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Bioactive compounds from Rhodiola rosea (Crassulaceae)
Abstract
The methanol extract of the underground part of Rhodiola rosea was found to show inhibitory activity against Staphylococcus aureus. Bioactivity-guided fractionation of a 95% ethanol extract from the stems of R. rosea led to the isolation of five compounds: gossypetin-7-O-L-rhamnopyranoside (1), rhodioflavonoside (2), gallic acid (3), trans-p-hydroxycinnamic acid (4) and p-tyrosol (5). Their structures were elucidated by UV, IR, MS and NMR data, as well as by comparison with those of the literature. Compounds 1 and 2 were evaluated for their antibacterial and antiprostate cancer cell activities. Compounds 1 and 2 exhibited activity against Staphylococcus aureus with minimum inhibitory concentrations of 50 microg/mL and 100 microg/mL, respectively. Cytotoxicity studies of 1 and 2 also displayed activity against the prostate cancer cell line with IC(50) values of 50 microg/mL and 80 microg/mL, respectively.
... According to the Food and Agricultural Organization (FAO)/World Health Organization (WHO), acceptable cyanide level in edible plants is 10 mg HCN/kg dry weight. [32] Over the past few years, several methods of extraction for genus Rhodiola have been proposed to obtain the best extraction efficiency, considering most of all: water, [14,17,19,[33][34][35][36][37][38] ethanol, [10,18,19,25,34,37,[39][40][41][42][43][44][45][46][47][48] methanol [9,16,23,[49][50][51][52][53][54][55][56][57][58] and also acetone [59] and ethylacetate [19] as solvents. ...
... Numerous biological effects of Rhodiola species were tested both in vitro and in vivo in the studies conducted on bacteria, [55] mice, [18,19,23,33,34,36,37,48] rats [14,38,39,41,58] and humans. [7,15,17,20,21,33,46,[60][61][62] As the genus Rhodiola is of great interest among pharmacists, medics and researchers due to its composition and reported properties, there is a need to review and compare methods of its extraction and evaluation of included components. ...
... [63] Primarily roots of Rhodiola spp. are commonly used to extract contained compounds and there are mainly ethanolic, [10,18,37,[40][41][42]44,46,55] methanolic [16,23,[49][50][51]53,54,56,57] and aqueous [13,14,17,[33][34][35]37,38] extracts, rarely acetone [59] and ethylacetate [19] extracts. Among different extraction solvents, the use of acetone and methanol assured higher phenolic content from R. imbricata rhizomes and the extracts based on these two solvents gave comparable results in antioxidant activity. ...
This review presents an overview of the current knowledge regarding the techniques for the extraction of selected Rhodiola species, their bioactive compounds and their underlying mechanisms of action with particular emphasis on free radical scavenging properties. Rhodiola genus (Crassulaceae) is a perennial, which grows naturally in eastern Siberia, Scandinavia, Alaska and northern Europe that has been traditionally used in folk Asian medicine. In this review, we have done a critical evaluation of available literature on Rhodiola species roots and rhizomes, especially R. rosea (L.), R. imbricata (Edgew.), R. crenulata (Hook.f. & Thomson), R. kirilowii (Regel) and R. heterodonta (Hook.f. & Thomson), that have been most thoroughly investigated and described so far. Databases, including Scopus, PubMed and Google Scholar were applied to obtain relevant literature, based on reports mainly in the last 20 years. Here, we improved the list of the most important chemical compounds of Rhodiola spp. – mainly phenolic compounds and essential oils, taking into account their detection methods. In addition, we compared qualitatively and quantitatively different kind of extraction methods and analyzed the results regarding the antioxidant effects of Rhodiola species in vitro and in vivo on mouse and rat.
... The discovery of various functions of RRE subsequently drove the exploration of its active components. Since then, several secondary metabolites from RRE have been isolated, including phenylpropanoids, phenylethanol, flavonoids, monoterpenes and phenolic acids, with salidroside, tyrosol, rosavin, and triandrin as the main active components (Ming et al., 2005). Salidroside, which could be found in all Rhodiola species with concentrations ranging from 1.3 mg/g to 11.1 mg/g, has been known to possess various pharmacological properties ( Figure 1). ...
... The utilization of Rhodiola has emerged from its part or whole plants in the ancient era to RRE and, further, to the use of its active component, salidroside, in the modern era (Kelly, 2001;Ming et al., 2005;Panossian et al., 2010; Bayliak and Lushchak, (2017), Zhang et al. (2017) Frontiers in Pharmacology frontiersin.org 2011; Wang et al., 2013;Chen et al., 2017;Zheng et al., 2019;Zhuang et al., 2019). ...
Rhodiola is an ancient wild plant that grows in rock areas in high-altitude mountains with a widespread habitat in Asia, Europe, and America. From empirical belief to research studies, Rhodiola has undergone a long history of discovery, and has been used as traditional medicine in many countries and regions for treating high-altitude sickness, anoxia, resisting stress or fatigue, and for promoting longevity. Salidroside, a phenylpropanoid glycoside, is the main active component found in all species of Rhodiola. Salidroside could enhance cell survival and angiogenesis while suppressing oxidative stress and inflammation, and thereby has been considered a potential compound for treating ischemia and ischemic injury. In this article, we highlight the recent advances in salidroside in treating ischemic diseases, such as cerebral ischemia, ischemic heart disease, liver ischemia, ischemic acute kidney injury and lower limb ischemia. Furthermore, we also discuss the pharmacological functions and underlying molecular mechanisms. To our knowledge, this review is the first one that covers the protective effects of salidroside on different ischemia-related disease.
... Salidroside and tyrosol are active ingredients extracted from R. sachalinensis, a plant species mostly found in mountainous areas at high altitudes in northeastern Asia that has been used in traditional medicine for a long time [14]. Reports have shown that these compounds have a wide range of pharmacological properties, including anti-hypoxia, antioxidant, antifatigue, and anti-inflammation effects, as well as improvements in brain function [14,17]. ...
