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Rhodiola rosea in stress induced fatigue - A double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty

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Abstract

The aim of this study was to investigate the effect of repeated low-dose treatment with a standardized extract SHR/5 of rhizome Rhodiola rosea L, (RRE) on fatigue during night duty among a group of 56 young, healthy physicians. The effect was measured as total mental performance calculated as Fatigue Index. The tests chosen reflect an overall level of mental fatigue, involving complex perceptive and cognitive cerebral functions, such as associative thinking, short-term memory, calculation and ability of concentration, and speed of audio-visual perception. These parameters were tested before and after night duty during three periods of two weeks each: a) a test period of one RRE/placebo tablet daily, b) a washout period and c) a third period of one placebo/RRE tablet daily, in a double-blind cross-over trial. The perceptive and cognitive cerebral functions mentioned above were investigated using 5 different tests. A statistically significant improvement in these tests was observed in the treatment group (RRE) during the first two weeks period. No side-effects were reported for either treatment noted. These results suggest that RRE can reduce general fatigue under certain stressful conditions.

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... addition, various differently standardized herbal preparations of the same medicinal plant may have different pharmacokinetic and pharmacodynamic dose-effect responses. For example, the maximal active antifatigue, antidepressant, and antistressor dose of the SHR-5 brand of R. rosea extract[355][356][357]360 might be inactive for a different extract of R. rosea despite the fact that both products are extracted from Rhodiola roots that have different chemical compositions.350,582 Finally, we acknowledge the difficulties in producing herbal medicinal products that provide reproducible effectiveness over time, and this represents a serious challenge and limitation of herbal medicinal products and dietary supplements in general. ...
... ,14,15,26,27,48,74,75,216,275,350,[353][354][355][356][357][358][359][360][361][362][363][364][365][366][367] In a number of clinical studies, the beneficial effects of adaptogens have been demonstrated on healthy subjects in stress conditions.26,27,48,74,75,324,353,356,357,359,362 This is especially true of the mental and physical performance of fatigue and mental strain. ...
... ,14,15,26,27,48,74,75,216,275,350,[353][354][355][356][357][358][359][360][361][362][363][364][365][366][367] In a number of clinical studies, the beneficial effects of adaptogens have been demonstrated on healthy subjects in stress conditions.26,27,48,74,75,324,353,356,357,359,362 This is especially true of the mental and physical performance of fatigue and mental strain. ...
Article
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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.
... R. rosea is dioecian and perennial plant having separate male and female plants. Rhodiola genus have originated in the mountainous regions of Himalayas and Southwest China (Darbinyan et al. 2000). There are about 90 species of Rhodiola reported in different regions of the world and 73 species are found in China (Booker et al. 2016). ...
... The cell cultures of Rhodiola rosea on animals and humans have shown antifatigue, antistress, anticancer, immune-enhancing and sexual-stimulating effects (Darbinyan et al. 2000). ...
Chapter
Sickle cell anemia (SCA) is an inherited disorder in the β-globin chain of hemoglobin that affects millions of people around the world, especially children. This disease prevalently occurs in some Mediterranean and Saharan Africa. For the treatment of SCA patients, a wide range of drugs have been explored by targeting antisickling activity, γ-globulin induction, antiplatelet effect, etc., but hardly a few drugs have shown potential to combat with this complex disease phenomenon. In spite of unprecedented advances in modern system of medicine, people in the disease-prone area have been taking traditional medicinal plants or plant-derived products to increase the life span of patients. Moreover, numerous clinical trials have been going on for the use of natural products under the purview of symptomatic management of SCA. This chapter is focused on the effect of natural products in pure form or characterized phytoconstituents on particularly inhibition of hemoglobin polymerization. This summarized information will be beneficial for further exploration of new therapeutics in the treatment arena of SCA.
... R. rosea is dioecian and perennial plant having separate male and female plants. Rhodiola genus have originated in the mountainous regions of Himalayas and Southwest China (Darbinyan et al. 2000). There are about 90 species of Rhodiola reported in different regions of the world and 73 species are found in China (Booker et al. 2016). ...
... The cell cultures of Rhodiola rosea on animals and humans have shown antifatigue, antistress, anticancer, immune-enhancing and sexual-stimulating effects (Darbinyan et al. 2000). ...
... 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]. ...
... A fast orthogonal chromatographic step enabled the purification of 12 secondary metabolites from the R. rosea extract. The applicability of this method for a broad and structurally diverse spectrum of compounds of a wide polarity range is further represented by obtaining a cyanogenic compound (3) and two monoterpenoids (8,11) as well as minor flavonoid glycosides (7, 10) and the methoxylated flavonoid 12. ...
Article
In a cytopathic effect inhibition assay, a standardized Rhodiola rosea root and rhizome extract, also known as roseroot extract (SHR-5), exerted distinct anti-influenza A virus activity against HK/68 (H3N2) (IC50 of 2.8 µg/mL) without being cytotoxic. For fast and efficient isolation and identification of the extractʼs bioactive constituents, a high-performance countercurrent chromatographic separation method was developed. It resulted in a three-stage gradient elution program using a mobile phase solvent system composed of ethyl acetate/n-butanol/water (1 : 4 : 5 → 2 : 3 : 5 → 3 : 2 : 5) in the reversed-phase mode. The elaborated high-performance countercurrent chromatographic method allowed for fractionation of the complex roseroot extract in a single chromatographic step in a way that only one additional orthogonal isolation/purification step per fraction yielded 12 isolated constituents. They cover a broad polarity range and belong to different structural classes, namely, the phenylethanoid tyrosol and its glucoside salidroside, the cinnamyl alcohol glycosides rosavin, rosarin, and rosin as well as gallic acid, the cyanogenic glucoside lotaustralin, the monoterpene glucosides rosiridin and kenposide A, and the flavonoids tricin, tricin-5-O-β-D-glucopyranoside, and rhodiosin. The most promising anti-influenza activities were determined for rhodiosin, tricin, and tricin-5-O-β-D-glucopyranoside with IC50 values of 7.9, 13, and 15 µM, respectively. The herein established high-performance countercurrent chromatographic protocol enables fast and scalable access to major as well as minor roseroot constituents. This is of particular relevance for extract standardization, quality control, and further in-depth pharmacological investigations of the metabolites of this popular traditional herbal remedy.
... The antiasthenic effects of R. rosea were evaluated by a randomized double-blind cross-over trial on a group of 56 young, healthy physicians during night duty [158]. The effects were measured as total mental performance calculated as Fatigue Index and through different perceptive and cognitive tests which were performed before and after night duty. ...
... The effects were measured as total mental performance calculated as Fatigue Index and through different perceptive and cognitive tests which were performed before and after night duty. In the R. rosea treatment group, significant improvements were observed in all the tests during the first two weeks' period, and no side-effects were reported [158]. ...
Article
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Recent studies focused on the pharmacology and feasibility of herbal compounds as a potential strategy to target a variety of human diseases ranging from metabolic to brain disorders. Accordingly, bioactive ingredients which are found within a variety of herbal compounds are reported to produce both neuroprotective and psychotropic activities which may help to combat mental disorders such as depression, anxiety, sleep disturbances and cognitive alterations. In the present manuscript, we focus on three herbs which appear effective in mitigating anxiety or depression with favourable risk-benefit profiles, namely Scutellaria baicalensis (S. baicalensis), Hericium erinaceus (H. erinaceus) and Rhodiola rosea (R. rosea). These three traditional folk medicinal herbs target the main biochemical events that are implicated in mental disorders, mimicking, to some extent, the mechanisms of action of conventional antidepressants and mood stabilizers with a wide margin of tolerability. In detail, they rescue alterations in neurotransmitter and neuro-endocrine systems, stimulate neurogenesis and the synthesis of neurotrophic factors, and they counteract oxidative stress, mitochondrial dysfunction and inflammation. Albeit the encouraging results that emerge from both experimental and clinical evidence, further studies are needed to confirm and better understand the mental-health promoting, and specifically, the antidepressant effects of these herbs.
