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Monoamine oxidase inhibition by Rhodiola rosea L. roots

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Abstract

Rhodiola rosea L. (Crassulaceae) is traditionally used in Eastern Europe and Asia to stimulate the nervous system, enhance physical and mental performance, treat fatigue, psychological stress and depression. In order to investigate the influence of Rhodiola rosea L. roots on mood disorders, three extracts were tested against monoamine oxidases (MAOs A and B) in a microtitre plate bioassay. Methanol and water extracts gave the highest inhibitory activity against MAOs. Twelve compounds were then isolated by bioassay-guided fractionation using chromatographic methods. The structures were determined by 1H, 13C NMR and HR-MS. The methanol and water extracts exhibited respectively inhibitions of 92.5% and 84.3% on MAO A and 81.8% and 88.9% on MAO B, at a concentration of 100 microg/ml. The most active compound (rosiridin) presented an inhibition over 80% on MAO B at a concentration of 10(-5) M (pIC50=5.38+/-0.05). The present investigation demonstrates that Rhodiola rosea L. roots have potent anti-depressant activity by inhibiting MAO A and may also find application in the control of senile dementia by their inhibition of MAO B.

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... The ability of R. rosea to increase the non-specific resistance and exert neuroprotective properties have been primarily attributed to its capacity to influence the levels and activity of several components of the stress-response system, including monoamine neurotransmitters such as serotonin and catecholamine, and opioid peptides such as βendorphins [1,5,[20][21][22][23][24]. In small and medium doses, R. rosea administration was found to stimulate the noradrenalin, serotonin, dopamine and acetylcholine receptors in the central nervous system (CNS) [24]. ...
... The ability of R. rosea to increase the non-specific resistance and exert neuroprotective properties have been primarily attributed to its capacity to influence the levels and activity of several components of the stress-response system, including monoamine neurotransmitters such as serotonin and catecholamine, and opioid peptides such as βendorphins [1,5,[20][21][22][23][24]. In small and medium doses, R. rosea administration was found to stimulate the noradrenalin, serotonin, dopamine and acetylcholine receptors in the central nervous system (CNS) [24]. It also enhanced the effects of these neurotransmitters on the brain by increasing the permeability of the blood-brain barrier to precursors of dopamine and serotonin [25]. ...
... The molecular mechanisms involved in the antidepressant effects of R. rosea extracts have been examined by numerous preclinical studies [20,24,25,34,35]. A comprehensive review by Amsterdam and Panossian [25] reported that R. rosea stimulates the expression and release of neuropeptide-Y in neuroglial cells, controls more than 50 genes involved in the regulation of behavior, mood and depressive disorders, and is associated with certain key mediators of the stress response: regulation of the homeostasis of the hypothalamicpituitary-adrenal (HPA) axis and modulation of G-protein-coupled receptor signaling pathways [32,[34][35][36]. ...
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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.
... Dal‰ími obsahov˘mi látkami jsou i fenolické kyseliny -chlorogenová kyselina nebo hydroxyskofiicová kyselina, popfi. jiné organické kyseliny jako ‰Èavelová, citrónová, jableãná, jantarová, fumarová, kávová, gallová, a fenoly 6,12,14,15,[18][19][20][21][22][23][24][25][26][27][28][29] 29) . ...
... Dal‰ími obsahov˘mi látkami jsou i fenolické kyseliny -chlorogenová kyselina nebo hydroxyskofiicová kyselina, popfi. jiné organické kyseliny jako ‰Èavelová, citrónová, jableãná, jantarová, fumarová, kávová, gallová, a fenoly 6,12,14,15,[18][19][20][21][22][23][24][25][26][27][28][29] 29) . ...
... Nature-derived supplement products are generally a mixture of multiple bioactive compounds, all of which could potentially have drug-drug interactions with other medication. For example, van Diermen et al. [4] used dichloromethane, methanol, and water to extract components of dried and powdered roots of Rhodiola rosea and structurally identified twelve components, including salidroside. ...
... Extraction mixtures of Rhodiola rosea and twelve individual, isolated components were previously tested for MAO-A and MAO-B inhibitory potency [4]. At a concentration of 100 µg/mL crude mixtures, dichloromethane, methanol, and water extracts were found to have 50. ...
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Several studies utilizing Rhodiola rosea, which contains a complex mixture of phytochemicals, reported some positive drug-drug interaction (DDI) findings based on in vitro CYP450’s enzyme inhibition, MAO-A and MAO-B inhibition, and preclinical pharmacokinetic studies in either rats or rabbits. However, variation in and multiplicity of constituents present in Rhodiola products is a cause for concern for accurately evaluating drug-drug interaction (DDI) risk. In this report, we examined the effects of bioengineered, nature-identical salidroside on the inhibition potential of salidroside on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 utilizing human liver microsomes, the induction potential of salidroside on CYP1A2, CYP2B6 and CYP3A4 in cryopreserved human hepatocytes, the inhibitory potential of salidroside against recombinant human MAO-A and MAO-B, and the OATP human uptake transport inhibitory potential of salidroside using transfected HEK293-OATP1B1 and OATP1B3 cells. The results demonstrate that the bioengineered salidroside at a concentration exceeding the predicted plasma concentrations of <2 µM (based on 60 mg PO) shows no risk for drug-drug interaction due to CYP450, MAO enzymes, or OATP drug transport proteins. Our current studies further support the safe use of salidroside in combination with other drugs cleared by CYP or MAO metabolism or OATP-mediated disposition.
... Also, it is supposed that R. rosea lessens the transport of neuromediators in the brain [1,4,9]. R. rosea active compound rosiridin inhibited monoamineoxidases A and B in vitro, thus acting against depression and senile dementia [63]. ...
... Thus, R. rosea exhibits neuroprotective effects by reducing oxidative stress and inflammation, potentially slowing down the progression of neurological disorders [58]. It also enhances cognitive function, including memory, a ention, and learning abilities, which can benefit conditions associated with cognitive decline [63]. Additionally, R. rosea regulates mood by modulating neurotransmi ers and neuroendocrine pathways, offering potential relief for mood disorders [75,76]. ...
Article
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The roots and rhizomes of Rhodiola rosea L. (Crassulaceae), which is widely growing in Northern Europe, North America, and Siberia, have been used since ancient times to alleviate stress, fatigue, and mental and physical disorders. Phenolic compounds: phenylpropanoids rosavin, rosarin, and rosin, tyrosol glucoside salidroside, and tyrosol, are responsible for the biological action of R. rosea, exerting antioxidant, immunomodulatory, anti-aging, anti-fatigue activities. R. rosea extract formulations are used as alternative remedies to enhance mental and cognitive functions and protect the central nervous system and heart during stress. Recent studies indicate that R. rosea may be used to treat diabetes, cancer, and a variety of cardiovascular and neurological disorders such as Alzheimer’s and Parkinson’s diseases. This paper reviews the beneficial effects of the extract of R. rosea, its key active components, and their possible use in the treatment of chronic diseases. R. rosea represents an excellent natural remedy to address situations involving decreased performance, such as fatigue and a sense of weakness, particularly in the context of chronic diseases. Given the significance of mitochondria in cellular energy metabolism and their vulnerability to reactive oxygen species, future research should prioritize investigating the potential effects of R. rosea main bioactive phenolic compounds on mitochondria, thus targeting cellular energy supply and countering oxidative stress-related effects.
... The IC50 estimate of rutin, quercetin, quercitrin, and isoquercitrin on MAO-B were reported as 3.89, 10.89, 19.06, and 11.64 µM, respectively (Lee et al., 2001). MAO-A inhibition of quercetin was reported by van Diermen et al. (2009) with an 18 µM IC50 value (van Diermen et al., 2009). ...
... The IC50 estimate of rutin, quercetin, quercitrin, and isoquercitrin on MAO-B were reported as 3.89, 10.89, 19.06, and 11.64 µM, respectively (Lee et al., 2001). MAO-A inhibition of quercetin was reported by van Diermen et al. (2009) with an 18 µM IC50 value (van Diermen et al., 2009). ...
Article
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Psychiatric disorders are frequently encountered in many neurological disorders, such as Alzheimer’s and Parkinson diseases along with epilepsy, migraine, essential tremors, and stroke. The most common comorbid diagnoses in neurological diseases are depression and anxiety disorders along with cognitive impairment. Whether the underlying reason is due to common neurochemical mechanisms or loss of previous functioning level, comorbidities are often overlooked. Various treatment options are available, such as pharmacological treatments, cognitive-behavioral therapy, somatic interventions, or electroconvulsive therapy. However oral antidepressant therapy may have some disadvantages, such as interaction with other medications, low tolerability due to side effects, and low efficiency. Natural compounds of plant origin are extensively researched to find a better and safer alternative treatment. Experimental studies have shown that phytochemicals such as alkaloids, terpenes, flavonoids, phenolic acids as well as lipids have significant potential in in vitro and in vivo models of psychiatric disorders. In this review, various efficacy of natural products in in vitro and in vivo studies on neuroprotective and their roles in psychiatric disorders are examined and their neuro-therapeutic potentials are shed light.
... Likewise, roseroot (Rhodiola rosea), another herbal medicine with adaptogenic properties, has shown promising antidepressant activity through its ability to modulate monoamine oxidase A [141] and cortisol levels [142,143], which are crucial in stress response and mood regulation. In a 12-week double-blind RCT comparing Rhodiola Rosea, sertraline, and placebo for major depressive disorder, sertraline showed a slight advantage in effectiveness, although roseroot demonstrated significantly milder side effects, suggesting it as a more tolerable alternative for managing depression [144]. ...