... Salidroside and tyrosol are active ingredients extracted from R. sachalinensis, a plant species mostly found in mountainous areas at high altitudes in northeastern Asia that has been used in traditional medicine for a long time [14]. Reports have shown that these compounds have a wide range of pharmacological properties, including anti-hypoxia, antioxidant, antifatigue, and anti-inflammation effects, as well as improvements in brain function [14,17]. Recently, salidroside and tyrosol were shown to significantly prevent ROS-induced brain ischemic injury in vivo and reduce oxidative stress by H 2 O 2 in vitro [18,40,41]. ...
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, which are accompanied by memory loss and cognitive disruption. Rhodiola sachalinensis (RSE) is a medicinal plant that has been used in northeastern Asia for various pharmacological activities. We attempted to carry out the bioconversion of RSE (Bio-RSE) using the mycelium of Bovista plumbe to obtain tyrosol-enriched Bio-RSE. The objective of this study was to investigate the effects of Bio-RSE on the activation of the cholinergic system and the inhibition of oxidative stress in mice with scopolamine (Sco)-induced memory impairment. Sco (1 mg/kg body weight, i.p.) impaired the mice’s performance on the Y-maze test, passive avoidance test, and water maze test. However, the number of abnormal behaviors was reduced in the groups supplemented with Bio-RSE. Bio-RSE treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. Bio-RSE dramatically improved the cholinergic system by decreasing acetylcholinesterase activity and regulated oxidative stress by increasing antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)). The reduction in nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in the brain tissue due to scopolamine was restored by the administration of Bio-RSE. Bio-RSE also significantly decreased amyloid-beta 1–42 (Aβ1–42) and amyloid precursor protein (APP) expression. Moreover, the increased malondialdehyde (MDA) level and low total antioxidant capacity in Sco-treated mouse brains were reversed by Bio-RSE, and an increase in Nrf2 and HO-1 was also observed. In conclusion, Bio-RSE protected against Sco-induced cognitive impairment by activating Nrf2/HO-1 signaling and may be developed as a potential beneficial material for AD.
... The MBC values of the preparations were, in most cases, greater than the MIC values. The antibacterial activity of R. rosea preparations has been the subject of very few studies [38][39][40]. Ming et al. [39] showed that the methanol extract of the underground part of R. rosea has inhibitory activity against Staphylococcus aureus. The effect of feeding mice with R. rosea extracts was studied on Pseudomonas aeruginosa infection by Bany et al. [41]. ...
... The antibacterial activity of R. rosea preparations has been the subject of very few studies [38][39][40]. Ming et al. [39] showed that the methanol extract of the underground part of R. rosea has inhibitory activity against Staphylococcus aureus. The effect of feeding mice with R. rosea extracts was studied on Pseudomonas aeruginosa infection by Bany et al. [41]. ...
Roseroot (Rhodiola rosea L.) belongs to plants revealing adaptogenic properties, which are attributed to the presence of specific phenolic compounds and are reflected mainly as antioxidant activity. The aim of the present study was to determine the antioxidant and antibacterial activity of various products obtained from R. rosea (underground organs as well as their aqueous and ethanolic dry extracts) in relation to the chemical profiles of phenolic and essential oil compounds. The chemical profiles were determined by High-performance Liquid Chromatography with a diode-array detector (HPLC-DAD) and Gas chromatography-mass spectrometry (GC-MS), antioxidant activity by (1,1-Diphenyl-2-picrylhydrazyl) Scavenging Capacity Assay (DPPH), (2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) Scavenging Capacity Assay (ABTS) and Ferric Reducing Antioxidant Power Assay (FRAP) and antimicrobial properties were expressed as minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) values following the broth microdilutions method. The results show that the investigated samples differed in terms of their chemical compositions and biological activities. The extracts were more abundant in phenolic compounds (salidroside, tyrosol, and rosavin derivatives) in comparison to dried underground organs. The content of the determined phenolics in the analyzed extracts was affected by the solvent used for extraction. The ethanolic extract was characterized by the highest content of these substances in comparison to the aqueous one and the dried raw material, especially with regard to rosavin (969.71 mg/100 g). In parallel, this extract showed the strongest antioxidant and antibacterial activity. However, dried R. rosea underground organs also revealed strong antibacterial effects against, for example, Staphylococcus strains.
... Salidroside (p-hydroxyphenethyl-D-glucoside) is extracted from Rhodiola plants, which have antiviral, neuroprotective, and hepatoprotective functions [5][6][7]. Salidroside can improve blood circulation and enhance immunity by lowering blood lipids [8,9]. Considerable evidence also suggests that salidroside has a protective effect on the heart. ...
Salidroside shows an inhibitory effect on myocardial ischemia/reperfusion (I/R) injury; however, the underlying mechanism remains to be explored. The present work analyzes the mechanism that drives salidroside to ameliorate I/R-induced human cardiomyocyte injury. Human cardiomyocytes were subjected to I/R treatment to simulate a myocardial infarction cell model. Cell viability, cell proliferation, and cell apoptosis were analyzed by CCK-8 assay, EdU assay, and flow cytometry analysis, respectively. RNA expression levels of circ_0097682, miR-671-5p, and F-box and ubiquitin-specific peptidase 46 (USP46) were detected by qRT-PCR. Protein expression was measured by Western blotting assay. The levels of IL-6, IL-1β, and TNF-α in cell supernatant were detected by enzyme-linked immunosorbent assays. Salidroside treatment relieved I/R-induced inhibitory effect on AC16 cell proliferation and promoting effects on cell apoptosis, inflammation, and oxidative stress. Salidroside inhibited circ_0097682 expression in I/R-treated AC16 cells. Salidroside-mediated inhibition of I/R-induced cell injury involved the downregulation of circ_0097682 expression. In addition, circ_0097682 bound to miR-671-5p in AC16 cells, and miR-671-5p inhibitors rescued salidroside pretreatment-mediated effects in I/R-treated AC16 cells. Moreover, miR-671-5p targeted USP46 in AC16 cells, and USP46 introduction partially relieved circ_0097682 depletion or salidroside pretreatment-induced effects in I/R-treated AC16 cells. Salidroside ameliorated I/R-induced AC16 cell injury by inhibiting the circ_0097682/miR-671-5p/USP46 pathway.