... In recent years, the research on arctic root has mainly concerned chemical and biological profiling as well as pharmacological activity. Various biological activities of arctic root, including antioxidant, antibacterial, antiviral, anticancer, immunostimulant, antidepressant, and ergogenic, were identified [3][4][5][6]. In clinical practice, arctic root has been investigated to improve physical and mental performance and treat fatigue and depression. ...
Article
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Artic root is a well-known plant adaptogen with multipotential pharmacological properties. Thin-layer chromatography (TLC)—screening followed by diode-array high-performance liquid chromatography and nuclear magnetic resonance spectroscopy proved to be a reliable and convenient method for the simultaneous determination of the quality of various herbal raw materials and supplements. This combination allowed for comparing and differentiating arctic root samples as well as defining their authenticity. The study provided information on the chemical and biological properties of the seven chosen samples as well as qualitative and quantitative evaluation of the quality markers: rosavin, salidroside, and p-tyrosol. The absence of rosavin, salidroside, and p-tyrosol in three samples was detected using TLC screening and confirmed by HPLC-DAD and NMR. The paper highlighted the importance of quality control and strict regulation for herbal medicine supplements and preparations.
... In recent years, the research on arctic root has mainly concerned chemical and biological profiling as well as pharmacological activity. Various biological activities of arctic root, including antioxidant, antibacterial, antiviral, anticancer, immunostimulant, antidepressant, and ergogenic, were identified [3][4][5][6]. In clinical practice, arctic root has been investigated to improve physical and mental performance and treat fatigue and depression. ...
Preprint
Artic root is a well-known plant adaptogen with multipotential pharmacological properties. Thin-layer chromatography (TLC) – screening followed by diode-array high-performance liquid chromatography and nuclear magnetic resonance spectroscopy proved to be a reliable and convenient method for simultaneous determination of quality of various herbal raw materials and supplements. This combination allowed for comparing and differentiating arctic root samples as well as defining their authenticity. The study provided information on the chemical and biological properties of the seven chosen samples as well as qualitative and quantitative evaluation of the quality markers: rosavin, salidroside, and p-tyrosol. The absence of rosavin, salidroside, and p-tyrosol in three samples was detected using TLC-screening and confirmed by HPLC-DAD and NMR. The paper highlighted the importance of quality control and strict regulation for herbal medicine supplements and preparations.
... Salidroside is a glycoside extracted from Rhodiola rosea plant (Qu et al., 2012;Son et al., 2009;Darbinyan et al., 2000;Shevtsov et al., 2003). A study revealed that salidroside inhibits ERS by downregulating GRP78, p-PERK, and p-IRE1, demonstrating its neuroprotective effect in the 6-OHDA-treated DA neuronal cell line (SN4741) (Tao et al., 2016). ...
Article
The primary aim of this review is to summarize the literature on natural products that are effective in the treatment of various neurological disorders by targeting endoplasmic reticulum stress (ERS). Various electronic databases such as SCOPUS, PubMed, Web of Science, and Google Scholar were searched for relevant publications. ERS has been implicated in the pathogenesis of numerous neurological disorders such as cerebral ischemia, Parkinson's disease, Alzheimer's disease, and Huntington’s disease. Several natural products targeting ERS signalling pathways provide therapeutic options for neurological diseases, and in this review, the potential neuroprotective properties of these products are discussed.
... Darbinyan et al. [10] investigated the effect of the chronic administration of 170 mg of standardized R. rosea rhizome extract on aspects of mental performance and fatigue on 56 healthy male and female physicians (age 24-35) on night duty for 14 days. In a randomized, placebo-controlled, double-blind, cross-over study with a wash-out period, total mental performance was measured by calculating a Fatigue Index that reflected on the outcomes of complex perceptive and cognitive cerebral functions, such as associative thinking, attention capacity, speed of visual and auditory perception and short-term memory. ...
Article
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Rhodiola rosea L. has a long history of use in traditional medicine to stimulate the nervous system, treat stress-induced fatigue and depression, enhance physical performance and work productivity and treat gastrointestinal ailments and impotence. Apart from its well-established traditional use, a significant number of publications on the clinical efficacy of various R. rosea preparations can be found in the literature. The majority of these studies are related to the efficacy of R. rosea in terms of cognitive functions and mental performance, including various symptoms of life-stress, fatigue and burnout. The beneficial effects of this medicinal plant on enhancing physical performance have also been evaluated in professional athletes and non-trained individuals. Moreover, even though most evidence originates from pre-clinical trials, several clinical studies have additionally demonstrated the remediating effects of R. rosea on cardiovascular and reproductive health by addressing non-specific stress damage and reversing or healing the disrupted physiologies and disfunctions. Overall, in accordance with its aim, the results presented in this review provide an encouraging basis for the clinical efficacy of R. rosea preparations in managing various aspects of stress-induced conditions.
... Sal, a principal physiologically active constituent from Rhodiola genus herb drug which has been widely verified to be no toxicity or less side effects in a multitude of animal experiments and clinical trials [161], is recognized as a safe natural ingredient agent similarly. The results of pharmacokinetic studies showed that Sal was widely distributed into multiple tissues and organs after entering circulation system, and can still converge in brain spite of keeping a low-rise concentration [162]. ...
Article
Ischemic stroke is an acute cerebrovascular disease and the third most common cause of death after ischemic heart disease. Increasing attention is being paid to finding effective treatments through traditional medicine. Thus, studying the traditional medicine for the treatment of ischemic stroke is of great importance. Traditional medicine in China includes traditional Chinese medicine (TCM) and other ethnic medicines, which is rich in variety and resources. This review first introduces the treatment mechanisms associated with ischemic stroke, such as antioxidant nitrification, antiexcitotoxic, antiapoptotic, anti-inflammatory, antiplatelet and anticoagulation mechanisms. Then, we calculated the frequency of prescription use for ischemic stroke and summarized the treatments for ischemic stroke by investigating 13 drug monographs and standards. We found 192 prescriptions from the traditional medical system for ischemic stroke, including Angong Niuhuang pill, Qishiwei Zhenzhu Pills, Ginkgo biloba leaf, and other traditional Chinese patent medicines and national medicines. There were 398 kinds of traditional medicine, including 301 kinds of plant-based medicines, 54 kinds of animal-based medicines, 28 kinds of mineral-based medicines, and 15 kinds of other medicines. We introduced the names, families, medicinal components, traditional uses, phytochemical information, and pharmacological activities of the commonly used Chinese patent medicines and TCMs. In addition, some chemicals were introduced. These medicines may be potential candidates for the treatment of ischemic stroke. This work provides a reference for the research and clinical use of new drugs for ischemic stroke.
... In weiteren Studien konnte zudem gezeigt werden, dass Rhodiola rosea den Sauerstoffverbrauch des Herzens signifikant verringert und auch als Antioxidans die Zellen vor physikalischen und chemischen Noxen schützen kann [17,18,19,20,21]. Zudem konnte eine positive Wirkung auf Konzentrationsfähigkeit und Aufmerksamkeit aufgezeigt werden [22,23,24] sowie auf die körperliche Leistungsfähigkeit und Ausdauer [25,26,27,28]. Bei Patienten mit chronisch obstruktiver Lungenerkrankung wurde eine antiinflammatorische Wirkung von Rosenwurzpräparaten gezeigt [29,30]. ...