Chapter
The use of natural resources, particularly plants, for prophylactic and curative purposes dates back to ancient times and has been employed by various indigenous peoples. To survive, plants produce a variety of substances known as secondary metabolites, which are known for their distinct biological properties useful in treating diverse pathologies. Integrating empirical, traditional, and scientific knowledge has led to an increased use of natural resources as therapeutic solutions. Consequently, regulating the production processes of herbal medicines is vital to ensure their safety and efficacy. With this context, the primary aim of this chapter is to explore herbal medicines and related aspects, offering a historical perspective alongside the advances and processes involved in their extraction and production.
... The herb Rhodiola rosea (R. rosea) contains rosiridin, a monoterpene with outstanding monoamine inhibitory activity that is useful for treating depressive episodes and dementia with sudden development (Zhuang et al. 2019;Panossian and Wikman 2010;Van Diermen et al. 2009). In northeast Asian traditional medicine, the root of Rhodiola species (Crassulaceae) is utilized as antiasthmatic, bleeding treatment, and antiaging treatment (Lee et al. 2000;Linh et al. 2000). ...
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The present investigation determines the effects of rosiridin in cisplatin (CP)-induced renal toxicity in rats. The experimental animals were used and divided into four groups. Experimental rats were randomly divided into group-I normal control, group-II CP group (8 mg/kg i.p.), group-III CP + rosiridin (10 mg/kg, p.o.) and group-IV rosiridin (10 mg/kg p.o.). Various biochemical parameters, i.e., creatinine, urea, uric acid, cholesterol, blood urea nitrogen, antioxidant levels, inflammatory markers such as interleukins-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), apoptosis markers including B cell lymphoma-2 (Bcl-2), caspase-3 and histopathological investigations were evaluated. Additionally, molecular docking and dynamics were performed to assess the interaction of rosiridin with target proteins. Rosiridin significantly minimized alteration in creatinine, urea, uric acid, cholesterol, blood urea nitrogen, antioxidant levels, and inflammatory, i.e., IL-1β, IL-6, TNF-α, NF-κB, Bcl-2, and caspase-3 which CP induced in rats. The interaction of rosiridin showed a favorable docking energy. The MD simulation results showed the higher stability of the complex generated from rosiridin. The current study exhibited rosiridin having a protective effect on CP-induced renal toxicity. Graphical abstract
... Numerous monoterpenes have shown neuroprotective potential in various forms of neurodegenerative disorders [31,32]. Rosiridin, a monoterpene found in Rhodiola rosea (R. rosea), exhibits strong monoamine inhibitory activity and has been used for rapid-onset treatment of depression and dementia [33][34][35]. In northeast Asian traditional medicine, the root of Rhodiola species (Crassulaceae) is utilized as an antiasthmatic, bleeding treatment, and antiaging therapy [36,37]. ...
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Background and Objectives: Rosiridin is a monoterpene with outstanding monoamine inhibitory activity that is useful to treat depressive episodes and rapid-onset dementia. The current investigation aims to evaluate the neurologically protective impact of rosiridin, which opposes aluminum chloride (AlCl3) and causes memory dysfunction in rats. Materials and Methods: Memory impairment was developed in Wistar rats by administering AlCl3 (100 mg/kg p.o.) orally for 42 days and then supplemented with rosiridin at 10 and 20 mg/kg/p.o. Upon completion of the investigation, the behavior factor was performed utilizing the Y-maze, Morris Water Maze, and open field tests. Estimating numerous biological factors, such as nitric oxide (NO), oxidative stress (malondialdehyde MDA), acetylcholinesterase (AChE), butyrylcholinesterase levels (BuChE), antioxidants (glutathione GSH, catalase CAT, and superoxide dismutases SODs) and neurotransmitter (serotonin-5HT, dopamine-DA, acetylcholine-Ach) in the brain. Furthermore, interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF-α), brain-derived neurotrophic factor (BNDF), nuclear factor kappa B (NFᴋB), phosphatidylinositol 3-kinase (PI3K), and pAkt were assessed in the diffused brain cells. Results: The rosiridin-treated group significantly improved in terms of behavioral parameters, including in the Y-maze, Morris Water Maze, and open field tests. Further, rosiridin restored biochemical parameters, including NO, oxidative stress AChE, BuChE, antioxidants, neurotransmitters, IL-6, IL-1β, TNF-α, BNDF, NFᴋB, PI3K, and pAkt compared to AlCl3. Conclusions:The current investigation reveals that rosiridin could ameliorate the impairment of memory that AlCl3 causes in rats via improvements in behavioral and restored biochemical parameters.
... In addition, compounds such as ginsenosides, eleutheroside, cucurbitacin R diglucoside, sitoindosides, etc. are tetracyclic triterpenoids that chemically resemble the structure of corticosteroids, also known as the stress hormone (Munck et al. 1984). Furthermore, extracts from Rhodiola sp., such as rosiridin, are monoterpene glucosides that act as inhibitors of monoamine oxidases A and B (Van Diermen et al. 2009). ...
Chapter
Stress is appropriately defined as a “nonspecific response of a body to any demand”. Stress may be classified based on various factors including the type of stressor, duration of the stress response, and also on the type of influence on an individual. Upon exposure to stress and based on the type of stress, the body initiates an adaptive response that is governed by various pathological and genomic pathways. Furthermore, if exposure to stressors is prolonged for years in case of extreme stress, it may lead to a pathological state leading to chronic diseases such as cognitive deficit, accelerated aging, hypertension, and other cardiovascular diseases. Such incidences may require interventions such as nutraceuticals and medicines. Adaptogens are plant extracts that help the body adapt or adjust to chronic exposure to stress. They protect against stress-induced pathophysiological symptoms, accelerate mental functioning, and regulate homeostasis. In this chapter, we provide a basic overview of stress and how adaptogens play an excruciating role in its management. The role of selected adaptogens such as Rhodiola imbricata, Hippophae rhamnoides, Ganoderma lucidum, and Cordyceps sinensis eliciting various pharmacological actions by acting on different mechanistic pathways is described.
... The interest in modulating stress resistance processes has led to the emergence of the science of adaptation. Research has focused on understanding the mechanisms underlying the process of adaptation, elucidating what are the key variables that guide this phenomenon [3,4]. This includes screening botanicals to modulate them, aiming to avoid insufficient, disproportionate, unnecessary or erroneous stress responses. ...
Article
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This review addresses the issue of plant adaptogens, botanical products with remarkable anti-stress effects. These actions result from its ability to increase the non-specific organism's resistance process against multiple stressors (physical, chemical or biological). They are capable of exerting a normalizing effect on the human body, being both non-toxic effects and not influencing normal organic functions. Several plants with a complex phytochemical profile meet the criteria for being adaptogens. Many of them have been used in traditional medicine as tonic-vitalizing agents for centuries to treat various health conditions. This review briefly explains the organism's stress responses against stressors and the evolution of the adaptogenic concept from a historic perspective. A rational classification of adaptogens plants is formulated although it does not cover the full variability of botanical adaptogens. Nevertheless, summarizing data from two of the most important plant adaptogens, golden root (Rhodiola rosea) and Indian ginseng (Withania somnifera), are described. This includes their most deserving ethnomedicinal properties, the various families of compounds that constitute their complex phytochemical profiles, pharmacological activities along with putative mechanism of action responsible for some of their multifaceted biological actions, and the multi-therapeutic and health-promoting activities obtained from the most relevant clinical trials performed to date. Additionally, several relevant and current issues regarding the safety and toxicity of both widely used adaptogens are detailed. These include potential negative drugs interactions, putative contraindications and warnings in specific physiological statuses or health conditions. Finally, despite the overlapping activities against stress and stress-related health conditions some superior therapeutic benefits are tentatively assigned both to Withania somnifera and Rhodiola rosea taking into account the overall evidence of efficacy from pharmacological and clinical studies.
... Further studies suggest that salidroside, as one of the significant compounds, also have different pharmacological effects such as anti-aging (Gen-Xiang et al. 2010), memory improvement (Palmeri et al. 2016), anti-fatigue (Li et al. 2008), antioxidant (Zhang et al. 2007), and anti-depressant effects (Van Diermen et al. 2009). ...
Article
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Polymyxin E or colistin is an effective antibiotic against MDR Gram-negative bacteria. Due to unwanted side effects, the use of this antibiotic has been limited for a long time, but in recent years, the widespread of MDR Gram-negative bacteria infections has led to its reintroduction. Neurotoxicity and nephrotoxicity are the significant dose-limiting adverse effects of colistin. Several agents with anti-inflammatory and antioxidant properties have been used for the prevention of colistin-induced neurotoxicity. This study aims to review the preclinical studies in this field to prepare guidance for future human studies. The data was achieved by searching PubMed, Scopus, and Google Scholar databases. All eligible pre-clinical studies performed on neuroprotective agents against colistin-induced neurotoxicity, which were published up to September 2023, were included. Finally, 16 studies (ten in vitro and eight in vivo) are reviewed. Apoptosis (in 13 studies), inflammatory (in four studies), and oxidative stress (in 14 studies) pathways are the most commonly reported pathways involved in colistin-induced neurotoxicity. The assessed compounds include non-herbal (e.g., ascorbic acid, rapamycin, and minocycline) and herbal (e.g., curcumin, rutin, baicalein, salidroside, and ginsenoside) agents. Besides these compounds, some other measures like transplantation of mitochondria and the use of nerve growth factor and mesenchymal stem cells could be motivating subjects for future research. Based on the data from experimental (in vitro and animal) studies, a combination of colistin with neuroprotective agents could prevent or decrease colistin-induced neurotoxicity. However, well-designed randomized clinical trials and human studies are essential for demonstrating efficacy.