... Pharmacological studies on R. rosea are numerous [1,[8][9][10][11][12][13][14][15]. Adaptogenic properties of R. rosea are mostly related to the presence of these marker compounds [16], while antioxidant activity is mainly due to organic acids and flavonoids [17]. ...
Citation: Erst, A.A.; Kotsupiy, O.V.; Erst, A.S.; Kuznetsov, A.A. Individual Differences in Growth and in Accumulation of Secondary Metabolites in Rhodiola rosea Abstract: In this study, growth parameters of underground parts and concentrations of phenyl-propanoids, phenylethanoids, flavonoids, hydroxybenzoic acids, and catechins in aqueous-ethanol extracts of 6-year-old cultivated plants of Rhodiola rosea (propagated in vitro) of Altai Mountain origin were analyzed, and differences in chemical composition among plant specimens and between plant parts (rhizome and root) were evaluated. High-performance liquid chromatography detected 13 phe-nolic compounds. Roots contained 1.28 times higher phenylethanoids levels (1273.72 mg/100 g) than rhizomes did. Overall, the concentration of phenylethanoids in underground organs was not high and ranged from 21.36 to 103.00 mg/100 g. High variation among R. rosea individual plants was noted both in growth characteristics and in levels of secondary metabolites under our cultivation conditions. It was found that concentrations of phenylpropanoids, phenylethanoids, and catechins significantly depend on the plant part analyzed (p ≤ 0.05). Specimen No. 4 is characterized by the highest concentration of rosavins (1230.99 mg/plant) and the lowest concentration of cinnamyl alcohol (62.87 mg/plant). Despite the wide range of values, all 10 tested specimens (underground part) met the minimum requirements of the United States Pharmacopeia (2015) for rosavins (0.3%) and of the Russia State Pharmacopoeia (2015) for the average level of rosavins (roots): (1%).
... Phenolcarboxylic acids have been identified: gallic, rosmarinic, chlorogenic, caffeic, trans-p-hydroxycinnamic, methyl gallate, as well as flavonoids, including those in the aerial part of the plant [6,7,9,11,[21][22][23]. ...
The composition of the lipophilic components of the Rhodiola rosea L. plant was studied. Acidic and neutral components were identified by gas chromatography–mass spectrometry. With methyl-tert-butyl ether (MTBE) as an extractant instead of the volatile solvent diethyl ether, lipophilic extract was obtained.
Methyl-tert-butyl ether used as an extraction solvent for raw materials has all the advantages of diethyl ether, being free of its disadvantages. It does not form peroxides or produce elevated partial gas pressure due to its higher boiling point. As a result, comparison with databases identified some triterpene, phenolic, and aliphatic acids with chain lengths 12 to 30 carbon atoms, including saturated, unsaturated, and dibasic acids. In addition to the components known from the literature, more than 50 triterpene and aliphatic compounds were detected in the unsaponifiable residue and acidic fractions for the first time. The hexane extract and the product obtained by the stepwise extraction by MTBE after the extraction of low-polarity compounds with hexane were investigated in a similar way. In the case of an extract obtained using MTBE after the extraction
of low-polarity components with hexane, extraction of benzoic and cinnamic acids was more efficient compared to the exhaustive extraction of MTBE. These acids are absent from the hexane extract. Ethanol extraction was also carried out to test bioactivity: exhaustive and after hexane and MTBE extraction. Extracts obtained using MTBE and ethanol showed antiviral activity against the Ebola pseudovirus.
... Rhodiola rosea l, also known as 'golden root', is a perennial herbaceous plant of the crassulaceae family and is widely distributed in zones with severe cold, dry and hypoxic conditions at high altitude (3,500-5,000 meters) (8). in asia, Rhodiola rosea l is used as a herbal medicine to relieve certain symptoms, such as headache and hernias (9). in europe and north america, Rhodiola rosea l is used as a dietary supplement (10,11). according to modern pharmacology reports, the key metabolites of Rhodiola rosea l include phenethyl alcohol derivatives, monoterpenes, triterpenes, flavonoids and phenolic acids (12,13). Salidroside (Sal), a primary component, is extracted from the rhizome of Rhodiola rosea l. an increasing number of studies have reported that Sal not only demonstrates anti-hypoxia and anti-aging effects (14,15), but also demonstrates anti-fibrotic and immune regulatory effects (16,17). ...
Hepatocellular carcinoma (HCC) is the leading cause of cancer‑associated death in the world. Chemotherapy remains the primary treatment method for HCC. Despite advances in chemotherapy and modalities, recurrence and resistance limit therapeutic success. Salidroside (Sal), a bioactive component extracted from the rhizome of Rhodiola rosea L, exhibits a spectrum of biological activities including antitumor effects. In the present study, it was demonstrated that Sal could induce apoptosis and autophagy of 97H cells by using CCK‑8 assay, transmission electron microscopy (TEM), Hoechst33342 staining, MDC staining, western blotting. Pretreatment with Sal enhanced apoptosis and autophagy via upregulation of expression levels of Bax, Caspase‑3, Caspase‑9, light chain (LC)3‑II and Beclin‑1 proteins and downregulation of expression levels of Bcl‑2, LC3‑I and p62 protein in 97H cells. Furthermore, Sal was demonstrated to inhibit activation of the PI3K/Akt/mTOR signaling pathway and, when combined with autophagy inhibitor chloroquine diphosphate (CQ), increased phosphorylation of PI3K, Akt and mTOR proteins. The combined treatment with Sal and CQ not only decreased Sal‑induced autophagy, but also accelerated Sal‑induced apoptosis. Therefore, Sal‑induced autophagy might serve a role as a defense mechanism in human liver cancer cells and its inhibition may be a promising strategy for the adjuvant chemotherapy of liver cancer.
