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Evidence-Based Efficacy of Adaptogens in Fatigue, and Molecular Mechanisms Related to their Stress-Protective Activity
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The aim of this review article is to assess the level of scientific evidence presented by clinical trials of adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong scientific evidence is available for Rhodiola rosea SHR-5 extract, which improved attention, cognitive function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness. Based on their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal preparations that increase tolerance to mental exhaustion and enhance attention and mental endurance in situations of decreased performance. The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stress-activated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their up-regulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly, increased longevity.
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... In 2011, the ethanolic extract (67-70 %) of roots and rhizomes of R. rosea was monographed by the HMPC as a traditional herbal medicinal product "for temporary relief of symptoms of stress, such as fatigue and sensation of weakness" (EMA/HMPC/232091/2011). During the past decades, the pharmacological activities of this plant extract have been investigated intensively [3,11,12]. Secondary metabolites from different compound classes, namely, phenylethanoids, phenylpropanoids, monoterpenoids, cyanogenic compounds, flavonoids, proanthocyanidines, and tannins, are described as roseroot constituents [3]. In 1970, salidroside (3), belonging to the structure class of phenylpropanoids, was believed to be the main active principle in R. rosea extracts and was therefore closely investigated, not only for adaptogenic effects [3,13] but also for antiviral activities, i.e., inhibition of dengue virus via inhibiting viral protein synthesis and boosting host immunity [8] and anti-coxsackie virus B3 activity to treat viral myocarditis in vitro and in vivo [9]. ...
... All isolated flavonoids and their glycosides showed pronounced anti-H3N2 influenza virus A/Hong Kong/68 potential. With SIs above 6.5, tricin (12) and its glycoside (7) exerted similar IC 50 values of 13 µM and 15 µM, respectively. The most active roseroot metabolite was rhodiosin (10), a monodesmosidic glycosylated disaccharide of herbacetin (▶ Fig. 1), with an IC 50 value of 7.9 µM and an SI of > 13 (▶ Table 4 and Fig. 3S, Supporting Information). ...
... In the present study, the standardized hydroethanolic extract exhibited distinct and specific anti-influenza virus activity. This was mainly observed for one particular compound class, i.e., the flavonoids rhodiosin (10), tricin (12), and tricin-5-O-β-D-glu-▶ Fig. 1 Chemical structures of the 12 compounds isolated from R. rosea extract. copyranoside (7). ...
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... The ideal adaptogen should reduce negative changes caused by stress, be safe and act beneficially even when the dose given is higher than required, and be free of adverse side effects, such as not affecting the functioning of the body more than needed [120]. Based on the above-mentioned characteristics, Ashwagandha can be considered as an adaptogen. ...
In recent years, there has been a significant surge in reports on the health-promoting benefits of winter cherry (Withania somnifera), also known as Ashwagandha. Its current research covers many aspects of human health, including neuroprotective, sedative and adaptogenic effects and effects on sleep. There are also reports of anti-inflammatory, antimicrobial, cardioprotective and anti-diabetic properties. Furthermore, there are reports of reproductive outcomes and tarcicidal hormone action. This growing body of research on Ashwagandha highlights its potential as a valuable natural remedy for many health concerns. This narrative review delves into the most recent findings and provides a comprehensive overview of the current understanding of ashwagandha’s potential uses and any known safety concerns and contraindications.
... Several authors provide supporting material in favor of the anabolic action of adaptogens from the ginseng family [30], [31], [32], [33]. Also, doubts are expressed about the presence of similar properties in herbal preparations [34], [35]. ...