... After the first evaluation of highly hydrophilic salidroside (cLogP = −0.29) and its aglycone tyrosol as hMAO-B inhibitors [79], other authors attempted to obtain chemical modifications involving the phenolic moiety and the 3'-OH and 6'-OH of the sugar portion to improve the lipophilicity and optimal BBB permeation ( Figure 12c). The compounds were first assessed as cytoprotectants in PC12 cells and then salidroside and its benzoyl ester derivative (cLogP = 1.85) were further tested as hMAO-B inhibitors (IC 50 on hMAO-B were 0.81 and 0.08 µM and K I were 0.92 and 0.041 µM, respectively). ...
Article
Introduction: Over the past five years, we have witnessed intense research activity about the biological potential of natural products (NPs) as human monoamine oxidase B (MAO-B) inhibitors. Despite the promising inhibitory activity, natural compounds are often characterized by pharmacokinetic limitations such as poor aqueous solubility, extensive metabolism, and low bioavailability. Areas covered: This review provides an overview of the current landscape NPs as selective hMAO-B inhibitors and highlights their use as a starting scaffold to design (semi)synthetic derivatives to overcome the therapeutic (pharmacodynamic and pharmacokinetic) limitations of NPs and to obtain more robust structure-activity relationships (SARs) for each scaffold. Expert opinion: All the natural scaffolds herein presented displayed a broad chemical diversity. The knowledge of their biological activity as inhibitors of hMAO-B enzyme allows the positive correlations associated with the consumption of specific food or the possible herb-drug interactions and suggests to the Medicinal Chemists how to address chemical functionalization to obtain more potent and selective compounds.
... The greatest similarity in the identified chemical compounds is found in representatives of the genera Mentha, Vaccinium, Rosmarinus, Astragali, and Eucalyptus. In addition, Rhodioloside C (monoterpene glycoside), previously described in Rhodiola rosea, was found in leaf extracts [15][16][17] and Rhodiola crenulata [18]. ...
Article
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Dracocephalum jacutense Peschkova is a rare and endangered species of the genus Dracocephalum of the Lamiaceae family. The species was first described in 1997 and listed in the Red Data Book of Yakutia. Significant differences in the multicomponent composition of extracts from D. jacutense collected in the natural environment and successfully introduced in the Botanical Garden of Yakutsk were identified by a team of authors earlier in a large study. In this work, we studied the chemical composition of the leaves, stem, and inflorescences of D. jacutense using the tandem mass spectrometry method. Only three cenopopulations of D. jacutense were found by us in the territory of the early habitat—in the vicinity of the village of Sangar, Kobyaysky district of Yakutia. The aboveground phytomass of the plant was collected, processed and dried as separate parts of the plant: inflorescences, stem and leaves. Firstly, a total of 128 compounds, 70% of which are polyphenols, were tentatively identified in extracts of D. jacutense. These polyphenol compounds were classified as 32 flavones, 12 flavonols, 6 flavan-3-ols, 7 flavanones, 17 phenolic acids, 2 lignans, 1 dihydrochalcone, 4 coumarins, and 8 anthocyanidins. Other chemical groups were presented as carotenoids, omega-3-fatty acids, omega-5-fatty acids, amino acids, purines, alkaloids, and sterols. The inflorescences are the richest in polyphenols (73 polyphenolic compounds were identified), while 33 and 22 polyphenols were found in the leaves and stems, respectively. A high level of identity for polyphenolic compounds in different parts of the plant is noted for flavanones (80%), followed by flavonols (25%), phenolic acids (15%), and flavones (13%). Furthermore, 78 compounds were identified for the first time in representatives of the genus Dracocephalum, including 50 polyphenolic compounds and 28 compounds of other chemical groups. The obtained results testify to the unique composition of polyphenolic compounds in different parts of D. jacutense.
... 137 The psychopharmacological mechanisms of RL in the depression-like behavior model were mainly related to the inhibition of monoamine oxidase A, the modulation of the content of 5-HT, and the cell proliferation and number of neurons in depressed rats and mice. 138,139 Salidroside (SA), the primary bioactive compound in RL, exerts antidepressant activity in olfactory bulbectomized rats, which may be related to the regulation of the anti-inflammatory pathway and HPA axis activity. 140 In mice with LPS-induced depression-like behavior, SA treatment significantly attenuated LPS-induced inflammation, reduced NE and 5-HT levels in the prefrontal cortex, and increased the expression levels of BNDF and TrkB within the BDNF/TrkB signaling pathway. ...
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Depression, a mental illness that is receiving increasing attention, is caused by multiple factors and genes and adversely affects social life and health. Several hypotheses have been proposed to clarify the pathogenesis of depression, and various synthetic antidepressants have been introduced to treat patients with depression. However, these drugs are effective only in a proportion of patients and fail to achieve complete remission. Recently, herbal medicines have received much attention as alternative treatments for depression because of their fewer side effects and lower costs. In this review, we have mainly focused on the herbal medicines that have been proven in clinical studies (especially randomized controlled trials and preclinical studies) to have antidepressant effects; we also describe the potential mechanisms of the antidepressant effects of those herbal medicines; the cellular and animal model of depression; and the development of novel drug delivery systems for herbal antidepressants. Finally, we objectively elaborate on the challenges of using herbal medicines as antidepressants and describe the benefits, adverse effects, and toxicity of these medicines.
... rosea). This plant is also called golden root or arctic root [30], is mainstream among herbal medicines, and is commonly seen at higher altitudes in the arctic and in mountain ranges throughout Europe and Asia [31]. The medicinal application of R.rosea includes its ability to control psychological stress and mental strength, change the neurotransmitter levels and Central Nervous System (CNS) activity, resistance to high altitude sickness, treat fatigue [32][33][34][35][36], and also act as an anti-depressant and anti-inflammatory drug [37]. ...
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The COVID-19 pandemic outbreak demands the designing of potential drugs as there is no specific treatment available. Thanks to their safety and effectiveness, phytochemicals have been used to treat various diseases, including antiviral therapeutics. Molecular docking is a simple, quick, and effective way to screen a variety of molecules for structure-based drug design. Here, we investigate molecular docking experiments on compounds present in plant species, Cocculus hirsutus and Rhodiola rosea and show their potential for the treatment of COVID-19. Almost all the components showed higher binding affinity than the built-in ligand, and those with significantly higher binding affinity were explored further. Molecular mechanics-based generalized born surface area calculations were used to re-rank the top candidates, rhodionidin and cocsoline, and their stability in association with viral protease was confirmed. Density functional theory was used for detailed investigations of the geometries, and electrical properties of rhodionidin and cocsoline. Using the frontier molecular orbitals method, the charge transfer within the molecule was calculated. Chemical reactivity and intermolecular interactions were studied using molecular electrostatic potential maps. These in silico discoveries will simulate the identification of powerful COVID-19 inhibitors, and similar research is likely to make a significant contribution to antiviral drug discovery. Supplementary information: The online version contains supplementary material available at 10.1007/s11224-022-01982-4.
... The well-known species among them is Rhodiola rosea L.(R. rosea). This plant is also called golden root or arctic root [30], is mainstream among herbal medicines and is commonly seen at higher altitudes in the arctic and in mountain ranges throughout Europe and Asia [31]. The medicinal application of R.rosea includes its ability to control psychological stress and mental strength, change the neurotransmitter levels and central nervous system (CNS) activity, resistance to high altitude sickness, treat fatigue [32][33][34][35][36], and also act as an anti-depressant and anti-in ammatory drug [37]. ...
Preprint
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The COVID-19 pandemic outbreak demands the designing of potential drugs as there is no specific treatment available. Thanks to their safety and effectiveness, phytochemicals have been used to treat various diseases, including antiviral therapeutics. Molecular docking is a simple, quick, and effective way to screen a variety of molecules for structure-based drug design. Here, we investigate molecular docking experiments on compounds present in plant species, C.hirsutus and R.rosea and show their potential for the treatment of COVID-19. Almost all the components showed higher binding energies than the built-in ligand, and those with significantly higher binding energies were explored further. Molecular mechanics-based generalized born surface area calculations were used to re-rank the top candidates, rhodionidin and cocsoline, and their stability in association with viral protease was confirmed. Density functional theory was used for detailed investigations of the geometries, electrical properties, and molecule electrostatic potential of rhodionidin and cocsoline. Using the frontier molecular orbitals method, the charge transfer within the molecule was calculated. Chemical reactivity and intermolecular interactions were studied using molecular electrostatic potential maps. These in silico discoveries will simulate the identification of powerful COVID-19 inhibitors, and similar research is likely to make a significant contribution to antiviral drug discovery.
... Therapeutic properties of RR are related to flavonoids, phenylpropanoids, and organic acids in its roots and rhizomes. RR has also numerous beneficial pharmacological activities including anti-inflammatory, antioxidant, antidepressive, antifibrotic, antiallergic, anticancer and antiapoptotic activities [7][8][9][10][11] . This is the first study to investigate the protective effects of RR in peptic ulcer disease. ...