... Finally, the LAR subtype shows high expression of androgen receptor-related genes, including coactivators and hormone-regulated pathways. However, TNBC molecular subtypes were reclassified into four tumor-specific subtypes including BL1, BL2, M, and LAR after Lehmann et al. found that IM paired with MSL TNBC subtypes were presented by infiltrating lymphocytes and tumor-associated mesenchymal cells [59][60][61][62] . Inflammatory breast cancer: Isolated breast cancer is a rare kind of invasive breast cancer that has spread locally according to the TNM staging criteria. ...
Use of herbs and plants in cooking and medicinal dates back thousands of years. In this overview, we look at the many plant species that still have immune-boosting and cancer-fighting properties. Carotenoids, flavonoids, ligands, polyphenolics, terpenoids, sulphides, lignans, and plant sterols are only some of the many active phytochemicals found in different types of herbs. There are a number of mechanisms through which these phytochemicals exert their effects. They either prevent cell division or stimulate the synthesis of a protective enzyme such as glutathione transferase. The cancer-fighting and cholesterol-lowering effects of mevalonate are counteracted by the volatile oils and plant extracts from various herbs and plants.
... Rhodiola rosea L. (accepted name Sedum roseum (L.) Scop. according to www.theplantlist.org), also known as roseroot, artic-root, or golden root, is an adaptogen plant belonging to the Crassulaceae family [1][2][3][4][5]. R. rosea is distributed in China, Russia, Central, Northern Europe, and North America. ...
Roseroot, R. rosea, also commonly known as golden root or arctic root, is a perennial
herbaceous plant of the Crassulaceae family. R. rosea has its origin from the cold, humid
regions of the northern hemisphere and grows mostly in the mountains near the snow border.
R. rosea is widely distributed in Norway. As part of an effort to identify commercially valuable
genotypes characterization of a germplasm collection from Norway was initiated. Amplified
Fragment Length Polymorphism (AFLP) analysis was used to estimate genetic diversity within
the Norwegian R. rosea germplasm collection. AFLP analysis of 97 R. rosea clones using five
primer combinations gave a total of 95 polymorphic bands. A large molecular marker variation
was found among roseroot clones in Norway with an average percentage of polymorphic bands
(PPB) of 82.3%. Analysis of molecular variance (AMOVA) revealed a significantly greater
variation within regions (92.03%) than among regions (7.97%) demonstrating that there was no
close genetic similarity among clones originating from the same county. A low level of genetic
differentiation (FST = 0.043) was observed, indicating a high level of gene flow, which had a
strong influence on the genetic structure in Norway. Our results indicate high gene flow among
R. rosea clones that might be a result of seed dispersal rather than cross-pollination.
Ninety five clones were analysed and quantified for their content of the bioactive compounds
rosavin, salidroside, rosin, cinnamyl alcohol and tyrosol using High Performance Liquid
Chromatography (HPLC) analysis. All bioactive compounds were detected in all clones but in
highly variable quantities. The frequency distribution of the chemical content of each clone was
not correlated with geographic region of origin or gender of the plant. Significant correlations
between the content of these bioactive compounds were observed within individual roseroot
clones. Low and nonsignificant correlations were found between AFLP markers used to study
genetic diversity of the roseroot clones and their content of chemical compounds. The
maximum content of rosavin, rosin and salidroside observed were substantially higher than
previously reported for roseroot plants, and the roseroot clones characterized in this study might
therefore be of high pharmacological value.
The large quantitative and qualitative variation of the chemical compounds observed in this
study and the large genetic diversity observed in this germplasm constitute a firm basis for
improving traits such as chemical composition in a breeding program for roseroot.
This is the first report that combines the analysis of genetic diversity with information of the
chemical composition of roseroot.
... Rhodiola rosea root, an herbal medicine known as "golden root" or "arctic root", has been used as an antidepressant for years, and clinical trials have shown that it is effective (15). Previous findings have indicated that Rhodiola rosea contains hundreds of bioactive compounds, for example, phenylpropanoids, phenylethanol derivatives, flavanoids, monoterpernes, triterpenes, and phenolic acids (16), which are supposed to be involved in neuroprotective, cardio-protective, anti-fatigue, anti-stress, anti-depressive, and anxiolytic activities, and immunity improvement (17). Nonetheless, the molecular mechanism of Rhodiola rosea in the treatment of depression is still unknown. ...
Background:
Depression is one of the most common psychiatric disorders worldwide. Many antidepressant drugs are only effective for specific patients and their long-term use can lead to treatment resistance. There is an ongoing need for more effective antidepressant treatments.
Methods:
The rats were exposed to chronic unpredictable mild stress (CUMS) to induce depression model. The glutamate level in the hippocampus was determined by high performance liquid chromatography (HPLC). Protein levels in the tissues were measured using western blotting. The fluid consumption test was performed to evaluate potential anhedonia. Open field test was conducted to evaluate locomotor activity. Forced swimming test was used to evaluate susceptibility to negative mood.
Results:
In the present study, the depressive-like behaviors induced by CUMS were alleviated in rats by treatments with Herba Rhodiolae (0.04 g/kg, 1 mL), venlafaxine (0.035 g/kg, 1 mL), and combination of Herba Rhodiolae and glycogen synthase kinase 3 beta (GSK-3β) inhibitor (10 µM, 1 mL). Among these treatments, the combination of Herba Rhodiolae and GSK-3β inhibitor was most effective. Abnormalities in the glutamate system and autophagy of the brain were decreased greatly in Herba Rhodiolae and GSK-3β inhibitor-treated CUMS rats. Herba Rhodiolae was more effective in promoting the brain derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The expression of GSK-3β was remarkably suppressed by the GSK-3β inhibitor.
Conclusions:
These findings indicated that the combined effects of Herba Rhodiolae and GSK-3β inhibitor contributed to the activation of BDNF/TrkB-GSK-3β signaling pathway.