Article
Zusammenfassung Hintergrund Pflanzliche Arzneimittel finden in Deutschland traditionell sehr häufig Anwendung. Ihre Nutzung beruht auf einem jahrhundertelangen Erfahrungsschatz. Historische Quellen werden jedoch bei der wissenschaftlichen Untersuchung pflanzlicher Arzneimittel häufig außer Acht gelassen. Das Ziel der vorliegenden narrativen Übersichtsarbeit ist es, am Beispiel der Arzneipflanze Rhodiola rosea (Rosenwurz) einen umfassenden Überblick über den integrierten Forschungsstand zu dieser Pflanze zu liefern. Hierfür wurde historische Literatur zur traditionellen Nutzung von R. rosea sowohl aus naturwissenschaftlicher als auch aus geschichtswissenschaftlicher Perspektive analysiert und in einer beschreibenden Zusammenfassung dargestellt. Zusammenfassung Insgesamt wurden 15 historische Quellen mit Informationen zur traditionellen Nutzung von Rosenwurz identifiziert. Die historische Quellenlage ist allerdings als sehr überschaubar einzuschätzen. Die erste Erfassung von R. rosea zur medizinischen Verwendung geht zurück auf Dioskurides in der Antike. Viele der zeitlich nachfolgenden Quellen beziehen sich bei ihrer Beschreibung von Rosenwurz direkt auf die Darstellungen des Dioskurides. Alle gefundenen Quellen zu Rosenwurz beschreiben eine Anwendung bei Kopfschmerzen. Darüber hinaus wird eine Anwendung bei Geschwülsten, Periodenbeschwerden, Leberleiden, „Wassersucht“, „Hysterie“ sowie eine nervenstärkende Wirkung beschrieben, welche sich durchaus in modernen Studienergebnissen wiederfinden lässt. Die heutige medizinische Nutzung von R. rosea als Adaptogen mit stressprotektiver Wirkung wird in der Form jedoch nicht in den historischen Quellen beschrieben. Im Gegensatz zur heutigen Anwendung in Form von Kapseln, Tabletten oder Tropfen erfolgte die traditionelle Anwendung hauptsächlich äußerlich in Form von Salben, Pasten oder Wickeln. Zu konkreten Anwendungsmodalitäten lassen sich nur wenige bis keine Informationen aus den vorliegenden Quellen gewinnen. Eine weiterführende systematische Recherche von historischen Quellen Nord- und Osteuropas stellt aufgrund des Vorkommens der Pflanze in überwiegend zirkumpolaren und alpinen Regionen möglicherweise eine wertvolle Ressource für zusätzliche Informationen dar. Kernaussage Historische Quellen zu traditionellen medizinischen Verfahren stellen eine wichtige Informationsquelle für die heutige Wissenschaft dar, welche dazu beitragen können, die heutige, gut etablierte medizinische Anwendung zu untermauern und darüber hinaus wertvolle Ansatzpunkte für neue Forschungsrichtungen bieten.
... In a placebo-controlled double-blind study, the effect of a daily low-dose regimen of 170 mg SHR-5 Rhodiola rosea extract (4.5 mg of salidroside) was tested versus placebo on the mental performance of healthy young physicians aged 24 to 35 (n=56) with nonspecific fatigue during night shifts [68]. Subjects were randomly assigned to group A (n=26) that received a daily dose of SHR-5 for 2 weeks or group B (n=30) that received a daily dose of placebo for 2 weeks. ...
Article
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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.
... The chronic mood and fatigue effects observed here may therefore be due to facilitation of acetylcholine neurotransmission. Indeed, caffeine [52] and other natural extracts [53,54] are known to promote benefits to mental fatigue, through inhibition of acetylcholine esterase [55]. With respect to cognition, RVIP was previously reported to be an acetylcholine-sensitive task following observed increases and decreases in task performance after treatment with an acetylcholine agonist (scopolamine) and an acetylcholine antagonist (nicotine), respectively [35]. ...
Article
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Purpose Cereboost®, an American ginseng extract, has shown improved short-term memory and attention/alertness in healthy young and middle-aged individuals, potentially via modulation of the gut microbiome and upregulation of neurotransmitters such as acetylcholine. Here, we explored the effects of Cereboost® on cognition and mood in the first 6 h post intervention (acute), after 2 weeks daily supplementation (chronic), and whether 2 weeks daily supplementation altered the response to a single acute dose (acute-on-chronic). A concurrent in vitro study evaluated effects of repeated Cereboost® administration on human gut microbiota. Methods Cognitive effects of Cereboost® were assessed using a double-blind, randomized, placebo-controlled clinical trial, with 61 healthy young adults. Modulation of the gut microbiome was concurrently modelled using the Simulator of the Human Microbial Ecosystem (SHIME®), using a young adult donor. Results Consistent with previous findings, Cereboost® improved working memory and attention during the immediate postprandial period; effects that were amplified following two weeks’ treatment (acute-on-chronic) compared to acute testing alone. Chronic supplementation improved cognition on an acetylcholine-sensitive attention task and improved mental fatigue and self-assurance aspects of mood. The parallel in vitro study revealed significantly increased acetate, propionate, and butyrate levels in simulated proximal and distal colon regions, linked with observed increases in Akkermansia muciniphila and Lactobacillus . Conclusion This study confirmed the promising effects of Cereboost® on cognitive function and mood, while suggesting a possible link to alterations of the gut microbiome and modulation of acetylcholine. Further studies will be required to unravel the underlying mechanisms that are involved. Registration The study was pre-registered at ClinicalTrials.gov on 6th July 2018 (Identifier: NCT03579095).
... As shown in Fig. 1C, R. crenulata and R. rosea share similar feature in constituent subgroups including flavonoids and their glycosides, acyclic alcohol derivatives, cinnamic alcohol derivative, phenylethane derivatives, gallic acid and its derivatives, benzyl and phenol derivatives, lignin, phenylpropanoid derivatives, nitrile derivatives, and other compounds, except that the number of lignin compounds from R. crenulata (29 lignins reported) is higher than that of R. rosea (3 lignins reported). In addition, since salidroside is believed to be the main active constituent of Rhodiola species and rosavins are the specific marker of R. rosea, the quality control standard of R. rosea extracts is usually set to contain a minimum of 3% rosavins and 0.8-1% salidroside as the ratio of these two compounds, which exist in wild R. rosea roots is about 3: 1 [12,32]. While for R. crenulata in Chinese Pharmacopoeia (version 2020), it is stipulated that at least 0.5% of salidroside in its dry root and rhizome should be contained [33]. ...
Article
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The desire to extend the wisdom of traditional health systems has motivated the trade of many phytomedicine on a global scale for centuries, especially some dietary herbs, making a great overlap exits between western and eastern phytomedicine. Despite the communication since ancient times, a key disconnect still exists in the dialog among western and eastern herbal researchers. There is very little systematic effort to tap into the friction and fusion of eastern and western wisdom in utilizing phytomedicine. In this review, we analyzed the similarities and differences of three representative phytomedicine, namely Rhodiola , seabuckthorn, and fenugreek, aiming to open up new horizons in developing novel health products by integrating the wisdom of the east and the west.
... Salidroside is a natural phenolic compound widely existed in the plants from Rhodiola and Ligustrum species. It has been reported with various activities and broad pharmacological application prospect, such as anti-age [9], anti-fatigue [10], anti-cancer [11], anti-myocardial ischemia-reperfusion injury [12], anti-inflammatory [13], improving glucose and lipid metabolism [14,15], anti-arrhythmia [16] and enhancing angiogenesis [17]. Recently, we found that salidroside ameliorated atherosclerosis-induced disturbances on glyerolipid and glycerophospholipid metabolism in liver [18]. ...