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Objective: The objective of the present study was to evaluate the effects of Rhodiola rosea in the indomethacin-induced ulcer model in rats and to clarify the underlying mechanisms of action. Methods: Rats in treatment groups were treated with Rhodiola rosea (RR) 14 days. Peptic ulcer was induced by indomethacin (IND) injection (100 mg/kg, p.o.). The groups (n = 6) were designed as; Group I (control); Group II (IND): After 24h of food starvation, rats were given only 100 mg/kg IND by oral gavage to induce gastric mucosal injury. Group III (ESO): Rats were pretreated with 20 mg/kg of ESO for 14 consecutive days by oral gavage. Group IV (RR): Rats were pretreated with 500 mg/kg RR for 14 consecutive days with oral gavage. Results: Rhodiola rosea effectively alleviated indomethacin-induced ulcer via reduction in oxidative stress (decreased MDA and increased SOD, and GSH). Moreover, Rhodiola rosea alleviated indomethacin-induced damage by regulating expressions of COX enzymes, prostaglandin E2, proliferating cell nuclear antigen (PCNA), cell proliferation, apoptosis and regulated the NF-κB signaling pathway. Rhodiola rosea also attenuated inflammatory injury by suppressing TNF-𝛼𝛼, IL1β, and NF-κB. The caspase-3 expression was also down-regulated in stomach tissues. Conclusions: In conclusion, Rhodiola rosea protected the gastric mucosa from harmful effects of indomethacin and as a natural medicinal herb, Rhodiola rosea might be a potential therapeutic agent for preventing and treating indomethacininduced gastric damage.
... They attributed this antidepressant effect to terpene and monoterpenoid compounds such as beta-pinene, beta-thujone, limonene, and linalool (Rabadia et al., 2013). These compounds are the main ingredients of C. zeylanicum (Ranasinghe et al., 2013;Rao and Gan, 2014) which have anti-depressant properties mediated by inhibiting monoamine oxidase A and B (Van Diermen et al., 2009). Also, C. zeylanicum, with its beta-pinene, can increase the activity of the animal by increasing the level of dopamine and reducing the activity of monoamine oxidase (Li et al., 2018). ...
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... They attributed this antidepressant effect to terpene and monoterpenoid compounds such as beta-pinene, beta-thujone, limonene, and linalool (Rabadia et al., 2013). These compounds are the main ingredients of C. zeylanicum (Ranasinghe et al., 2013;Rao and Gan, 2014) which have anti-depressant properties mediated by inhibiting monoamine oxidase A and B (Van Diermen et al., 2009). Also, C. zeylanicum, with its beta-pinene, can increase the activity of the animal by increasing the level of dopamine and reducing the activity of monoamine oxidase (Li et al., 2018). ...
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Objective: Depression is one of the most common mood disorders. Considering the evidence on the effect of Cinnamomum on mood disorders, this study investigatedthe effect of hydroalcoholic extract of Cinnamomum (HEC) in an animal model of depression. Materials and methods: Thirty-two male rats were selected and divided into four groups (n=8) including: control, depressed, and depressed treated with200 and 400 mg/kg HEC. Depression induction protocol was conducted in all groups except for the control group. Sucrose preference test (SPT) and forced swimming test (FST) were done to analyze the depression score. After four weeks, the animals brain cortex was removed and BDNF protein and tyrosine receptor kinase B (TrkB) gene expression levels were determined by ELISA and Real Time PCR, respectively. Results: The results of this study showed that 400 mg/kg of HEC increased the tendency to drink the sucrose solution. Furthermore, immobility time significantly increased in the depressed group compared to the control group while it was attenuated by administration of 400 mg/kg extract on the 28th day versus the depressed group. Also the extract at both doses increased swimming time compared to the depressed group. In addition, an increase in the BDNF protein and TrkB gene expression levels was observed in the prefrontal cortex of the treatment groups. Conclusion: We found that HEC ameliorated depression symptoms in rats and these effects were probably due to an increase in BDNF proteins and its receptor, TrkB, gene expressions in the prefrontal cortex.
... Ekstrakt z surowca hamuje także aktywność monoaminooksydazy typu A i B (MAO-A i MAO-B) oraz katecholo-O-metylotrasferazy (COMT)enzymów katalizujących oksydacyjną deaminację neuroprzekaźników monoaminowych. Biorąc pod uwagę fakt, że MAO-A odgrywa istotną rolę w regulacji nastroju, zaś MAO-B w rozwoju chorób neurodegeneracyjnych można uznać, że R. rosea wykazuje działanie przeciwdepresyjne, jednocześnie wykazując aktywność neuroprotekcyjną i prokognitywną [79]. ...
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Depression, a neurological disorder, is a universally common and debilitating illness where social and economic issues could also become one of its etiologic factors. From a global perspective, it is the fourth leading cause of long-term disability in human beings. For centuries, natural products have proven their true potential to combat various diseases and disorders, including depression and its associated ailments. Translational informatics applies informatics models at molecular, imaging, individual, and population levels to promote the translation of basic research to clinical applications. The present review summarizes natural-antidepressant-based translational informatics studies and addresses challenges and opportunities for future research in the field.
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Pharmacological treatment of Parkinson’s disease consists of a combined chemotherapy that mostly relies on levodopa (L-DOPA) administration together with inhibitors of dopa-decarboxylase (DDC), monoamine oxidase (MAO) and catechol-methyltransferase (COMT). Identification of inhibitors specifically targeting these enzymes is still a significative part of the development of new alternative antiparkinsonian drugs. Most of the available methods use measurement of enzymatic reactions through radioactive labeling, antibody-recognized products or coupled enzymatic assays. Mass spectrometry (MS) represents an interesting alternative approach as it allows direct and specific detection and quantification of enzymatic reactions. We describe the development of a simple, reliable, label-free assay based on high-resolution mass spectrometry (HRMS) for the detection and relative quantification of three different enzymatic reactions using non-isolated enzymes. The assay was applied both to reference drugs and plant crude extracts. This method can be used to detect hits in extracts libraries as well as determine relative IC50 of inhibitors.
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Consideration and improvement for anxiety and depression are important during global pandemic diseases. Appropriate healthcare can be obtained by paying more attention to traditional medicinal sciences. The adverse effects of stress with its various symptoms can be managed by introducing plants that boost mental health. The most relevant psychological reactions in the general population related to global pandemic are pervasice anxiety, frustration and boredom, aspecific and uncontrolled fear, disabling loneliness, significant lifestyle changes, and psychiatric conditions. Ginseng, chamomile, passionflower, herbal tea, lavender, saffron, kava, rose, cardamom, Chinese date and some chief formula like yokukansan, Dan-zhi-xiao-yao-san, so-ochim-tang-gamiband, and saikokaryukotsuboreito are notable herbal treatments for mental health problems. The most common medicinal plants which have been used in Iran for the cure of stress and anxiety are Viper,s-buglosses, Dracocephalum, valerian, chamomile, common hop, Hawhorns, and Lavender. Medicinal plants and herbs can be used for treatment and alleviating negative effects of stress, anger and depression during the global pandemic.
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Monoamine oxidase (MAO) is capable of catalysing the oxidative deamination of amines and neurotransmitters. MAO plays a pivotal role in maintaining neurotransmitters linked to neurological disorders viz. Alzheimer's disease (AD), Parkinson's disease (PD) etc. Therefore, inhibition of MAO can be implicated to the cure of such diseases. Synthetic MAO inhibitors are known to inhibit MAO activity. However, there are safety issues with synthetic MAO inhibitors and many of their effects are non-selective and irreversible. Contrasting synthetic drugs, plant-derived natural products have been popularized globally owing to their extensive acceptability and applicability, therapeutic potency and minimum side effects which potentiated the possibility of developing reversible, promising MAO inhibitors based on natural products. The present review comprehensively elucidates plant -derived natural reversible MAO inhibitors using the literature from the popular databases such as Google Scholar, Scopus, PubMed and Web of Science. This literature review reports approximately 51 plants that have been evaluated for MAO inhibitory activity. In addition, 93 plant-derived natural compounds were retrieved as MAO inhibitors. Majority of these investigations predominantly utilized an in vitro approach to evaluate the MAO inhibitors in relation to the developing treatments of related neurological diseases. However, in vivo studies and clinical trials are still lacking in evaluating the botanical-based MAO inhibitors. The aim of this review is to retrieve the recent literature to explore the in vitro and in vivo studies of plant-based natural products as MAO inhibitors, their structure-activity relationship and relevant molecular docking analyses and their roles in the emerging therapy against disorders like AD, and PD. Further, the review also discusses the shortcomings in the existing research in order to generate more coordinated and focused research in future.