... Finally, it has been shown in human colon cancer cells that low concentrations of BJ can induce inhibition of the mitogen-activated protein kinase (MAPK)-dependent pathways, and cause cell cycle arrest and alteration of apoptosis, while high concentrations produce oxidative stress, causing DNA damage [121]. BPF has attracted scientific attention for its peculiar composition and high content of flavonoids, such as naringin, hesperidin, and neoeriocitrin [79]. Although few studies on the correlation between BPF and cancer are available, multiple papers indirectly involving BPF are known. ...
Cancer is one of the leading causes of death globally, associated with multifactorial pathophysiological components. In particular, genetic mutations, infection or inflammation, unhealthy eating habits, exposition to radiation, work stress, and/or intake of toxins have been found to contribute to the development and progression of cancer disease states. Early detection of cancer and proper treatment have been found to enhance the chances of survival and healing, but the side effects of anticancer drugs still produce detrimental responses that counteract the benefits of treatment in terms of hospitalization and survival. Recently, several natural bioactive compounds were found to possess anticancer properties, capable of killing transformed or cancerous cells without being toxic to their normal counterparts. This effect occurs when natural products are associated with conventional treatments, thereby suggesting that nutraceutical supplementation may contribute to successful anticancer therapy. This review aims to discuss the current literature on four natural bioactive extracts mostly characterized by a specific polyphenolic profile. In particular, several activities have been reported to contribute to nutraceutical support in anticancer treatment: (1) inhibition of cell proliferation, (2) antioxidant activity, and (3) anti-inflammatory activity. On the other hand, owing to their attenuation of the toxic effect of current anticancer therapies, natural antioxidants may contribute to improving the compliance of patients undergoing anticancer treatment. Thus, nutraceutical supplementation, along with current anticancer drug treatment, may be considered for better responses and compliance in patients with cancer. It should be noted, however, that when data from studies with bioactive plant preparations are discussed, it is appropriate to ensure that experiments have been conducted in accordance with accepted pharmacological research practices so as not to disclose information that is only partially correct.
... In recent years, in vivo and in vitro experiments have proved that the compound has positive effects on anti-cancer, anti-in ammatory, anti-oxidation, neuroprotection, myocardial protection, liver protection, kidney protection. It has extremely important application value in military, aerospace, sports and health medicine [53][54][55][56]. In addition, it is reported that salidroside can inhibit the release of LDH, CK and AST of human cardiomyocytes by increasing the expression of HIF-1α, increase the content of SOD, and at the same time increase the activity of human cardiomyocytes and reduce the death and apoptosis of cells [57]. ...
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.
... This indicates the presence of more than one active principle of Ipomoea aquatica FORSK. Plants are richest reservoir of antimicrobials [80] it is observed that a plant is known to contain several active principles of biological significance [81]. The present finding is hence highly encouraging in recognizing a plant of interesting antibacterial activity. ...
Infectious diseases are the leading cause of death worldwide. Antibiotic resistance has become a global concern. The present study also gives for the first time the phytochemical profile of all the extracts used in the present study. Since alkaloids are the secondary metabolites, whose function is known to be defensive to the plant. Further work needs to be carried out to confirm where the alkaloids are responsible for the desired activity. This also serves as important information for further isolation and purification of the active principles from this plant. In the present study, the plant extracts is significantly against the pathogens. Though it is also expressed the phytochemical compounds presence in the plant, it was interesting to observe that there was a reduced to absent in some extracts. It is the view that these different extracts showed which could be precursor to infectious diseases. Since compounds of biological origin are known to posses minimal residual effect. The most active extracts can be subjected to isolation of the therapeutic and carry out further pharmacological evaluation.
... Rhodiola and Kalanchoe genera are employed in traditional medicine as antimicrobial, anti-inflammatory and antitumor agents (Brown et al., 2002;Yadav and Dixit, 2003). The isolation and identification of bioactive compounds belonging to phenolics, sterols and terpenes was also reported (Ming et al., 2005;Quazi Majaz et al., 2011;Tayade et al., 2013). They were previously reviewed for their traditional uses, chemical content and biological activities (Milad et al., 2014;Tao et al., 2019). ...
Family Crassulaceae is a large family of dicotyledonous angiosperms characterized by its unique form of photosynthesis. Although plants of this family are used mainly as ornamental plants, many reports are found discussing the chemical content and biological efficacy of many members of this family. Phenolic compounds are among the most prevalent chemical moieties. On the other hand, many biological activities such as anti-inflammatory, antimicrobial, antioxidant, anticonvulsant, anticancer and antidiabetic are recorded for several species. The present study reviews the phytochemical content and the biological activities of forty species belonging to nine genera of the family Crassulaceae; Aeonium, Crassula, Echeveria, Hylotelephium, Jovibarba, Orostachys, Sedum, Sempervivum and Sinocrassula during the last ten years. The isolation of 189 compounds of phenolics, flavonoids, sterols, triterpenes, nitrogen-containing compounds and other miscellaneous compounds is reported. Moreover, the biological activities of these genera are reviewed. This study indicates that several species have not been adequately studied in terms of their chemical content or biological effect. Hence, it provides a source for selecting species for phytochemical or biological exploration. The provided information may inspire new biomedical application for different species of the selected genera.
... 14.3.4.6 Toxicity of Rhodiola rosea According to present scientific reports, there is no adverse effect of R. rosea (Ming et al. 2005). But if taken in large amount, it is lethal. ...
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.
... 14.3.4.6 Toxicity of Rhodiola rosea According to present scientific reports, there is no adverse effect of R. rosea (Ming et al. 2005). But if taken in large amount, it is lethal. ...
... According to present scientific reports, there is no adverse effect of R. rosea (Ming et al. 2005). But if taken in large amount, it is lethal. ...
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.
