep difficulties, poor appetite, irritability, hypertension, headaches, and fatigue) developing subsequent to intense physical or intellectual strain. The adaptogenic, cardiopulmonary protective, and central nervous system activities of Rhodiola rosea have been attributed primarily to its ability to influence levels and activity of monoamines and opioid peptides such as beta-endorphins.
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To further assess the effect of Panax ginseng on survival and sperm quality of guinea pigs exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Eighty male guinea pigs were divided into eight equal groups. The normal control (NC) group received vehicle and saline; one dose of 1 micro g/kg body weight TCDD was injected intraperitoneally into the single TCDD-treated (TT) and test groups (P100, P200, C100, C200); G and NC groups received vehicle instead of TCDD. P. ginseng water extract (PG-WE) was injected intraperitoneally at daily doses of 100 (G100, P100, C100) or 200 mg/kg body weight (G200, P200, C200). The PG-WE was administered to the P and G groups for 12 weeks from 1 week before TCDD exposure, and to the C groups for 10 weeks from 1 week after TCDD exposure. After a 4-week discontinuation of PG-WE treatment after the 13th week the surviving males were then tested for fertility by mating them with females. The litter size, death rate, male/female birth ratio and physical abnormalities of the progeny were investigated. After confirming delivery of the offspring, the parent males were killed at 40 weeks, their testes weighed and sperm quality assessed. All TT animals died within 18 days after TCDD exposure, but 40-70% of the PG-WE-treated groups, depending on the group, survived until death at 40 weeks. All the surviving males were fertile regardless of TCDD exposure; there was no difference in litter size between the NC and test groups. Notably the death rate of progeny born to PG-WE-treated groups was lower than that of progeny born to the NC group. The progeny born to TCDD-exposed groups (P200 and C groups) had a preponderance of females. G Group animals had higher sperm quality than that of NCs even long after discontinuing PG-WE. P. ginseng improves the survival rate and sperm quality in guinea pigs exposed to TCDD.