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Background: Angina pectoris is a kind of cardiovascular disease, which is caused by epicardial stenosis, microvascular dysfunction, dynamic stenosis area contraction or more comprehensive factors, eventually leading to Coronary artery disease. Rhodiola wallichiana var. cholaensis, which is one of the most well-known Traditional Chinese Medicine, is widely used to treat angina pectoris. However, the possible underlying mechanisms remain to be elucidated. Methods: In this study, systematic and comprehensive network pharmacology and molecular docking were utilized for the first time to reveal the potential pharmacological mechanisms of RW on AP. Firstly, the relative compounds were obtained by mining literature and potential targets of these compounds by target predicting were collected. Then, We built the AP target database using the DigSee and GeneCards Database. Based on the data, GO and KEGG pathway enrichment analysis, protein-protein interaction (PPI) analysis were performed and screen the hub targets by topology. Furthermore, evaluation of the binding potential of key targets and compounds through molecular docking. Results: The results indicate that 218 known RW therapeutic targets were selected. By systematic analysis, identified 9 hub targets (VEGFA, GAPDH, TP53, AKT1, CASP3, STAT3, TNF, MAPK1 and JUN) mainly involved in the complex treating effects associated with the protection of vascular endothelium, as well as the regulation of glucose metabolism, cellular processes, inflammatory responses, and cellular signal transduction. Conclusion: The results of this study preliminarily explain the potential targets and signaling pathways of RW in AP therapy and lay a good foundation for further experimental studies and clinical trials.
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Background Depression affects people feeling to be anxious, worried, and restless. They also lose interest in activities, concentrating and appetite, they finally may attempt suicide. Depression is the second chronic disease, as a source of the global burden of disease, after heart disease. Its prevalence elevated seven times during the COVID-19. Aim The current study was designed to evaluate camphor neuroprotective role against rats’ ciprofloxacin-induced depression. Materials and methods Depression was induced by administration of ciprofloxacin (50 mg/kg; orally) for 21 days. Wister albino male rats were divided into five groups. Group I (normal control): rats were given normal saline. Group II: rats received camphor (10 mg/kg; i.p.) for 21 days. Group III (depression control): rats received ciprofloxacin only. Groups IV and V: rats received camphor (5 and 10 mg/kg; i.p.) for 21 days concurrent with ciprofloxacin. Behavior tests as forced swimming test, activity cage, and rotarod were estimated. Oxidative stress and antioxidant biomarkers as malondialdehyde (MDA), nitric oxide (NO), catalase, and nuclear factor erythroid 2-related factor 2 (Nrf-2) besides inflammatory biomarkers as Toll-like receptor 4 (TLR4) and tumor necrosis factor alpha (TNF-α) as well as neurotransmitters were determined. Finally, histopathological examination was done. Results Camphor increased catalase and Nrf-2 activities, decreased NO, MDA, TNF-α, TLR4 serum levels, and elevating brain contents of serotonin, dopamine, gamma-amino butyric acid (GABA) and P190-RHO GTP protein with normal neuronal cells of the frontal cortex. Conclusion Camphor has neuroprotective effect via modulation of Nrf-2 and TLR4 against ciprofloxacin-induced depression in rats.
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Rhodiola rosea L., also known as "golden root" or "roseroot" belongs to the plant family Crassulaceae.1 R. rosea grows primarily in dry sandy ground at high altitudes in the arctic areas of Europe and Asia.2 The plant reaches a height of 12 to 30 inches (70cm) and produces yellow blossoms. It is a perennial with a thick rhizome, fragrant when cut. The Greek physician, Dioscorides, first recorded medicinal applications of rodia riza in 77 C.E. in De Materia Medica.3 Linnaeus renamed it Rhodiola rosea, referring to the rose-like attar (fragrance) of the fresh cut rootstock.4 For centuries, R. rosea has been used in the traditional medicine of Russia, Scandinavia, and other countries. Between 1725 and 1960, various medicinal applications of R. rosea appeared in the scientific literature of Sweden, Norway, France, Germany, the Soviet Union, and Iceland.2,4-12 Since 1960, more than 180 pharmacological, phytochemical, and clinical studies have been published. Although R. rosea has been extensively studied as an adaptogen with various health-promoting effects, its properties remain largely unknown in the West. In part this may be due to the fact that the bulk of research has been published in Slavic and Scandinavian languages. This review provides an introduction to some of the traditional uses of R. rosea, its phytochemistry, scientific studies exploring its diverse physiological effects, and its current and future medical applications.
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The objective was to investigate the stimulating and normalizing effect of the adaptogen Rhodiola rosea extract SHR-5 in foreign students during a stressful examination period. The study was performed as a double-blind, randomized and placebo-controlled with low repeated dose regime. The study drug and the placebo were taken for 20 days by the students during an examination period. The physical and mental performance were assessed before and after the period, based on objective as well as on subjective evaluation. The most significant improvement in the SHR-5 group was seen in physical fitness, mental fatigue and neuro-motoric tests (p <0.01). The self-assessment of the general well-being was also significantly (p < 0.05) better in the verum group. No significance was seen in the correction of text tests or a neuro-muscular tapping test. The overall conclusion is that the study drug gave significant results compared to the placebo group but that the dose level probably was suboptimal.
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An HPLC method permitting the first simultaneous detection of 5 marker compounds (salidroside, rosarin, rosavin, rosin, rosiridin) of R. rosea was developed. A separation was achieved within 27 min by using C-18 column material, a phosphate buffer/acetonitrile gradient system and at a separation temperature of 60 degrees C. All five compounds could be detected at concentrations as low as 0.62 microg/ml and were clearly assignable in R. rosea plant material and commercial products. Therefore, this quantitative and qualitative applicability of the method offers efficient and reliable means for the evaluation of R. rosea and products thereof.
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The methanolic extract of the underground part of Rhodiola sachalinensis was found to show inhibitory activity on prolyl endopeptidase (PEP, EC. 3.4.21.26), an enzyme that plays a role in the metabolism of proline-containing neuropeptidase which is recognized to be involved in learning and memory. From the MeOH extract, five new monoterpenoids named sachalinols A (24), B (25) and C (26) and sachalinosides A (23) and B (27) were isolated, together with twenty-two known compounds, gallic acid (1), trans-p-hydroxycinnamic acid (2), p-tyrosol (3), salidroside (4), 6n-O-galloylsalidroside (5), benzyl beta-D-glucopyranoside (6), 2-phenylethyl beta-D-glucopyranoside (7), trans-cinnamyl beta-D-glucopyranoside (8), rosarin (9), rhodiocyanoside A (10), lotaustralin (11), octyl beta-D-glucopyranoside (12), 1,2,3,6-tetra-O-galloyl-beta-D-glucose (13), 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (14), kaempferol (15), kaempferol 3-O-beta-D-xylofuranosyl(1-->2)-beta-D-glucopyranoside (16), kaempferol 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranoside (17), rhodionin (18), rhodiosin (19), (-)-epigallocatechin (20), 3-O-galloylepigallocatechin-(4-->8)-epigallocatechin 3-O-gallate (21) and rosiridin (22). Among these, nineteen compounds other than 3, 4 and 9 have been isolated for the first time from R. sachalinensis, and six (6, 8, 13, 16, 17, 20) are isolated from Rhodiola plants for the first time. Among them, six compounds (13, 14, 18, 19, 21, 22) showed noncompetitive inhibition against Flavobacterium PEP, with an IC50 of 0.025, 0.17, 22, 41, 0.44 and 84 microM, respectively.
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Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors. The beneficial effects of multi-dose administration of adaptogens are mainly associated with the hypothalamic-pituitary-adrenal (HPA) axis, a part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation. In contrast, the single dose application of adaptogens is important in situations that require a rapid response to tension or to a stressful situation. In this case, the effects of the adaptogens are associated with another part of the stress-system, namely, the sympatho-adrenal-system (SAS), that provides a rapid response mechanism mainly to control the acute reaction of the organism to a stressor. This review focuses primarily on the SAS-mediated stimulating effects of single doses of adaptogens derived from Rhodiola rosea, Schizandra chinensis and Eleutherococcus senticosus. The use of these drugs typically generates no side effects, unlike traditional stimulants that possess addiction, tolerance and abuse potential, produce a negative effect on sleep structure, and cause rebound hypersomnolence or 'come down' effects. Furthermore, single administration of these adaptogens effectively increases mental performance and physical working capacity in humans. R. rosea is the most active of the three plant adaptogens producing, within 30 min of administration, a stimulating effect that continues for at least 4-6 h. The active principles of the three plants that exhibit single dose stimulating effects are glycosides of phenylpropane- and phenylethane-based phenolic compounds such as salidroside, rosavin, syringin and triandrin, the latter being the most active.
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The objective of this study was to assess the efficacy and safety of standardized extract SHR-5 of rhizomes of Rhodiola rosea L. in patients suffering from a current episode of mild/moderate depression. The phase III clinical trial was carried out as a randomized double-blind placebo-controlled study with parallel groups over 6 weeks. Participants, males and females aged 18-70 years, were selected according to DSM-IV diagnostic criteria for depression, the severity of which was determined by scores gained in Beck Depression Inventory and Hamilton Rating Scale for Depression (HAMD) questionnaires. Patients with initial HAMD scores between 21 and 31 were randomized into three groups, one of which (group A: 31 patients) received two tablets daily of SHR-5 (340 mg/day), a second (group B: 29 patients) received two tablets twice per day of SHR-5 (680 mg/day), and a third (group C: 29 patients) received two placebo tablets daily. The efficacy of SHR-5 extract with respect to depressive complaints was assessed on days 0 and 42 of the study period from total and specific subgroup HAMD scores. For individuals in groups A and B, overall depression, together with insomnia, emotional instability and somatization, but not self-esteem, improved significantly following medication, whilst the placebo group did not show such improvements. No serious side-effects were reported in any of the groups A-C. It is concluded that the standardized extract SHR-5 shows anti-depressive potency in patients with mild to moderate depression when administered in dosages of either 340 or 680 mg/day over a 6-week period.