... The dichloromethane-methanol (1:1) extract of T. vogelii seedpods was subjected to silica gel and Sephadex LH-20 column chromatography followed by preparative reverse phase HPLC to give two new isoflavones (1 and 2) (Fig. 1) along with ten known compounds. By comparison of the NMR data with literature, the known compounds were identified as isopongaflavone (3) [27], onogenin [28], luteolin [29], 4′,7-dihydroxy-3′-methoxyflavanone [30], trans-p-hydroxycinnamic acid [31], tephrosin [32], 2-methoxygliricidol [33], dehydrorotenone [34], 6a,12a-dehydro-α-toxicarol [35,36] and pinoresinol [37]. ...
Phytochemical investigation of Tephrosia vogelii seedpods led to the isolation of twelve compounds: vogelisoflavone A (1), vogelisoflavone B (2), isopongaflavone (3), onogenin, luteolin, 4′,7-dihydroxy-3′-methoxyflavanone, trans-p-hydroxycinnamic acid, tephrosin, 2-methoxygliricidol, dehydrorotenone, 6a,12a-dehydro-α-toxicarol and pinoresinol. Compounds 1 and 2 are reported as new natural products. Isopongaflavone (3) was structurally modified using hydrazine to pyrazoisopongaflavone (4). These compounds were characterized based on their NMR and HRESIMS data. Further, four compounds (1–4) were evaluated for their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the compounds at a concentration of 100 μM suppressed the secretion of interleukin IL-1β interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α).
... Rhodiola rosea L. (accepted name Sedum roseum (L.) Scop. according to www.theplantlist.org), also known as roseroot, artic-root, or golden root, is an adaptogen plant belonging to the Crassulaceae family [1][2][3][4][5]. R. rosea is distributed in China, Russia, Central, Northern Europe, and North America. ...
Rhodiola rosea L. (roseroot) is an adaptogen plant belonging to the Crassulaceae family. The broad spectrum of biological activity of R. rosea is attributed to its major phenyletanes and phenylpropanoids: rosavin, salidroside, rosin, cinnamyl alcohol, and tyrosol. In this study, we compared the content of phenyletanes and phenylpropanoids in rhizomes of R. rosea from the Norwegian germplasm collection collected in 2004 and in 2017. In general, the content of these bioactive compounds in 2017 was significantly higher than that observed in 2004. The freeze-drying method increased the concentration of all phenyletanes and phenylpropanoids in rhizomes compared with conventional drying at 70 • C. As far as we know, the content of salidroside (51.0 mg g −1) observed in this study is the highest ever detected in Rhodiola spp. Long-term vegetative propagation and high genetic diversity of R. rosea together with the freeze-drying method may have led to the high content of the bioactive compounds observed in the current study.
... It is also called Solomon's lily, priest's hood, kardi and black calla. It is grown in march and april month by which the plant is easily recognized by its dark purplish black spadix enclosed by a reddish brown spathe (Avi Shmida;2005). It is light green, narrow and upright with a purplish black color. ...
Arum palestinum is an important medicinal plant belonging to the family Araceae. It is basically found in North America, North Africa, Europe and Australia. It is an Ancient medicine that is generally used in Cancer. The aim of this review gives the information about the bioactive compounds and phytochemicals such as phenolics, carotenoides and flavonoids are naturally found in Arum palestinum Boiss which act as defense mechanism against various types of cancer cell lines and also act as antioxidant and anti inflammatory in human being such as Lung cancer, Breast cancer, Liver cancer, Prostate, Colorectal cancer as well as Stomach cancer. Such types of investigations are characterized of these bioactive compounds potential is vital.
... The susceptibility of the UTI pathogens varied for polar solvent extracts and non-polar solvent extracts. This indicates the contribution of more than one active principle of biological significance for botanicals (Ming et al. 2005). The traditional healers use mainly water as the solvent, but we observed that extracts prepared from the E. tectorius leaf in ethyl acetate, methanol, and water as solvents provided a more reliable anti-microbial activity against target pathogens (Parekh 2007). ...
... Rhodiola crenulata (perennial of the Crassulaceae family), native to the Qinghai-Tibet Plateau, is one of the most important medicinal plant products used by Tibetans in Chinese Traditional Medicine [1]. Salidroside, one of the major phenolic glycoside extracted from Rhodiola rosea, is often used as the criterion for qualitative evaluation of crude drugs. ...
Salidroside is one of the bio-active compounds found in Rhodiola crenulata. To find an easy, time saving and efficient way to extract, purify and enrich salidroside from Rhodiola and other natural plants, we prepared a highly selective molecularly imprinted polymer (MIP) for extraction and preconcentration of salidroside using salidroside (SD) as a template, acrylamide (AM) as a functional monomer, ethylene glycol dimethacrylate (EDMA) as a crosslinking monomer, and dimethyl formamide (DMF) as a porogen. The performance of the MIPs was evaluated through selective recognition capacity and adsorption isotherms and kinetics. The results showed that MIPs possessed excellent specific recognition toward SD and could effectively discriminate its structural analogue. The application of the developed MIPs as a selective sorbent for solid-phase extraction (SPE) of SD was also investigated. Under the optimum conditions, a rapid, economical, and efficient method based upon MIP-SPE coupled with high-performance liquid chromatography (HPLC) was developed for the determination of SD in Rhodiola crenulata. The method showed satisfactory recoveries (from spiked real samples at 3 fortification levels of 0.5, 1 and 10 mg L −1) of 88.74%-97.64% with relative standard deviations (RSDs) ranging from 2.05%-3.54%. Furthermore, MIP-SPE was successfully used to separate and purify SD from different parts in Rhodiola crenulata and it should be available for determination of salidroside in others herbs.
... 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. ...
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.
... However, even if a material is found to improve prostate enlargement from natural products, it takes a long time to clarify the mechanism [11,12]. Therefore, considering that prostate hyperplasia is a long-standing disease according to aging, it is best to find a material that can prevent and treat enlargement of the prostate by effectively taking it safely for a long period. ...