Adverse environmental factors, stress, lack of sleep and rest, and heavy physical exertion, deplete the human body. In particular, the reserves of the main metabolites, water, and oxygen, are very limited. People, especially athletes, need to take special dietary supplements with adaptogenic properties to adapt to stressful extreme loads. In this study, the influence of using extracts of leuzea, ginseng, and Eleutherococcus on athletes' performance, endurance, strength, and emotional state is carried out. The studies were conducted on four groups of male athletes aged from 19 to 25 years. For three weeks, diagnostics of vital lung capacity, Stange, and Genchi tests are carried out, and data on the general impressions of athletes are collected. According to the research results, the use of adaptogens leads to an increase in physical performance. After the first week of the study, a positive effect on the human body are noticed: improve well-being and increased athletic performance. When using Eleutherococcus, there was a change in the work of the central nervous system (motor functions): tasks begin to be performed in an organized and accelerated manner without deterioration of well-being, but the volume of strength exercises remained the same. When using the drug leuzea, muscle strength was noted, which allowed to increase the load. There is a positive effect of phytopreparations on the body, namely on the functions of the cardiovascular, central nervous and endocrine systems. In 4 participants who took leuzea, the performance in power competitions improved by 18.5% compared to the control group. The intake of Eleutherococcus and ginseng is accompanied by an increase in the activity of neurotransmitter cells, i.e., the effect on the mesolimbic system. In addition, a study of hematological blood parameters and hormonal statuses at the beginning and end of the study was conducted with the subjects who took leuzea extract. So, the use of the drug leuzea leads to the following positive changes: a more significant increase in ESR, a more significant increase in hemoglobin, compared with the control group. The conclusion is made about the practicality of taking biologically active additives based on some plant adaptogens.
... A recent definition of an adaptogen is, "a class of metabolic regulators, which increase the ability of an organism to adapt to environmental factors and avoid damage from such factors". 3 parts of the plant used therapeutically. Leaves are simple, ovoid, hairless or smooth, those in the floral region smaller and opposite; flowers are inconspicuous, greenish or luridyellow, in axillary, umbellate chymes; berries are small, globose, orange-red when mature, enclosed in the persistent calyx; seeds yellow, reniform. ...
is a valuable medicinal plant in the Solanaceae family. It is commonly known as Indian ginseng, Winter Cherry and is widely distributed around the globe. The plant is used traditional for its ameliorative properties against a human medical condition like cancer, diabetes, asthma, hypertension, stress, etc. Stress is a state of mental or emotional strain or tension, which can lead to underperformance and adverse clinical changes. is considered a potent adaptogen and anti-stress agent that could have some potential to improve physical and mental condition of a person. This review mainly focuses on anti-stress property of .
... On the other hand, adaptogens are herbal solution for reducing stress and normalizing body's responses to cope with it (Provino, 2010;Salve et al., 2019). Ashwagandha (the botanical name is Withania somnifera Dunal) is a conventional Ayurvedic herb used for stress and anxiety treatment (Alramadhan et al., 2012;Panossian & Wikman, 2009;Provino, 2010). Ashwagandha has antiinflammatory, antioxidant, antitumor, hypotensive, immunomodulatory, and anxiolytic properties (Oliveira & Leitão, 2016;Singh, Sharma, Dudhe, & Singh, 2010). ...
Clinical trial studies revealed conflicting results on the effect of Ashwagandha extract on anxiety and stress. Therefore, we aimed to evaluate the effect of Ashwagandha supplementation on anxiety as well as stress. A systematic search was performed in PubMed/Medline, Scopus, and Google Scholar from inception until December 2021. We included randomized clinical trials (RCTs) that investigate the effect of Ashwagandha extract on anxiety and stress. The overall effect size was pooled by random‐effects model and the standardized mean difference (SMD) and 95% confidence interval (CIs) for outcomes were applied. Overall, 12 eligible papers with a total sample size of 1,002 participants and age range between 25 and 48 years were included in the current systematic review and meta‐analysis. We found that Ashwagandha supplementation significantly reduced anxiety (SMD: −1.55, 95% CI: −2.37, −0.74; p = .005; I2 = 93.8%) and stress level (SMD: −1.75; 95% CI: −2.29, −1.22; p = .005; I2 = 83.1%) compared to the placebo. Additionally, the non‐linear dose–response analysis indicated a favorable effect of Ashwagandha supplementation on anxiety until 12,000 mg/d and stress at dose of 300–600 mg/d. Finally, we identified that the certainty of the evidence was low for both outcomes. The current systematic review and dose–response meta‐analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high‐quality studies are needed to firmly establish the clinical efficacy of the plant.