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From the whole plant of Boschniakia rossica (Cham. et Schlech.) Fedtsch. et Flerov., a new phenylpropanoid glycoside (2) was isolated together with fourteen known compounds which include two phenylpropanoid glycosides [rossicaside B (1) and rossicaside A (3)], triandrin (4), boschniakinic acid (5), two iridoid glucosides [boschnaloside (6), 8-epideoxyloganic acid (7)], three triterpenoids [3-epioleanolic acid (8), 3-epiacetyloleanolic acid (9), oleanolic acid (10)], β-sitosterol (11), and four iridoid aglycones [1,10-bisdeoxy-7,8-dihydrogenipin (12), 7-methyl-octahydro-cyclopenta[c]pyran-4- carboxylic acid (13), (1R) and (1S) 1-O-methyl-8-epideoxyloganic acid aglycone (14,15)].
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The Rosavin framework could be constructed with either phenylboronic acids, the protected arabinopyranosyl bromide 4 or the protected xylopyranosyl bromide 5, along with allyl O-β-d-glucopyranoside 7 that could be easily prepared based on direct β-glucosidation between allyl alcohol and d-glucose using the immobilized β-glucosidase (EC 3.2.1.21). The key reaction was the Pd(II)-catalyzed Mizoroki-Heck type reaction between allyl β-d-glucopyranoside congeners 9 or 10 and arylboronic acids. Deprotection of the coupling products afforded synthetic Rosavin 1, 4-methoxycinnamyl 6-O-(α-l-arabinopyranosyl)-β-d-glucopyranoside 2, and cinnamyl 6-O-(β-d-xylopyranosyl)-β-d-glucopyranoside 3, which were identical with the natural products in respect to the specific rotation and spectral data.
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Rhodiola rosea L., or 'golden root', is a popular plant in traditional medicine in Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress. Due to these therapeutic prop-erties, R. rosea is considered to be one of the most active adaptogenic drugs. To confirm and extend results obtained in the few preclinical and clinical studies available in English language journals, the purpose of the present study was to re-investigate the effects produced by a single oral administration of an R. rosea hydroalcohol extract (containing 3% rosavin and 1% salidroside) on the central nervous system in mice. The extract was tested on antidepressant, adaptogenic, anxiolytic, nociceptive and locomotor activities at doses of 10, 15 and 20 mg/kg, using predictive behavioural tests and animal models. The results show that this R. rosea extract significantly, but not dose-dependently, induced antidepressant-like, adaptogenic, anxiolytic-like and stimulating effects in mice. This study thus provides evidence of the efficacy of R. rosea extracts after a single administration, and confirms many preclinical and clinical studies indicating the adaptogenic and stimulating effects of such R. rosea extracts. Moreover, antidepressant-like and anxiolytic-like activities of R. rosea were shown in mice for the first time.
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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.
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Monoamine oxidase type B (MAO-B) activity and free radicals are elevated in certain neurological diseases. Four natural flavonoids, quercitrin, isoquercitrin, rutin, and quercetin, were isolated for the first time from the leaves of Melastoma candidum D. Don. They exhibited an inhibitory effect on MAO-B. These potent flavonoids were purified using bioassay-guided fractionation and were separated by Diaion, Sephadex LH-20, and MCI CHP20P columns. The IC50 values of the four potent flavonoids, quercitrin, isoquercitrin, rutin, and quercetin on monoamine oxidase were 19.06, 11.64, 3.89, and 10.89 μM and enzyme kinetics analysis revealed apparent inhibition constants (Ki) of 21.01, 2.72, 1.83, and 7.95 μM, respectively, on the substrate, benzylamine. The four potent compounds also exhibited hydroxyl radical scavenging activity as determined using a spin trapping electron spin resonance method. This suggests that the four flavonoids from M. candidum possess both MAO-B inhibitory and free radical scavenging activities. These important properties may be used for preventing some neurodegenerative diseases in the future. Keywords: Melastoma candidum; monoamine oxidase B; quercitrin; isoquercitrin; quercetin; rutin; hydroxyl radical scavenging
Article
Metabolites, previously designated Gl 3, Gl 5, and Gl 6, from embryos of the American ash (Fraxinus americana) were examined by spectral methods, degradation achieved by methanolysis and conversion to acetates. Gl 6 is identified as nüzhenide. Acetylation of Gl 3 and Gl 5 gives 1H NMR determined undecaacetate and octaacetate, respectively, thus providing evidence for the number of free hydroxyl groups and furnishing material suitable for molecular weight determinations by vapor-phase osmometry. Evidence for the identity and sequence of the various units was obtained, among other methods, through methanolysis, Gl 3 giving nüzhenide and oleoside 7-methyl ester and Gl 5 giving ligstroside and oleoside 7-methyl ester. Gl 3 contains one unit of 2-(4-hydroxyphenyl)ethanol (Tyo), three units of glucose [all as 1-β-D-glucopyranosides (β-D-Glc)], and two of oleoside aglucon (β-Olo) in the sequence: β-D-Glcl-1β-Olo7-6β-D-Glcl-1Tyo6-7β-Olol-1β-D-Glc. Gl 5 contains the same components as Gl 3 but one less glucose unit in the sequence β-D-Glcl-1β-Olo7-1Tyo6-7β-Olol-1β-D-Glc. 13C NMR proves to be an especially valuable tool in determining the sequence of units in the intact metabolites.
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The antidepressant activity of some phytopreparations and phenylpropanoids was studied in white rats, which were subjected to the desperation test and neuropharmacological tests based on the antagonist activity with respect to reserpine, clofelin, and L-DOPA. The most pronounced effect was exhibited by the extract of Eleutherococcus senticosus, which produced a 56.4% decrease in the immobilization period in rats that was comparable with, albeit somewhat lower than the effect of amitriptyline (73.5%). The antidepressant effects of other phytopreparations decreased in the following order: Rhodiola rosea (53.8%), Echinacea purpurea (49%), and Schizandra chinensis (29.8%). Among phenylpropanoids, the maximum antidepressant effects were produced by syringin and rosavin (49.7% and 29.5%, respectively). The most pronounced antagonism with respect to reserpine was also observed for syringin. The tinctures of Echinacea purpurea and Schizandra chinensis, as well as phenylpropanoid triandrin produced the maximum antidepressant effect in the clofelin-induced depression test. An increase in the stimulating action of L-DOPA was observed upon the administration of rosavin and the tinctures of Schizandra chinensis and Echinacea purpurea.
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Two new antiallergic cyanoglycosides named rhodiocyanosides A and B were isolated from the Chinese natural medicine "Si Lie Hong Jing Tian" (Shiretsukoukeiten in Japanese), the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey., together with two new glycosides, octyl alpha-L-arabinopyranosyl(1-6)-beta-D-glucopyranoside and gossypetin 7-O-beta-D-glucopyranosyl(1-3)-alpha-L-rhamnopyranoside. Their chemical structures were determined on the basis of chemical and physicochemical evidence. Rhodiocyanosides A and B exhibited inhibitory activity on the histamine release from rat peritoneal exudate cells sensitized with anti-DNP IgE. In addition, rhodiocyanoside A was found to inhibit the PCA reaction in rats.
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The clinically tested reversible inhibitors of monoamine oxidase A (RIMAs) include brofaromine, moclobemide and toloxatone. Moclobemide has shown unequivocal antidepressant activity against serious depressive illness in 4 placebo-controlled double-blind trials. It has been compared with amitriptyline, imipramine, clomipramine, desipramine, maprotiline, fluoxetine, fluvoxamine, tranylcypromine, toloxatone, mianserin and amineptine in the treatment of depressive disorders. Meta-analysis showed convincing evidence of moclobemide efficacy, comparable with the most potent antidepressants available. The efficacy of moclobemide has been demonstrated in psychotic and non-psychotic depression, in depression with and without melancholia, in endogenous depression (both unipolar and bipolar), in retarded depression and in agitated depression. The efficacy of moclobemide, allied to the unusually benign side effect profile, has led to exploration of its use in other disorders. Two small studies have given encouraging results in the treatment of attention-deficit hyperactivity disorder. Large placebo-controlled studies have shown the activity of moclobemide in the depression that accompanies dementia (such as senile dementia of Alzheimer type). The results also suggested that, in this patient population, cognitive ability improved in parallel. Social phobia has also been shown to improve on treatment with either moclobemide or brofaromine. Clinical trials are in progress on the effect of moclobemide in chronic fatigue syndrome. Moreover, there are encouraging results with the use of brofaromine and moclobemide in panic disorder. Other disorders in which treatment with RIMA is of interest include agoraphobia, bulimia, borderline personality disorder, post-traumatic stress disorder, compulsive hair pulling (trichotillomania), dysmorphophobia, kleptomania as well as various anxiety syndromes.