The effect of Rhodiola sachalinensis Boriss extract irradiated with 50 kGy gamma rays (HKC) on benign prostatic hyperplasia (BPH) was investigated. Seven-week-old male SD rats received a subcutaneous injection of 20 mg/kg of testosterone propionate (TP) to induce BPH. Then, the testosterone only group received testosterone, the testosterone + finasteride group received testosterone and finasteride (5 mg/kg), the testosterone + HKC group received testosterone and HKC extract (500 mg/kg). Prostate weight and the dihydrotestosterone (DHT) levels in serum or prostate tissue were determined. The mRNA expressions of 5-alpha reductase (AR) in prostate tissue were also measured. Compared to the control group, prostate weight was significantly improved in the TP group and decreased in the HKC and finasteride-treated groups. Furthermore, the mRNA expression of 5-AR in the prostate was significantly reduced in the HKC and finasteride-treated groups. Similarly, the expression levels of α-smooth muscle actin (α-SMA) and cytokeratin, which are associated with prostatic enlargement in the HKC and finasteride groups, were much lower than in the TP group. HKC treatment showed similar efficacy to finasteride treatment on rats with testosterone-induced BPH. HKC may be explored as a potential new drug for BPH treatment.
... a, R. crenulata; b, R. rosea; c, R. sachalinensis; d, R. kirilowii; e, R. sacra; f, R. quadrifida; g, R. dumulosa identified across Rhodiola species, such as R. crenulata, R. rosea, R. sachalinensis, R. sacra, R. kirilowii, R. quadrifida, and R. quadrifida. 50,55,80,83,91,94,97,105 Nine gallic acid derivatives isolated from R. crenulata are as follows: 3-O- methylgallic acid (Compound 78), 80 methyl gallate (Compound 79), 46,92,106 gallic acid ethyl ester (Compound 80), 94,99 4-O-β-D-glucopyranosyloxy-3,5-dimethoxybenzoic acid (Compound 82), 80 as Compound 92 is a nitrile compound, its potential toxicity should be taken into consideration. Though gallic acid derivatives are widely distributed in the Plant Kingdom, they might be important material basis of Rhodiola plants due to their bioactivities. ...
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.
... At a concentration of 100 µg/ml, extracts in the different solvents conferred 7.6%, 29.3%, and 24.3% neuroprotection, respectively. These findings suggest that the Rhodiola rosea extract has potential therapeutic effects for AD, especially the EtOAc-based extract [14]. ...
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.
... Symptoms that seem particularly good targets for rhodiola include fatigue, stress, depression, and sexual dysfunction (Iovieno et al. 2011). Rhodiola's "adaptogenic" chemicals include rosavins, salidroside, and p-tyrosol (Ming et al. 2005), as well as antioxidant flavonoids and organic acids. Rhodiola also may modulate monoamines and catecholamines by inhibiting the enzymes MAO-A and MAO-B (Kelly 2001;van Diermen et al. 2009). ...
Depression remains difficult to manage, despite the many registered treatments available. For many depressed individuals, particularly those who have not responded to and/or had adverse effects from standard therapies, herbal and natural medications represent a potentially valuable alternative. This chapter will review several natural remedies used in the treatment of depression. Specific remedies covered include St. John’s wort (SJW), S-adenosyl-L-methionine (SAMe), omega-3 fatty acids, rhodiola, and others. We will begin by providing some historical and social context about these remedies. Then we will review efficacy and safety data, as well as biological mechanisms of action of these therapies. Finally, we will discuss the limitations of the current state of knowledge and provide suggestions for a productive research agenda focused on natural remedies. While many questions about these treatments remain unanswered and much work needs to be done before we determine their place in the psychiatric armamentarium, we believe that this chapter will give psychiatrists a good perspective on the pros and cons of herbal and natural antidepressants as part of the pharmacological armamentarium and sensible guidelines on how and when they should be used.
... Salidroside is a primary component of Rhodiola rosea L., which is used in traditional Chinese medicine (14). Several clinical and experimental studies have identified that salidroside exhibits multiple pharmacological activities, including anti-oxidation, anti-apoptosis, anti-inflammation, anti-stress and enhancement of immune function (15)(16)(17). It has also been demonstrated that salidroside has a protective effect on myocardial I/R injury, which is associated with anti-oxidative stress and anti-apoptosis (18,19); however, its exact underlying mechanisms have not yet been determined. ...
Endoplasmic reticulum (ER) stress‑induced apoptosis serves a crucial role in the development of myocardial ischemia/reperfusion (I/R) injury. Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., which is a plant often used in traditional Chinese medicine. It possesses multiple pharmacological actions and protects against myocardial I/R injury in vitro and in vivo. However, it is not yet clear whether ER stress or ER stress‑induced apoptosis contributes to the cardioprotective effects of salidroside against myocardial I/R injury. Hence, hypoxia/reoxygenation (H/R)‑treated H9c2 cardiomyocytes were used in the current study to mimic myocardium I/R injury in vivo. It was hypothesized that salidroside alleviates ER stress and ER stress‑induced apoptosis, thereby reducing H/R injury in H9c2 cells. The results demonstrated that salidroside attenuated H/R‑induced H9c2 cardiomyocyte injury, as cell viability was increased, lactate dehydrogenase release was decreased, morphological changes in apoptotic cells were ameliorated and the apoptosis ratio was reduced compared with the H/R group. ER stress was reversed, indicated by the downregulation of glucose regulated protein 78 and C/EBP homologous protein following pretreatment with salidroside. In addition, salidroside attenuated ER stress‑induced apoptosis, as the expression of cleaved caspase‑12 and pro‑apoptotic protein Bcl‑2 associated X protein and activity of caspase‑3 was decreased, while the expression of anti‑apoptotic protein Bcl‑2 was increased following pretreatment with salidroside. Furthermore, the results indicated that salidroside decreases the activation of the ER stress‑associated signaling pathway, as the expression of phosphorylated protein kinase RNA (PKR)‑like ER kinase (p‑PERK) and phosphorylated inositol‑requiring enzyme‑1α (p‑IRE1α) proteins were decreased following pretreatment with salidroside. These results demonstrate that salidroside protects against H/R injury via regulation of the PERK and IRE1α pathways, resulting in alleviation of ER stress or ER stress‑induced apoptosis in H9c2 cardiomyocytes.