Roślinne adaptogeny wykazują wiele efektów farmakologicznych w organizme ludzkim, charakteryzując się jednocześnie dużym bezpieczeństwem stosowania. Liczne substancje roślinne, obdarzone właściwościami adaptogennymi, wywodzą się z Tradycyjnej Medycyny Chińskiej (TCM). Część z nich znalazła również zastosowanie w konwencjonalnej medycynie zachodniej. Celem niniejszej publikacji jest przybliżenie potencjału terapeutycznego trzech gatunków roślin z rodzaju Scutellaria L. (tarczyca), charakteryzujących się aktywnością adaptogenną. Tarczyce: bajkalska (Scutellaria baicalensis Georgi.) oraz brodata (Scutellaria barbata D.Don.) to dwa gatunki azjatyckie wykorzystywane w TCM, natomiast tarczyca bocznokwiatowa (Scutellaria lateriflora L.) jest taksonem rodzimym flory Ameryki Północnej, stosowanym pierwotnie w medycynie ludowej Indian. Głównymi składnikami tarczyc, którym przypisuje się właściwości adaptogenne są składniki polifenolowe z grupy flawonów (głównie: bajkaleina, bajkalina, wogonina). Wyciągi z tarczyc, bogate w te związki, stanowią środki lecznicze o silnym działaniu przeciwzapalnym, wykazujące szeroką aktywność antybiodegeneracyjną (neuro- hepato- i kardioprotekcyjną) oraz przeciwnowotworową. Ponadto, jako adaptogeny, flawony tarczyc wykazują normalizujący wpływ na OUN, łagodząc dolegliwości natury psychicznej, w tym reakcje lękowe, stany napięcia nerwowego czy zaburzenia snu.
Panax ginseng is a precious and ancient medicinal plant. The completion of its genome sequencing has laid the foundation for the study of proteome and peptidome. However, the high abundance of secondary metabolites in ginseng reduces the identification efficiency of proteins and peptides in mass spectrometry. In this report, strong cation exchange pretreatment was carried out to eliminate the interference of impurities. Based on the charge separation of proteolytic peptides and metabolites, the sensitivity of mass spectrometry detection was greatly improved. After pretreatment, 2322 and 2685 proteins were identified from the root and stem leaf extract. Further, the ginseng peptidome was analyzed based on this optimized strategy, where 970 and 653 endogenous peptides were identified from root and stem leaf extract, respectively. Functional analysis of proteins and endogenous peptides provided valuable information on the biological activities, metabolic processes, and ginsenoside biosynthesis pathways of ginseng.
Актуальным вопросом для специалистов самых разных клинических дисциплин является совершенствование подходов к диагностике и лечению широкого круга заболеваний, в патогенезе которых большую роль играет рассогласованность циклических процессов, управляемых внутренними и внешними ритмогенными детерминантами. Цель лекции - представление накопленных к настоящему времени знаний о физиологии и патофизиологии биоритмов, причинах и последствиях десинхронозов.
An urgent challenge for various clinical specialists is improving approaches to the diagnosis and treatment of multiple diseases, which pathogenesis includes a mismatch of cyclic processes controlled by internal and external rhythmogenic determinants. The purpose of this lecture was to present the current knowledge about physiology and pathophysiology of biorhythms as well as and about the causes and consequences of desynchronosis.