Article
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Salidroside is a kind of phenylethanoid glycoside and widespread in the plants from Rhodiola and Ligustrum species. Our previous study has reported that salidroside can prevent atherosclerosis progression by ameliorating glyerolipid and glycerophospholipid metabolism in apoE-deficient (apoE−/−) mice. However, its effect on neutral lipids and underlying mechanism remains largely unclear. Here we investigated the molecular mechanism of salidroside action from the perspective of metabolic regulation by integrating metabonomics and transcriptomics pattern. The results showed that salidroside significantly reduced cholesterols, esterified cholesterols, fatty acids, unsaturated fatty acids and triacylclycerols biosynthesis in liver through down-regulating the genes expressions of sterol regulatory element-binding proteins (Srebf1 and Srebf2). The expressions of SREBPs targeted and downstream genes, such as the encoding genes of fatty acid synthase (Fasn), glycerol-3-phosphate acyltransferase (Gpam), stearoyl-CoA desaturase (Scd), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), and proprotein convertase subtilisin/kexin type 9 (Pcsk9), were also inhibited after salidroside administration. ATP citrate lyase gene (Acly) that encodes an important enzyme producing acetyl-CoA for cholesterol and fatty acid biosynthesis significantly decreased after treatment as well. Moreover, one of ketone body products, 3-hydroxybutyrate, was significantly up-regulated in drug-treated group, indicating that fatty acid degradation was accelerated by salidroside at the same time. Our findings identify salidroside as a regulator of lipid homeostasis in atherosclerotic mice, suggesting its potential to be an alternative medicine for lowering the risks of atherosclerosis-related diseases.
... Sal, a principal physiologically active constituent from Rhodiola genus herb drug which has been widely verified to be no toxicity or less side effects in a multitude of animal experiments and clinical trials [158,[260][261][262][263][264], is recognized as a safe natural ingredient agent similarly. Sal exerted no genotoxicity even at a high dose of 1.5 g/kg while daily dosing for 3 days in mice [265]. ...
Article
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Salidroside (Sal) is a bioactive extract principally from traditional herbal medicine such as Rhodiola rosea L., which has been commonly used for hundreds of years in Asia countries. The excellent neuroprotective capacity of Sal has been illuminated in recent studies. This work focused on the source, pharmacokinetics, safety and anti-ischemic stroke (IS) effect of Sal, especially emphasizing its mechanism of action and BBB permeability. Extensive databases, including Pubmed, Web of science (WOS), Google Scholar and China National Knowledge Infrastructure (CNKI), were applied to obtain relevant online literatures. Sal exerts powerful therapeutic effects on IS in experimental models either in vitro or in vivo due to its neuroprotection, with significantly diminishing infarct size, preventing cerebral edema and improving neurological function. Also, the findings suggest the underlying mechanisms involve anti-oxidation, anti-inflammation and anti-apoptosis by regulating multiple signaling pathways and key molecules, such as NF-κB, TNF-α and PI3K/Akt pathway. In pharmacokinetics, although showing a rapid absorption and elimination, bioavailability of Sal is elevated under some non-physiological conditions. The component and its metabolite (tyrosol) are capable of distributing to brain tissue and the later keeps a higher level of concentration. Moreover, Sal scarcely has obvious toxicity or side effects in a variety of animal experiments and clinical trials, but combination of drugs and perinatal use of medicine should be taken more attentions. Finally, as an active ingredient, not only is Sal isolated from diverse plants with limited yield, but also large batches of the products can be harvested by biological and chemical synthesis. With higher efficacy and better safety profiles, Sal could sever as a promising neuroprotectant for preventing and treating IS. Nevertheless, further investigations are still required to explore the pharmacodynamic and pharmacokinetic properties of Sal in the treatment of IS.
... The improvement in QOL was observed only in the emotional and physical health domains of QOL ( Figures 5 and 6), but not in the social and environmental domains (Supplement 2). This observation is in line with several previous studies on the adaptogenic activity of Rhodiola and its beneficial effect on stress, as well as mental, behavioral, and aging-related disorders [30,[35][36][37][38][41][42][43][44][45][46]. ...
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Background: The aim of this study was to assess the efficacy and safety of a new herbal preparation (Menopause Relief EP®), the hybrid combination of Actaea racemosa L. (black cohosh, BC) and Rhodiola rosea L. (RR) root extracts, compared with the most effective dose of BC extract in women with menopausal complaints. Methods: A total of 220 women were randomly assigned to receive two capsules either BC (6.5 mg), BC500 (500 mg), Menopause Relief EP® (206,5), or placebo once per day for 12 weeks. The efficacy endpoints were relief of menopausal symptoms, measured using the Kupperman Menopausal Index (KMI), Menopause Relief Score (MRS), and menopause Utian Quality of Life (UQOL) index. Results: The menopause symptom relief effects of RR-BC were significantly superior in all tests to the effects of BC and placebo after their repeated administration for 6 and 12 weeks. There was no statistically significant difference between the effects of BC and BC500 over time. RR-BC significantly improved the QOL index in patients, compared to BC, BC500, and placebo, mainly due to the beneficial effects on the emotional and health domains. Conclusions: BC is more effective in combination with RR in relief of menopausal symptoms, particularly psychological symptoms.
... Several studies have demonstrated its various biological properties, such as anti-inflammation, anti-fatigue, anti-stress, anti-hypoxia and anti-aging. It can reduce excessive blood lipids which results in improved blood circulation and enhanced immunity [18][19][20] . Recent studies have also demonstrated its multiple cardioprotective effects both in vivo and in vitro. ...
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Salidroside (SAL) is the major ingredient of Rhodiola rosea, and has been traditionally used in Chinese medicine for decades. Numerous studies have demonstrated the protective effects of SAL for myocardial ischemia. However, it is yet to be deciphered whether SAL has cardioprotective effects after myocardial infarction (MI) in vivo. In the present study, we established a mouse MI model via coronary artery ligation. The aim was to investigate whether SAL treatment could reduce mortality, improve cardiac function and attenuate myocardial remodeling in MI mice. Post-surgery, mice were randomly administered SAL or normal saline. After 21 days, SAL was found to significantly reduce mortality, improve cardiac function, reduce fibrosis and infarct size compared to normal saline. In addition, oral administration of SAL could attenuate myocardial inflammation and apoptosis and promote angiogenesis. SAL down-regulated the expression levels of TNF-α, TGF-β1, IL-1β, Bax and up-regulate the expression of Bcl-2, VEGF, Akt and eNOS. These results indicated that SAL could alleviate the pathological processes of myocardial remodeling in MI mice, and may be a potentially effective therapeutic approach for the management of clinical ischemic cardiovascular diseases.
... Some clinical studies have confirmed that salidroside is effective in patients with mild to moderate depression, the effect is not as good as sertraline, but its side effects are small (Mao et al., 2015). There is also clinical evidence that salidroside plays a therapeutic role in anti-fatigue (Darbinyan et al., 2000), which indicates that salidroside can be used as a widely used drug to prevent or treat neuropathy. ...
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Salidroside, a phenolic compound widely existing in tubers of Rhodiola plants, has been found to have many important biological activities recently. This review summarizes the chemical synthesis and biosynthesis methods of salidroside, and introduces its pharmacological effects on diseases of liver, kidney, nervous and cardiovascular systems. A significant of studies have shown that salidroside has treatment effects on neurological diseases such as hypoxic-ischemic brain and degenerative diseases. It can prevent cardiovascular diseases by protecting cardiomyocytes and vascular endothelial cells. Salidroside can inhibit the release of oxidative stress and inflammatory factors, hence exerting protective function on liver and kidney. In addition, salidroside displays an anti-inflammatory effect by regulating the signaling pathways of NF-κB, JAK2-STAT3 and AMPK-SirT1. It can also promote cancer cell apoptosis and inhibit cancer cell proliferation. In conclusion, although the multiple bioactivities of salidroside are conformed, the clinical data are insufficient and needs to be concerned in the future.