Article
The aetiology and pathogenesis of Alzheimer's disease are currently poorly understood, but symptomatic disease is associated with amyloid plaques, neurofibrillary tangles, neuronal loss and numerous alterations of neurotransmitter systems in the CNS. Monoamine oxidase type B is known to be increased in Alzheimer diseased brains. The distribution and abundance of catalytic sites for monoamine oxidases A and B in post mortem human brains of 11 Alzheimer disease cases and five age-matched controls were investigated by quantitative enzyme radioautography. Using tritiated monoamine oxidase inhibitors (Ro41-1049 and lazabemide)--as high affinity substrates selective for monoamine oxidases A and B, respectively--it was found that monoamine oxidase B activity increased up to three-fold exclusively in temporal, parietal and frontal cortices of Alzheimer disease cases compared with controls. This increase was restricted to discrete patches (approximately 185 microns in diameter) which occupied approximately 12% of the cortical areas examined. In other brain regions (hippocampal formation > caudate-putamen > cerebellum), patches of [3H]lazabemide-enriched binding were less abundant. [3H]Ro41-1049 binding (i.e. monoamine oxidase A) was unchanged in all tissues of diseased versus control brains. The monoamine oxidase B-enriched patches in all cortical regions correlated, in their distribution and frequency, with glial fibrillary acidic protein-immunoreactive clusters of astrocytes. Diffuse and mature beta-amyloid-immunoreactive senile plaques as well as patches of high density binding of [3H]PK-11195--a high-affinity ligand for peripheral-type (mitochondrial) benzodiazepine binding sites in microglia/macrophages--were found throughout Alzheimer diseased cortices. The up-regulation of monoamine oxidase B in plaque-associated astrocytes in Alzheimer's disease--in analogy to its proposed role in neurodegenerative disorders such as Parkinson's disease--might, indirectly, be a potential source of cytotoxic free radicals. Lazabemide, a selective reversible monoamine oxidase B inhibitor, is currently under clinical evaluation for the treatment of Parkinson's and Alzheimer's diseases. We conclude that enzyme radioautography with [3H]lazabemide is a reliable high resolution assay for plaque-associated astroglioses in Alzheimer's disease. Its clinical diagnostic utility for positron emission tomography or single photon emission computer tomography studies is being investigated.
Article
Glial cell monoamine oxidase (MAO) activity has been implicated as a contributor to oxidative neuronal damage associated with various neurodegenerative diseases. The attenuation of MAO activity may provide protection against oxidative neurodegeneration. In this investigation, the presence of MAO-B in rat C6 astrocyte cells was substantiated by dose-dependent inhibition of enzyme activity in the presence of chlorgyline-HCl and L-deprenyl. The present study evaluated various dietary-derived food constituents for evidence of inhibition on oxidative deamination of monoamines or peroxide radical trapping capacity. Results of this investigation indicate that compounds which inhibit C6 glial cell MAO enzyme activity or scavenge peroxide product include chlorogenic acid, (+)-catechin, taxifolin, (-)-epigallocatechin gallate (EGCG), fisetin, coenzyme Q0, curcumin, sesamol, morin, sesame oil, silymarin, green tea, ferulic acid, caffeic acid, and rutin hydrate. The results of this study indicate that dietary compounds can attenuate peroxide production in glial cells by either inhibiting the deamination of monoamines or acting as a free radical scavenger.
Article
Monoamine oxidase (MAO) catalyzes the oxidative deamination of a number of biogenic amines, including the key neurotransmitters serotonin (5-HT), norepinephrine (NE), and dopamine (DA) and the neuromodulator phenylethylamine (PEA). Two forms of MAO, designated “MAO A” and “MAO B,” have been identified on the basis of biochemical properties and, subsequently, by cloning the relevant genes. Of the two, MAO A exhibits a higher affinity for 5-HT and NE and for the inhibitor clorgyline (Johnston 1968), whereas MAO B has a higher affinity for PEA, benzylamine, and the inhibitor deprenyl (Knoll and Magyar 1972).
Article
Stimulus-response coupling systems responsible for defence and adaptation of organism to stressors are multi-target and very complicated pharmacological systems, including the neuroendocrine (stress) and immune system. The mode of action of adaptogens is basically associated with the stress-system (neuroendocrine-immune complex) and can be directed on the various targets of the system involved in regulation (activation and inhibition) of stimulus-response coupling. However, clinical studies performed according to the most modern standards are quite limited. On the other hand there is an extensive amount of clinical experience and also established use in self care etc. These aspects are planned to be dealt within a subsequent article which will be devoted to the application in three areas: self care, adjuvants in medicine and curative action in some diseases. At this stage, nevertheless, it seems possible to define some most important "stress-markers" for evaluation of efficiency of adaptogens in experimental and clinical pharmacological studies. They can be both activating (catecholamines, LT-s, cytokines, NO, etc.--"switch on" system--which activates energetic and other resources of the organism), and deactivating (corticosteroids and PGE2-endogenous mediators of cellular communications, which protect cells and whole organism from overreacting to the activating messengers--"switch off" system) stress-messengers. The balance between the activities of the "switch on" and "switch off" systems reflects the well being of the organism. It could be established on different levels of the homeostasis (heterostasis) with different levels of the sensitivity to stressors (Figure 8). The response of stress system--"reactivity" is different at the various levels of heterostasis and depends on adaptation--capacity of the organism (or a cell) to protect itself. In the process of adaptation to stressor's effects the basal levels mediators of switch on (e.g. NO) and switch of (e.g. cortisol) systems are increasing but their balance (the ratio) does not change. In other words, adaptogens increase the capacity of stress system to respond to external signals at the higher level of the equilibrium of activating and deactivating mediators of stress response. Consequently, plant adaptogens can be defined as "smooth" pro-stressors which reduce reactivity of host defense systems and decrease damaging effects of various stressors due to increased basal level of mediators involved in the stress-response. In further studies of adaptogens it seems important to find correlation between adaptogenic activity (a decrease in the "reactivity" of the organism--the basal level of activating and deactivating messengers: ILs, LTB4, NO, PGE2, cortisol, but not their ratio) and their therapeutic efficiency (symptomatic evaluation).
Article
Rhodiola rosea L. (Golden Root) has been used for a long time as an adaptogen in Chinese traditional medicine and is reported to have many pharmacological properties. Along its known secondary metabolites tyrosol (1), salidroside (rhodioloside) (2), rosin (3), rosarin (4), rosavin (5), sachaliside 1 (6) and 4-methoxy-cinnamyl-O-beta-D-glucopyranoside (7), four compounds were isolated from aqueous methanol extract of the plant and identified as cinnamyl-(6'-O-beta-xylopyranosyl)-O-beta-glucopyranoside (8), 4-methoxy-cinnamyl-(6'-O-alpha-arabinopyranosyl)-O-beta-glucopyranoside (9), picein (10) and benzyl-O-beta-glucopyranoside (11) by UV, MS and NMR methods. Compounds 8 and 9 are new natural compounds whereas compounds 10 and 11 were isolated first time from R. rosea. Also the compounds 6 and 7 are isolated earlier only from the callus cultures of the plant but not from the differentiated plant.
Article
A randomized, double-blind, placebo-controlled, parallel-group clinical study with an extra non-treatment group was performed to measure the effect of a single dose of standardized SHR-5 Rhodiola rosea extract on capacity for mental work against a background of fatigue and stress. An additional objective was to investigate a possible difference between two doses, one dose being chosen as the standard mean dose in accordance with well-established medicinal use as a psychostimulant/adaptogen, the other dose being 50% higher. Some physiological parameters, e.g. pulse rate, systolic and diastolic blood pressure, were also measured. The study was carried out on a highly uniform population comprising 161 cadets aged from 19 to 21 years. All groups were found to have very similar initial data, with no significant difference with regard to any parameter. The study showed a pronounced antifatigue effect reflected in an antifatigue index defined as a ratio called AFI. The verum groups had AFI mean values of 1.0385 and 1.0195, 2 and 3 capsules respectively, whilst the figure for the placebo group was 0.9046. This was statistically highly significant (p < 0.001) for both doses (verum groups), whilst no significant difference between the two dosage groups was observed. There was a possible trend in favour of the lower dose in the psychometric tests. No such trend was found in the physiological tests.
Article
The principal therapeutic agents used in the management of Parkinson's disease (PD) enhance nigrostriatal dopaminergic flux through either replenishment of depleted dopamine stores or the action of dopaminergic agonists. Adenosine A2A receptor antagonists (e.g., KW-6002) may provide symptomatic relief in PD and perhaps also may display neuroprotective properties based on studies in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of nigrostriatal neurodegeneration. A second class of compounds that is neuroprotective in the MPTP model comprises inhibitors of the outer mitochondrial flavoenzyme monoamine oxidase B (MAO B), one of the two forms of MAO that regulate levels of brain neurotransmitter substances, including dopamine. In this article, data are presented that document the overlapping A2A antagonist and MAO B inhibitory properties of several 2-styrylxanthinyl derivatives. A limited structure-activity analysis of these compounds and structurally related analogs is provided. The results raise the possibility that a single structure may offer the combined benefits of two pharmacologic strategies, each with symptomatic and potential neuroprotective benefits, for the management of PD.