Purpose of review This review summarizes and highlights recent advances in current knowledge of the relationship between coffee and caffeine consumption and risk of coronary heart disease. Potential mechanisms and genetic modifiers of this relationship are also discussed. Recent findings Studies examining the association between coffee consumption and coronary heart disease have been inconclusive. Coffee is a complex mixture of compounds that may have either beneficial or harmful effects on the cardiovascular system. Randomized controlled trials have confirmed the cholesterol-raising effect of diterpenes present in boiled coffee, which may contribute to the risk of coronary heart disease associated with unfiltered coffee consumption. A recent study examining the relationship between coffee and risk of myocardial infarction incorporated a genetic polymorphism associated with a slower rate of caffeine metabolism and provides strong evidence that caffeine also affects risk of coronary heart disease. Several studies have reported a protective effect of moderate coffee consumption, which suggests that coffee contains other compounds that may be beneficial. Summary Diterpenes present in unfiltered coffee and caffeine each appear to increase risk of coronary heart disease. A lower risk of coronary heart disease among moderate coffee drinkers might be due to antioxidants found in coffee.
It has been found empirically that some plants, such as Eleutherococcus senticosus, Rhodiola rosea, Schizandra chinensis and Bryonia alba etc, used in traditional medicine to increase stamina and general well-being, also increase the state of non-specific resistance in stress. These plants have been named adaptogens and are defined as metabolic regulators that reduce the damaging effects of various stressors by virtue of a reduction of the reactivity of the host defence system. Adaptogens increase the ability of the organism to cope with stress, thus implying a curative effect on stress- induced disorders. Such drugs are often classified as preparations which stimulate the central nervous system (CNS) in manuals and handbooks on pharmacology. However, adaptogens differ in significant ways from classical CNS-stimulants. Experiments on frogs show that adaptogens do not have direct anti-narcotic effects on the CNS unlike other stimulants such as phenamine, caffeine etc. The mechanisms of action of adaptogens are related to the regulation of the stress system - neuroendocrine - immune complex, and are associated with the biochemical adaptation of cells and organisms to stress. A large number of uncontrolled as well as placebo-controlled, randomised, double-blind clinical studies have shown that standardised extracts of E. senticosus, R. rosea and S. chinensis are efficient at increasing mental and physical work capacity in situations of fatigue and stress, as well as in the treatment of some psychiatric disorders such as neurosis, psychogenic depression, astheno-depressive states, alcoholism etc. Comparing the concept of quality of life with the concept of adaptogens, it is suggested that that this group of botanicals could be useful in improving the quality of life in many categories of patients and even in healthy subjects.
Heat Shock Proteins: Potent Mediators of Inflammation and Immunity currently provides the most up-to-date review on new mechanisms and provides exciting insights into how heat shock proteins modulates the hosts immune response. Written by leaders in the field of heat shock protein immunobiology, the chapters systematically and in a step wise fashion takes the reader through the fascinating sequence of events by which heat shock proteins activate immune responses and provides answers as to its biological significance to the host. From the early stages of binding and receptors-mediated signalling, to new paradigms by which heat shock proteins are released into the circulation, to antigen processing and presentation, and finally to the immune response itself this book is a must read for graduate and postgraduates in the field of Biology (plant and mammal), Biochemistry (pro- and eukaryotic), Immunology, Microbiology, Exercise Medicine, Physiology, Inflammatory diseases, Autoimmunity, Pharmacology and Pathology.
Though caffeine has been one of the most widely used psychoactive substances throughout history, it has been difficult to work out molecular mechanisms that account for its behavioral actions. One of the first widely considered mechanisms relates to cyclic AMP. Soon after the identification of phosphodiesterase as an enzyme degrading cyclic AMP, Sutherland and associates (Sutherland and Rall 1958; Butcher and Sutherland 1962) showed that xanthines, including caffeine and theophylline, inhibit phosphodiesterase. By inhibiting this enzyme xanthines might elevate levels of cyclic AMP. However, substantial inhibition of phosphodiesterase requires millimolar concentrations of caffeine, roughly 100 times the caffeine levels in the brain after ingestion of typical doses in man. Further, some inhibitors of phosphodiesterase that are 100–1000 times more potent than caffeine lack behavioral effects.