... Preclinical in vivo and ex vivo studies in animal models and experiments on cell lines have highlighted several biochemical and pharmacological stressreducing properties of R. rosea extracts (Abidov, Crendal, Grachev, Seifulla, & Ziegenfuss, 2003;Olsson, von Scheele, & Panossian, 2009;Panossian, Hambardzumyan, Hovhanissyan, & Wikman, 2007;Panossian, Hovhannisyan, Abrahamyan, Gabrielyan, & Wikman, 2009). In clinical studies, various extracts of R. rosea were found to be effective and safe, improving mental work capacity, concentration, task performance, fatigue, burnout symptoms, and overall mood, besides reducing stress level and self-reported mild anxiety (Cropley, Banks, & Boyle, 2015;Darbinyan et al., 2000;Edwards, Heufelder, & Zimmermann, 2012;Kasper & Dienel, 2017;Panossian, Wikman, Kaur, & Asea, 2009;Punja, Shamseer, Olson, & Vohra, 2014). R. rosea was approved by the European Medicines Agency Stress response typically begins with activation of the hypothalamus-pituitary-adrenal (HPA) axis, one of the main stress response pathways, and the production of corticosteroids (Anghelescu et al., 2018;Subhani et al., 2018). ...
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Rhodiola rosea L. (R. rosea) is an adaptogenic plant increasing body resistance to stress. Its efficacy has been evidenced mainly in chronic stress models, data concerning its effect in acute stress and underlying mechanisms being scarce. The objective was to investigate the effect of repeated doses of a R. rosea hydroethanolic root extract (HRE) on hypothalamic pituitary adrenal response in a murine model of acute mild stress and also the mechanisms involved. Stress response was measured in Balb/c mice having received by gavage HRE (5 g/kg) or vehicle daily for 2 weeks before being submitted to an acute mild stress protocol (open‐field test then elevated plus maze). Corticosterone was measured in plasma from mandibular vein blood drawn before and 30, 60, and 90 min after initiation of the stress protocol. Mice were sacrificed at 90 min, and the hippocampus, prefrontal cortex, and amygdala were excised for high‐frequency RT‐PCR gene expression analysis. At 30 min after acute mild stress induction, corticosterone level in mice having received the HRE was lower than in control mice and comparable to that in nonstressed mice in the HRE group. HRE administration induced brain structure‐dependent changes in expression of several stress‐responsive genes implicated in neuronal structure, HPA axis activation, and circadian rhythm. In the acute mild stress model used, R. rosea HRE decreased corticosterone level and increased expression of stress‐responsive genes, especially in the hippocampus and prefrontal cortex. These findings suggest that R. rosea HRE could be of value for modulating reactivity to acute mild stress. In this study, R. rosea HRE decreased corticosterone level and increased expression of stress‐responsive genes, especially in the hippocampus and prefrontal cortex after an acute mild stress. These findings suggest that R. rosea HRE could be of value for modulating reactivity to acute mild stress.
... The pharmacological effects of R. rosea act as tranquilizers, to enhance the development of avoidance reflexes based on positive ammunition Petkov VD et al., 1990;Baranov VB et al., 1994;Komar VV et al., 1981;Stancheva SL et al., 1987;Lazarova MB., et al., 1986) [21,22,23,24,25,26] . R. rosea stimulated norepinephrine, dopamine, Serotonin and nicotinic cholinergic effects in Central Nervous System. ...
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Rhodiola rosea L. is also called Golden root, Arctic root or Rose root. Its roots are act as adaptogens to help our body adapt to resist physical, chemical and environmental stress. Rhodiola rosea are rich in polyphenols, salidroside, tyrosol and other primary bioactive compounds. This review gives the information about the bioactivities it includes in anti-depressant, Anti-oxidant, Antifatique, Adaptogenic, anticancer activities and its current and future medical applications.
... It has been reported that many natural herbal compounds share the chemo-preventive and chemo-therapeutic properties including anti-tumor effects [4][5][6]. Salidroside, an active ingredient isolated from dried roots, rhizomes or whole plants of Rhodiola rosea, has been identified to display a wide range of pharmacological activities, like anti-aging, anti-hypoxia, antiinflammation, neuroprotection activities, potentiating the immune function, enhancing the body's resistance to fatigue, protecting body from irradiation injury and anti-tumor [7][8][9][10][11][12]. Regarding its anti-tumor properties, a preliminary study has reported that Salidroside suppressed the proliferation of various human cancer cells such as human mammary adenocarcinoma (MCF-7), human hepatocellular carcinoma (HHCC), human lung adenocarcinoma (A549), and human malignant glioma (BT-325) cells [13]. ...
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Salidroside is an active ingredient extracted from Rhodiola rosea that has anti-tumor activities. The current paper attempted to assess the impact of Salidroside on gastric cancer (GC) and explore the potential mechanism. GC cell lines (SNU-216 and MGC803) and gastric epithelial cell line GES-1 were treated with Salidroside. CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were respectively performed to evaluate GC cells phenotype. qRT-PCR and western blot were conducted to reveal the downstream genes and signaling of Salidroside. We found that 800 μM Salidroside was capable of reducing GC cells viability, while has no such impacts on GES-1 cells. Salidroside inhibited GC cells proliferation, migration, invasion and promoted apoptosis, which coupled with the down-regulation of p21, Bcl-2, MMP2, RhoA, p-ROCK1, Vimentin and the up-regulations of CyclinD1, Bax, cleaved caspases. miR-99a was found to be highly expressed in response to Salidroside treatment. Besides, the inhibition of MAPK/ERK and PI3K/AKT signaling induced by Salidroside was attenuated by miR-99a silence and in this process, IGF1R worked as a target of miR-99a. The anti-GC effect of Salidroside was also confirmed in a mouse model of GC. The promoting effect of Salidroside on miR-99a expression was also verified in vivo. Furthermore, Salidroside promoted the cisplatin-sensitivity of SGC7901/DDP cells. In conclusion, this study demonstrated that Salidroside possessed anti-GC effects through regulating miR-99a/IGF1R axis and inhibiting MAPK/ERK and PI3K/AKT pathways.
... "Treatment with RR standardized extract of rhizome significantly improved the perceptive and cognitive cerebral functions in young, healthy physicians, during night duty, so RR can reduce general fatigue under certain stressful conditions" (Darbinyan et al., 2000). "Approximately 140 compounds were isolated from roots and rhizome of RR and a number of clinical trials demonstrate that repeated administration of RR extract SHR-5 exerts an anti-fatigue effect that increases mental performance (particularly the ability to concentrate in healthy subjects), and reduces burnout in patients with fatigue syndrome; several mechanisms of action are possible contributors: interactions with HPA-system (cortisol-reducing), protein kinases p-JNK, nitric oxide, and defense mechanism proteins" (Panossian et al., 2010). ...
... In Russia, R. rosea is registered as an official medicament (Shikov et al., 2014). Clinical studies demonstrated beneficial effects on physical and mental performance as well as on fatigue and mild depression (Darbinyan et al., 2000;Hung et al., 2011;Olsson et al., 2009;Panossian and Wagner, 2005). Using animal experiments, bioassayguided fractioning helped to identify several active compounds in R. rosea such as salidroside, rosavin, rosiridin (Chiang et al., 2015;Dimpfel et al., 2018) and very recently ferulic acid eicosyl ester (Michels et al., 2018). ...
Article
Ethnopharmacological relevance: The plant arctic root (Rhodiola rosea, L.) is growing in northern regions of Europe, Asia and North America. Extracts of R. rosea are used in traditional medicine for various conditions related to nervous system function. According to scientific studies from the last decades, the plant might have potential for use in the treatment of memory impairments, stress and depression, but reports concerning other neuropsychiatric disorders are scarce. Aim of the study: In this context, our study aimed to examine potential antipsychotic-like effects of R. rosea root extract. Materials and methods: We tested the effects of R. rosea root extract on prepulse inhibition in rats and mice. Prepulse inhibition is an established operational measure of sensorimotor gating, which is impaired in schizophrenia and other psychotic disorders. Results: R. rosea root extract increased prepulse inhibition in rats and mice. Interestingly, the R. rosea extract had stronger effects in those individual animals that had low baseline levels of prepulse inhibition. Therefore, we performed further experiments in which we pharmacologically induced a prepulse inhibition deficit by two different psychostimulants, either the dopamine D2 receptor agonist apomorphine or the NMDA receptor antagonist dizocilpine (MK-801). Pre-treatment with the R. rosea extract significantly restored both, apomorphine- and dizocilpine-induced prepulse inhibition deficits. Conclusions: The present study demonstrates that R. rosea extract robustly reverses prepulse inhibition deficits in rodents. This suggests antipsychotic-like effects of R. rosea extract. Future studies should focus on the pharmacological mechanisms underlying these effects.