Article
(-)-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase (MAO) B, which was discovered in 1962 and become the "golden standard" of MAO research. Like the other MAO-B inhibitors, it was synthesized as an antidepressant, but in a selective MAO-B inhibitory dose it does not act in depression. It is used in the treatment of Parkinson's disease. (-)-Deprenyl potentiates the effect of dopamine, it has antioxidant activity and prevents the toxicity of the dopaminergic (6-OH-dopamine; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)), the noradrenergic (DSP-4) and cholinergic (AF64A) neurotoxins after pre-treatment. When (-)-deprenyl was administered with levodopa in a long-term treatment of Parkinsonian patients, it induces adverse events (nausea, dizziness, confusion, hallucination, insomnia and cardiovascular changes), which could be due to dopamine potentiation in dopaminergic systems (limbic system), other than the nigrostriatal pathway. (-)-Deprenyl in much lower concentrations needed to induce MAO-B inhibition (10(-9) to 10(-13) M) potently inhibits MPTP or serum withdrawal induced apoptosis in tissue cultures of neuro-ectodermal origin (PC12, M1, M2058). The (+)-enantiomer of deprenyl lacks of this property. The anti-apoptotic activity of (-)-deprenyl can be prevented by inhibiting the metabolism of the drug with SKF-525A pre-treatment, which suggests that some of the presently unknown metabolites could be responsible for the anti-apoptotic activity. In high concentration (10(-3) M), (-)-deprenyl and its metabolites induce apoptosis in tissue cultures without serum withdrawal (biphasic action). Our findings support the view that 100, or even 1000 times lower dose of (-)-deprenyl can be offered in human therapy to protect, or slow down neuronal degeneration, than it is presently used. With low dose of the drug the dopaminergic adverse events could be avoided, while anti-apoptotic activity might be preserved.
Article
Interest in inhibitors of monoamine oxidase type B (MAO B) has grown in recent years, due to their therapeutic potential in aging-related neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. This study is devoted to the use of human recombinant MAO B obtained from a Baculovirus expression system (Supersomes MAO B, BD Gentest, MA, USA) as reliable and efficient enzyme source for MAO B inhibitor screening. Comparison of inhibition potencies (pIC50 values) determined with human cloned and human platelet MAO B for the two series of MAO B inhibitors, coumarin and 5H-indeno[1,2-c]pyridazin-5-one derivatives, showed that the difference between pIC50 values obtained with the two enzyme sources was not significant (P>0.05, Student's t-test). Hence, recombinant enzyme is validated as convenient enzyme source for MAO B inhibitor screening.
Article
Phenolic compounds from the aerial parts of medicinal plant Rhodiola rosea were identified using LC/MS experiments with time-of-flight and triple quadrupole instruments, providing accurate mass and CID fragmentation data about the compounds. Supercritical fluid extraction (SFE) was used to remove non-polar compounds from the samples, followed by liquid extraction of the flavonoids. Flavonoids were the main constituents in aerial parts of the plant, and no phenylpropanoids were detected. In addition to usual fragment ions providing the size of the attached glycosides in flavonoids, ions due to radical cleavage of glycosides were observed in the negative ion mode with relatively high collision energies. Use of these ions for elucidating the glycosylation site in the aglycone part was evaluated and was found to give some tentative information, but their use in unambiguous identification of unknown flavonoids is not recommended. Fifteen flavonoids, of which 10 were previously unreported from the plant, were identified.
Article
Five new monoterpene glycosides, rhodiolosides A-E (1-5), were isolated from the roots of Rhodiola rosea (Crassulaceae). Their structures were elucidated as (2E,6E,4R)-4,8-dihydroxy-3,7-dimethyl-2,6-octadienyl beta-D-glucopyranoside (1), (2E,4R)-4-hydroxy-3,7-dimethyl-2,6-octadienyl alpha-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (2), (2E,4R)-4-hydroxy-3,7-dimethyl-2,6-octadienyl beta-D-glucopyranosyl(1-->3)-beta-D-glucopyranoside (3), (2E,4R)-4,7-dihydroxy-3,7-dimethyl-2-octenyl beta-D-glucopyranoside (4), and (2E)-7-hydroxy-3,7-dimethyl-2-octenyl alpha-L-arabinopyranosyl(1-->6)-beta-D-glucopyranoside (5), on the basis of various spectroscopic analyses and chemical degradation.
Article
In comparison to the well-recognized adaptogenic herb Rhodiola rosea, phytochemical constituents of two other Rhodiola species (R. heterodonta and R. semenovii) were elucidated and characterized. Two major phytochemical groups; phenolic and/or cyanogenic glycosides and proanthocyanidins, were isolated and identified in the three species. Chemical similarities among the three species were observed; however, each species displayed differences in phytochemical constituents. R. heterodonta contained a newly detected phenylethanoid glycoside, heterodontoside, in addition to the known compounds tyrosol, viridoside, salidroside, and rhodiocyanoside A. Both R. heterodonta and R. rosea contained phenylethanoid/propanoid compounds that were not detected in R. semenovii. For R. semenovii, the cyanogenic glucosides rhodiocyanoside A and lotaustralin were detected. Although the three species have proanthocyanidins composed of (-)-epigallocatechin and its 3-O-gallate esters in common, the degree of polymerization greatly differed between them. In contrast to R. heterodonta and R. semenovii, R. rosea has higher molecular weight polymeric proanthocyanidins. This study resulted in the identification and isolation of phytochemical constituents for direct cross-comparison between three Rhodiola species of medicinal and pharmacological value.
Article
Rhodiola rosea L., or 'golden root', is a popular plant in traditional medicine in Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress. Due to these therapeutic properties, R. rosea is considered to be one of the most active adaptogenic drugs. To confirm and extend results obtained in the few preclinical and clinical studies available in English language journals, the purpose of the present study was to re-investigate the effects produced by a single oral administration of an R. rosea hydroalcohol extract (containing 3% rosavin and 1% salidroside) on the central nervous system in mice. The extract was tested on antidepressant, adaptogenic, anxiolytic, nociceptive and locomotor activities at doses of 10, 15 and 20 mg/kg, using predictive behavioural tests and animal models. The results show that this R. rosea extract significantly, but not dose-dependently, induced antidepressant-like, adaptogenic, anxiolytic-like and stimulating effects in mice. This study thus provides evidence of the efficacy of R. rosea extracts after a single administration, and confirms many preclinical and clinical studies indicating the adaptogenic and stimulating effects of such R. rosea extracts. Moreover, antidepressant-like and anxiolytic-like activities of R. rosea were shown in mice for the first time.
Article
Constituents in a distillation residue of Awamori (millet spirits) and their antioxidant activity are investigated in this study. The supernatant of the distillation residue obtained by centrifugation was partitioned with n-hexane, chloroform, ethyl acetate, and n-butanol against water to afford the corresponding solubles. Among them, n-hexane and chloroform solubles showed higher antioxidant potency than l-ascorbic acid by the bleomycin-Fe method. In chloroform solubles, seven cyclic dipeptides were identified along with ethyl 2-pyrrolidione-5-carboxylate, tyrosol, and ethyl p-hydoroxyphenyllactate. Antioxidant activity of ethyl p-hydoroxyphenyllactate was 4.2 times that of l-ascorbic acid, whereas cyclic dipeptides showed activity 0.89-1.29 times as strong as that of l-ascorbic acid. On the other hand, scavenging effect of cyclic dipeptides against O(2)(-.) and OH(.) by using electron spin resonance was also investigated. In the results, cyclo(l-Ile-l-Pro) showed significantly strong inhibitory effect against OH(.) (95.4% at 2.5 x 10-3 M) and cyclo(l-Phe-l-Pro), cyclo(l-Pro-l-Val), and cyclo(l-Leu-l-Pro) inhibited OH(.) 64.9, 54.1, and 51.0%, respectively, whereas alpha-tocopherol showed 37.7% inhibition, though only a few cyclic dipeptides weakly inhibited O(2)(-.).
Article
Column chromatography of hydrophilic extracts from Rhodiola rosea and Rodiola quadrifida led to the isolation of cinnamic alcohol, chlorogenic acid, rhodiooctanoside, rosiridin, rosavin and the phenolic compounds salidroside, rhodiolin and a novel compound consisting of viridoside with an attached arabinose unit (mongrhoside). HPLC analysis of plant material from different sources and from different collection periods showed a great variability in the composition and in the amount of pharmacologically active compounds contained.
Article
The antidepressant-like activity of an extract of the roots of Rhodiola rosea (RR), its combination with piperine containing extract (RPE), pure substances isolated from Rhodiola, such as rhodioloside, rosavin, rosin, rosarin, tyrosol, cinnamic alcohol, cinnamaldehyde and cinnamic acid has been assessed in laboratory animals through application of the Porsolt behavioural despair assay. RR increased the swimming time of rats in a dose dependent manner (ED50=7 mg/kg) and, when administered at 20mg/kg, exhibited a stronger anti-depressant type effect than either imipramine (at 30 mg/kg) or an extract of Hypericum perforatum (at 20mg/kg). Rhodioloside, and tyrosol were identified as active principles of the extract, whereas rosavin, rosarin, rosin, cinnamic alcohol, cinnamaldehyde, cinnamic acid were inactive. A fixed combination of rhodioloside, rosavin, rosarin and rosin was more active than any of the individual components alone, indicating a synergistic effect of the ingredients in RR extract. Piperine in combination with Rhodiola (RPE) distorts pharmacological effect of Rhodiola most probably due to changes of pharmacokinetic profile of rhodioloside and rosavin. RPE cannot provide predictable therapeutic effect due to herb-herb interaction. Moreover, concomitant treatment of RPE with other drugs should also be excluded due to drug-piperine interaction.
Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists Rhodiola rosea is a Valuable Medicinal Plant (Golden root) Monograph Tomsk State University Press
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Cinnamic glycosides of Rhodiola rosea rhizomes
  • Zapesochnaya
Zapesochnaya, G.G., Kurkin, V.A., 1982. Cinnamic glycosides of Rhodiola rosea rhi-zomes. Khimiya Prirodnykh Soedinenii, 723–727.
Phenylpropanoid glycosides from Rhodiola rosea
  • Tolonen