... Its mechanism may be related to its ability to increase the permeability of the blood-brain barrier to the precursors of dopamine (DA) and 5-HT [26]. The administration of Rhodiola rosea has also been shown to improve concentration and reduce the stress response [27,28]. ...
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Aging is a progressive accumulation of changes in the body, which increases the susceptibility to diseases such as Alzheimer’s disease, Parkinson’s disease, cerebrovascular disease, diabetes, and cardiovascular disease. Recently, Chinese medicinal herbs have been investigated for their therapeutic efficacy in the treatment of some aging-related diseases. Rhodiola, known as ‘Hongjingtian’ in Chinese, has been reported to have anti-aging activity. Here, we provide a comprehensive review about its origin, chemical constituents, and effects on aging-related diseases.
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fonksiyonel tıp: Cilt hastalıkları Ürolojik hastalıklar
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Background : Adaptogens are generally referred to the substances, mostly found in plants, which non-specifically increase resilience and chances of survival by activation of signaling pathways in affected cells. Purpose : This literature review was conducted to summarize the investigation, until March 2021, on selected adaptogenic plants and plant-derived substances. Study Design : Electronic databases were searched (up to March 2021) for in vitro and animal studies, as well as clinical trials. Moreover, all modes of action connected with the adaptogenic effects of plants and phytochemicals were collected. Methods : The search of relevant studies was performed within electronic databases including Scopus, Science Direct, PubMed, and Cochrane library. The most important keywords were adaptogen, plant, phytochemical, and plant-derived. Results : The most investigated medicinal herbs for their adaptogenic activity are Eleutherococcus senticosus, Panax ginseng, Withania somnifera, Schisandra chinensis, and Rhodiola spp., salidroside, ginsenosides, andrographolide, methyl jasmonate, cucurbitacin R, dichotosin, and dichotosininare are phytochemicals that have shown a considerable adaptogenic activity. Phytochemicals that have been demonstrated adaptogenic properties mainly belong to flavonoids, terpenoids, and phenylpropanoid glycosides. Conclusion : It is concluded that the main modes of action of the selected adaptogenic plants are stress modulatory, antioxidant, anti-fatigue, and physical endurance enhancement. Other properties were nootropic, immunomodulatory, cardiovascular, and radioprotective activities.
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Salidroside is a naturally occurring phenylpropanoid glycoside which widely used in food and cosmetics. The development of microbial synthesis of salidroside is limited due to the low titer and the addition of inducers and antibiotics. Based on our previously constructed high tyrosol-producing recombinant Escherichia coli, we identified the catalytic activity of glycosyltransferase UGT85A1 was high. The strain carrying plasmid pKK223-UGT85A1 produced 2.5 g/L of salidroside in shake flask. To construct a stable, non-inducible, antibiotic-free salidroside-producing strain, UGT85A1 gene was integrated into genomic sites and the single-copy strain could only produce about 120 mg/L of salidroside. Therefore, we designed a multi-copy integration strategy and obtained an eight-copy number recombinant strain 5A8S. The production of salidroside also increased sequentially and the strains grew well. When the strain 5A8S was cultured in a shake flask, the salidroside production reached 2.42 g/L. Then, we carried out a scale-up culture of strains 5A-UGT85A1 and 5A8S in a 5 L fermenter, and the salidroside titers were 9.48 and 9.34 g/L, respectively. In this study, a non-inducible high-yield salidroside recombinant strain was successfully constructed using a multi-copy integration strategy in the non-coding region of the genome, thus laying the foundation for efficient green biosynthesis of salidroside.
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Medicinal plants have always been prescribed around the world with therapeutic purposes for various diseases and disorders related to their profile of biologically active substances and health-promoting effects. Meantime, Rhodiola rosea has been of particular importance among physicians, researchers and the general public. Accordingly, the present perspective aimed to explore the beneficial effects of this plant by focusing on in vitro and in vivo studies, and nutritional effects. The current work also provides a comprehensive analysis of the Rhodiola rosea studies in the literature throughout a quantitative literature research analysis approach. The literature search was carried out by means of the Scopus database to retrieve Rhodiola rosea-related publications. VOSviewer software (v.1.6.16, 2020) was used to extract and elaborate bibliometric data. 958 publications ranging from 1966 to 2021 were given by the literature search. Technological prospecting for patents was also assessed.
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Rhodiola (Rhodiola rosea) has been shown to protect the nervous system, heart, and liver and to produce antimutagenic and anticancer effects. It may be beneficial for ischemic heart disease, premature ejaculation, anxiety, depression, cognitive performance, xeroderma, stress, burnout, chronic fatigue, athletic performance, chemo-induced myocarditis, and immune suppression. Numerous studies show that rhodiola can create both a stimulating and a sedating effect on the central nervous system, depending on dosage. Thus, it also has traditional and modern usage as an anti-fatigue adaptogen. This chapter examines some of the scientific research conducted on rhodiola, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of rhodiola’s use in treating cardiovascular, genitourinary, psychiatric, dermatological, vitality, infectious, and oncological disorders. Finally, the chapter presents a list of rhodiola’s active constituents, different Commonly Used Preparations and Dosage, and a section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
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Background: Dietary supplements promoted for brain health and enhanced cognitive performance are widely available. Claims made for these products are directed not only to the elderly wishing to prevent or mitigate cognitive decline, but also young healthy populations looking to boost their cognitive performance. It is unclear whether these claims made on product bottles and through advertising match the science. Objectives: To explore the evidence on the efficacy and safety of single dietary supplement ingredients frequently marketed with claims of enhanced cognitive performance among healthy adults. Design: A systematic review. Results: Nine of 54 dietary supplement ingredients identified through a scoping review met the eligibility criteria with at least 3 published studies identified per ingredient, yielding 69 unique publications. Ingredients evaluated included Bacopa monnieri, choline, creatine, omega-3 fatty acids, Ginkgo biloba, ginseng, Rhodiola rosea, tyrosine, and valerian root, all in supplement form and compared with a placebo, at various serving sizes and durations of use. Conclusions: The low level of certainty in the state of the science, coupled with not always knowing what is in a dietary supplement product, make weighing risks and benefits difficult; these data hinder the ability to develop recommendations about using such ingredients for consumers interested in boosting their cognitive performance. Whereas certain trends regarding promising serving sizes or duration for use, are pointed to in this synthesis, when combined, studies are inconsistent and imprecise, and many are methodologically flawed. Potential solutions to address research gaps are offered, for future research next steps, which is needed to strengthen the evidence and inform decisions.
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Background & aims: Nonalcoholic steatohepatitis (NASH) is becoming a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Salidroside (p-hydroxyphenethyl-β-d-glucoside) has various biological and pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. However, the therapeutic effect and underlying molecular mechanism of salidroside in NASH remain to be further clarified. Methods & results: In this study, we found that salidroside alleviated lipid accumulation and inflammatory response in primary hepatocytes after palmitic acid/oleic acid (PO) stimulation. In addition, salidroside effectively prevented high-fat/high-cholesterol (HFHC) diet induced NASH progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation and fibrosis. Mechanistically, integrated RNA sequencing and bioinformatic analysis showed that salidroside promoted AMPK signaling pathway activation in vitro and in vivo, and this finding was further verified by determining the phosphorylation levels of AMPK. Furthermore, the protective effects of salidroside on lipid accumulation and inflammation in hepatocytes and livers induced by PO- or HFHC- stimulation were blocked by AMPK interruption. Conclusion: Our studies demonstrate that salidroside protects against metabolic stress-induced NASH progression through activation of AMPK signaling, indicating that salidroside could be a potential new drug component for NASH therapy.
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Background: Rhodiola is a worldwide used medicinal plant for its various medicinal functions, and the number of randomized controlled trials (RCTs) of Rhodiola is increasing in recent years. This study aims to evaluate the reporting quality and risk of bias of the current RCT reports of different Rhodiola species. Methods: Six databases including Embase, PubMed, Web of Science, the Cochrane Library, ClinicalTrial.gov, and China National Knowledge Infrastructure were searched to identify RCTs that used Rhodiola as a single intervention and were published in English or Chinese from inception to December 2020. The Consolidated Standards of Reporting Trials (CONSORT) 2010 statement was used as the checklist for assessment, and a scoring system was applied to the evaluation of RCTs. Score 0 represents no reporting or inadequate reporting, and score 1 represents adequate reporting. The risk of bias of the included studies was also assessed using the Cochrane Risk of Bias tool. Results: A total of 39 RCTs were included in this study, including 23 RCTs of Rhodiola rosea (R. rosea), 8 RCTs of Rhodiola crenulata (R. crenulata), and 8 RCTs of Rhodiola wallichiana (R. wallichiana). None of the included studies met all the CONSORT statement criteria, and the reporting quality of RCTs of the three Rhodiola species was all generally poor. Based on the risk of bias assessment, the majority of included studies were judged to have an unclear risk of bias in most domains due to inadequate reporting. Conclusions: There is inadequate reporting among the included RCTs of different Rhodiola species, and RCTs of Rhodiola with higher reporting quality and better methodological quality are needed.
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Thyroid gland is vascular gland located on the right and left sides of the end of the larynx the beginning of the trachea. It produces, stores, secretes thyroid hormones. Thyroid hormones are important for growth, development, metabolism. Thyroid gland dysfunctions: hypothyroidism, hyperthyroidism, euthyroid, goiter, thyroid nodules, thyroiditis, thyroid cancers. Any problems in the synthesis, secretion of thyroid hormone may be the cause of these diseases. Abnormalities in the synthesis, secretion of thyroid hormones lead to both changes in the basal metabolic rate and health problems. People resort to natural methods such as treatment with plants to improve thyroid symptoms that occur for different reasons. As a result of the literature reviews, few clinical studies have been identified regarding the effective and reliable use of plants in thyroid dysfunction. In this review, these clinical studies and ethnobotanical, ethnopharmacological data of these plants were examined in more detail. Depending on the intended use, the effects of medicinal plants on thyroid gland metabolism, thyroid hormones, treatment of thyroid gland dysfunctions are included. In our study, there are 68 different plants from 42 different families that are thought to be beneficial in thyroid dysfunction and 36 in vivo studies. These plants have generally been found to be effective in hypothyroidism or hyperthyroidism. As a result of literature reviews, it is determined that the leaves of plants are used for water extracts. It is thought that this review may shed some light on further research on the treatment of thyroid dysfunction with herbal medicines. Keywords: Thyroid; phytotherapy; hypothyroidism; hyperthyroidism; herbal medicine
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Salidroside has been identified as one of the most potent compounds isolated from various Rhodiola plants, which have been used for a long time as adaptogens in traditional Chinese medicine. However, due to the severe growing environment of herbal medicine and large-scale excavation, the content of natural salidroside is extremely small. Most of the previous studies focused on herbal medicine, and there were few reviews on the synthesis of its main active ingredient salidroside. This paper presents different synthetic routes of salidroside to resolve the contradiction between supply and demand and lays the foundation for new drug research and development. Furthermore, emerging evidence indicates that salidroside, a promising environmentally-adapted drug with low toxicity and few side effects, possesses a wide spectrum of pharmacological properties, including activities on the cardiovascular system and central nervous system, anti-hypoxia, anti-fatigue and anti-aging activities, anticancer activity, anti-inflammatory activity, antioxidant activity, antivirus and immune stimulation activities, antidiabetic activity, anti-osteoporotic activity, and so on. Although the former researches have summarized the pharmacological effects of salidroside, focusing on the central nervous system, diabetes, and cancer, the overall pharmacological aspects of it have not been analyzed. This review highlights biological characteristics and mechanisms of action from 2009 to now as well as toxicological and pharmacokinetic data of the analyzed compound reported so far, with a view to providing a reference for further development and utilization of salidroside.
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The rich botanical biodiversity of high-altitude Trans-Himalayan region has gained a lot of importance in recent years owing to its immense curative and therapeutic potential. Rhodiola imbricata is one such exceptionally celebrated plant widely acknowledged by the scientific community and pharmaceutical industries. The plant offers a phenomenal range of properties such as antioxidant, antiaging, radioprotective, etc., along with treating a multitude of disorders. The copious traditional knowledge, short growing season, and availability of novel bioactive compounds have led to indiscriminate harvesting of the plant leading to its overexploitation by the local farmers. This chapter provides detail description and composition of phytochemicals and bioactive compounds and highlights prophylactic significance and application of advanced tissue culture technologies for sustainable growth and efficient utilization of the plant for benefitting the larger consumer base.
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The chapter reviews the overall neuronal molecular mechanisms of Bacopa monnieri with respect to cognitive performance. It starts with defining cognition, and how interruption in signal transduction can cause cognitive impairment. Then the factors influencing signal transduction and regulation of those factors are briefed to give a glimpse on cascade involved in signal transduction and their importance in governing the cognitive performance. The drugs and nutraceuticals commonly used as cognition enhancers and their mechanisms of action are covered in brief before taking up details of B. monnieri. Later, effect of B. monnieri on various factors contributing to signal transduction like neurotransmitters, receptors, second messenger system, gene expression, neuronal structural factors, neuronal connections, cerebral blood flow and neuroprotection are detailed to understand the neuronal molecular mechanisms involved in improving cognitive performance. Summary of this review points toward strong scientific substantiation available in the literature to justify the use of B. monnieri in dietary and food supplements intended for cognitive health.
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Plants are the primary source of the therapeutic needs for mankind since ancient times and capable of growing under extreme conditions. The diversity in ecological growing conditions and also variability in altitude that ranges from 100 to 7500 m above the sea level introduce diverse kinds of medicinal plants in the higher altitude. In Indian Himalayan region, there are a number of medicinal plants growing wildly such as Aconitum heterophyllum, Hippophae rhamnoides, Inula racemosa, Rhodiola rosea, and Sinopodophyllum hexandrum. Aconitum heterophyllum has active alkaloids such as lycoctonine which shows significant activity against Pseudomonas aeruginosa and Salmonella typhi. Analgesic and anti-inflammatory activities are significantly shown by some other alkaloids such as aconitine and mesaconitine derivatives. Inula racemosa contains a large amount of sesquiterpene lactones such as alantolactone and isoalantolactone and a large number of biological activities such as antimalarial, antifungal and hypoglcaemic and Sinopodophyllum hexandrum contains a variety of bioactive molecules such as flavonoids and lignans which possess antioxidant and antiapoptotic potential and hence help in radio-protection. The root of Rhodiola rosea contains more than 140 active constituents, and among them the two most potent are rosavin and salidroside. These constituents help in decreasing stress, improve brain function, reduce symptoms of depression etc. The adverse conditions in higher altitude is due to the presence of ultraviolet (UV) filters, potent antioxidants, free radical quenchers and antifreeze carbohydrates, and the plants growing in such habitat adapt themself to different mechanisms of metabolite synthesis. This is the major reason for the availability of diverse and unique chemical entities in the high-altitude plants. On the other hand, these processes are not shown by plants growing in low altitude. Their biochemical machinery has been able to bear the aggressive climatic conditions by the way of new biosynthetic twists leading to new molecular skeletal, which are absent in the lower region plants. High-altitude plants gain a lot of economic and medicinal importance. The amount and variety of chemical constituents present in high-altitude plants differ from plants growing in lower region, and this attracts researchers to investigate and explore their medicinal applications for human health care.
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The purpose of the present study was to examine the acute effects of an herbal supplement containing a 70:30 blend of Rhaponticum carthamoides extract and Rhodiola rosea extract, respectively, on performance fatigability and the affective responses prior to and following exercise. Thirty men (age = 22.3 ± 4.1 years) volunteered for this randomized, placebo-controlled, double-blind, cross-over study. Following familiarization, participants visited the laboratory on three separate occasions where they consumed one 350 mg dose, a 175 mg dose of the supplement plus 175 mg of maltodextrin, or a placebo. Participants completed feeling, arousal, and mood surveys at supplement ingestion and following testing. Ninety minutes following ingestion, participants performed five sets of 30 maximal, concentric, leg extension muscle actions at 180°/sec, with one minute of rest between sets. Peak torque, average torque, and total work were calculated for each set, and the rating of perceived exertion (RPE) was assessed after each set. Data were analyzed with a repeated measures analysis of variance and intent-to-treat approach. For the performance variables, there was no interaction (p ≥ 0.317) or treatment effect (p ≥ 0.660), however, all torque variables decreased across sets and plateaued at sets 4-5, whereas RPE increased across sets (p < 0.001). For the affective responses, there was no interaction (p ≥ 0.781) or treatment effect (p ≥ 0.314); however, participants felt better, had an improved mood, and felt more aroused following testing (p < 0.047). This combination of herbal extracts likely does not acutely influence performance fatigability during high-intensity, repeated muscle actions.
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Background: The current and potential uses of adaptogens are mainly related to treatment of stress-induced fatigue, impaired cognitive function, mental illness, and behavioral- and age-related disorders. However, clinical evidence regarding the efficacy of adaptogens is limited. The primary aim of this study is to determine whether a combination of adaptogenic plant extracts from Andrographis paniculata and Withania somnifera (Adaptra® Forte) could be used as effective and safe treatment for impaired cognitive, memory, or learning ability functions and sleep disorders. Methods: The changes in electroencephalogram (EEG) frequency ranges in 17 different brain regions, psychometric tests of cognitive performance, as well as standard questionnaires of assessment of mood and sleep were measured after single and repeated administration of Adaptra® or placebo for four weeks and after a two-week treatment-free follow-up period within a randomized, double-blind, placebo-controlled two-armed cross-over study. Results: Adaptra® Forte significantly improved cognitive performance in the d2-Test for attention and the concentration performance test after four weeks' treatment, and was positively correlated with increases in δ and θ power in the quantitative EEG compared with placebo during cognitive challenges. Conclusion: The results of this study suggest that Adaptra® Forte exhibits a calming and anxiolytic effect without sedation, and is associated with overall stress-protective activity.
Article
Background: We performed a proof of concept trial to evaluate relative safety and efficacy of Rhodiola Capsule for mild to moderate major depressive disorder(MDD). Methods: It is a randomized double-blind placebo-controlled clinical trial which 100 patients were randomized to 12 weeks into three groups. One of which (group A: 33 patients) received one sertraline and two placebos(0.6 g/day) tablets daily, a second (group B: 33 patients) received one sertraline and two Rhodiola capsules (0.6 g/day) daily, and a third (group C: 34 patients) received one sertraline,one placebo tablet and one tablet of Rhodiola capsule (0.3 g/day)daily. Changes over time in Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression Change (CGI/C) scores were examined. Significant post-treatment improvements were observed for both groups (Rhodiola Capsule) in HAMD, BDI, and CGI scores. The decline in HAMD, BDI, and CGI scores was greater for group B versus group A and C.While the CGI (versus group A) were greater for group B and C. Results: Statistically significant reductions were observed for HAM-D, BDI, and CGI scores for all treatment conditions with significant difference between groups. The decline in HAM-D, BDI, and CGI scores was greater for group B versus group C and A. Conclusions: It is concluded that the Rhodiola capsule shows anti-depressive potency in patients with depression disorder when administered in dosages of either 0.3 or 0.6 g/day over a 12-week period.Rhodiola capsule can improve the quality of life and clinical symptoms.The high doses of Rhodiola capsule are better than the lower doses.
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Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to 2 experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.
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Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's disease (AD), Parkinson's disease (PD) and spinal cord injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the traditional Chinese medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.
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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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Rhodiola species, belonging to the family Crassulaceae, have long been used as an adaptogen, tonic, antidepressant, and antistress medicine or functional food in Asia and Europe. Due to the valuable application, the growing demand of Rhodiola species has led to a rapid decrease in resource content. This review aims to summarize the integrated research progress of seven mainstream Rhodiola species. We first outline both traditional and current use of Rhodiola for the treatment of various diseases. A detailed summary and comparison of chemical, pharmacological, toxicological, and clinical studies of various Rhodiola species highlight recent scientific advances and gaps, which gives insights into the understanding of Rhodiola application and would be helpful to improve the situation of biological resources and diversities of Rhodiola plants.
Article
The term adaptogen has not yet been accepted in medicine. This is probably due to the difficulties in discriminating adaptogenic drugs from immunostimulators, anabolic drugs, nootropic drugs, and tonics. There can be not doubt, however, that, at least in animal experiments, there are plant drugs capable of modulating distinct phases of the adaptation syndrome as defined by Seyle. These drugs either reduce stress reactions in the alarm phase or retard / prevent the exhaustion phase and thus provide a certain degree of protection against long-term stress. The small number of drugs the antistress activity of which has been proven or reported includes, among others, the plant drugs Ginseng, Eleutherococcus, Withania, Ocimum, Rhodiola, and Codonopsis. This review summarizes the major findings of pharmacological tests and human studies carried out with these drugs. Currently used assay systems allowing detection of antistress activities are also reported. At present the most likely candidates responsible for the putative antistress activity of plant drugs are special steroids, phenylprogane compounds and lignanes, respectively. Apart from influencing activities of the pituitary-adrenal axis and inducing stress proteins, many adaptogens also possess immunomodulatory and / or anabolic activities.
The effect of alcohol-aqueous extract (1:1) from Rhodiola rosea L. roots on the processes of learning and memory is studied on rats. Several methods of active avoidance with negative and positive reinforcements are used, as well as of passive avoidance. Using the maze-method with negative (punitive) reinforcement, it has been found that Rhodiola extract in a single dose of 0.10 ml per rat essentially improves learning and retention after 24 hours. Significant improvement of the long-term memory is also established in memory tests after 10-day treatment with the same dose of the extract. In the other two doses tested (0.02 and 1.0 ml per rat) the extract has no substantial effect on learning and memory. In a dose of 0.10 ml per rat the Rhodiola extract had a favourable effect on the training process using the "staircase" method with positive (food) reinforcement as well. With the other methods used (active avoidance method with negative reinforcement "shuttle-box" and passive avoidance methods "step down" and "step through") Rhodiola extract in the dose used (0.10 ml per rat) had no substantial effect on learning and memory (a certain deterioration of the training process was even observed using the "shuttle-box" method, while the "step-down" method resulted in deterioration of the memory). The great significance of the method used for studying the effects of the pharmacological agents on learning and memory for the results obtained is evident.
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The test with running on a treadbane showed a 56% increase of working capacity in the control group of male albino mice on the 20th day of training. Oral administration of elton, leveton, phytoton, and adapton, as well as Leuzea and Rhodiola extracts and Schisandra chinensis tincture caused a statistically significant increase in the time of running on the treadbane of animals by the 10th day of medication. The increase in the working capacity of the animals was more marked by the 20th day. In the test of swimming "to the limit" adapton, phytoton, leveton, and elton increased to a greater extent the working capacity of male albino rats in diminishing succession (from 213 to 168%). Schisandra tincture and Rhodiola and Leuzea extracts also increased the swimming time of the animals by 135-159%.
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