... kaempferol, isorhamnetin, and myricetin, as well as flavonoid glycosides(AlberTi-dér, 2013;erTAs et al., 2014;miNg et al., 2005;siNgAb et al., 2011;TATsimO et al., 2012), which are commonly 3,7-O-disubstituted glycosides of rhamnose and glucose(AlberTi-dér, 2013;milAd et al., 2014;siNgAb et al., 2011). Every studied Echeveria species showed a specific profile of phenolics; most Crassulaceae plants contain derivatives of the flavonoid aglycones quercetin, isorhamnetin, and kaempferol. ...
Echeveria species (Crassulaceae) are used in traditional medicine and some of their biological activities are demonstrated (e.g. antimicrobial, anti-inflammatory, anticancer). However, their chemical composition has been scarcely studied. The methanol extracts (ME) of three Echeveria species (E. craigiana, E. kimnachii and E. subrigida) from Mexico were analyzed for the sterol (GC-MS) and phenolic (HPLC-DAD-ESI-MSn) composition. Eleven sterols were identified, E. kimnachii showed the highest total content (7.87 mg/g ME), and the main constituents were γ-sitosterol in E. craigiana (33.9%) and E. subrigida (54.4%), and lupenone in E. kimnachii (28.9%). The phenolic analysis showed differences among the Echeveria species, which contained flavonoids derivatives and tannins as the main components. The main flavonoids in E. craigiana were hexoside derivatives of quercetin and isorhamnetin, both with a 3-hydroxy-3-methylglutaroyl substituent; in E. subrigida hexosides of isorhamnetin, quercetin and kaempferol; and E. kimnachii showed the greatest diversity including proanthocyanidins and less common flavonoid derivatives of kaempferol O,O-disubstituted by acyl derivatives. The characteristic phytochemicals of each studied Echeveria species could be responsible of its specific biological activities and useful as chemotaxonomic markers. The kaempferol derivatives in E. kimnachii are rare in nature and they will be isolated and characterized.
... This assay is routinely utilized to study mechanistic signaling pathways associated with BCSC and possible therapeutic intervention routes. Rhodiola is a perennial plant that grows in barren soil in the high tundra regions of Siberia and the highlands of Tibet and has been used in traditional eastern medicine (55). There are ~90 different Rhodiola plant species, all exhibiting a variety of health-promoting effects. ...
Females with early-stage metastatic, estrogen-dependent breast cancer are generally treated with surgery, radiation and chemotherapy, or with more targeted approaches such as aromatase inhibitors (anastrozole or letrozole) or anti-estrogens (tamoxifen). Despite widespread successful usage of these agents for the treatment of breast cancer, resistance, tumor relapse and metastasis remain the principal causes of mortality for patients with breast cancer. While numerous groups have made major contributions toward an improved understanding of resistance mechanisms, the currently insufficient grasp of the most critical pathways involved in resistance is evident in the inability to adequately treat and drastically improve patient outcomes in females with hormone-refractory breast cancer, including triple negative breast cancer. Therefore, further investigation of novel therapeutic approaches is paramount to reveal previously unconsidered agents that could be utilized to treat metastatic disease. Numerous naturally occurring phytochemicals have recently gained interest as potential therapeutic breast cancer agents appear to directly affect estrogen-dependent and estrogen-independent breast cancer cell proliferation, potentially via affecting breast cancer stem cell populations. While numerous natural compounds have exhibited promise, they are limited by their bioavailability. Therefore, to effectively treat future hormone-refractory breast tumors, it is critical to adequately refine and formulate these agents for effective therapeutic use and delivery. Herein, the literature on the current state of phytochemicals is reviewed, including their limitations and potential as targeted therapies for breast cancer.
Planar chromatography has recently been combined with six different effect-directed assays for three golden root (Rhodiola rosea L.) samples. However, the profiles obtained showed an intense tailing, making zone differentiation impossible. The profiling was therefore improved to allow for the detection of individual bioactive compounds, and the range of samples was extended to 15 commercial golden root products. Further effect-directed assays were studied providing information on 15 different effect mechanisms, i.e., (1) tyrosinase, (2) acetylcholinesterase, (3) butyrylcholinesterase, (4) β-glucuronidase, and (5) α-amylase inhibition, as well as endocrine activity via the triplex planar yeast antagonist-verified (6–8) estrogen or (9–11) androgen screen, (12) genotoxicity via the planar SOS-Umu-C bioassay, antimicrobial activity against (13) Gram-negative Aliivibrio fischeri and (14) Gram-positive Bacillus subtilis bacteria, and (15) antioxidative activity (DPPH• radical scavengers). Most of the golden root profiles obtained were characteristic, but some samples differed substantially. The United States Pharmacopeia reference product showed medium activity in most of the assays. The six most active compound zones were further characterized using high-resolution mass spectrometry, and the mass signals obtained were tentatively assigned to molecular formulae. In addition to confirming the known activities, this study is the first to report that golden root constituents inhibit butyrylcholinesterase (rosin was tentatively assigned), β-glucuronidase (rosavin, rosarin, rosiridin, viridoside, and salidroside were tentatively assigned), and α-amylase (stearic acid and palmitic acid were tentatively assigned) and that they are genotoxic (hydroquinone was tentatively assigned) and are both agonistic and antagonistic endocrine active
Rhodiola rosea roots and rhizomes hold an important place in the folk medicines of Russia, Scandinavia, Mongolia, and China as a health supplement for stimulating the nervous system, enhancing physical and mental performances, and nowadays they constitute the active ingredient in many popular commercial preparations sold worldwide as food additives, pharmaceutical remedies, and drinks. This study was aimed at providing a detailed phytochemical characterization of the Rhodiola 5%, a commercially available extract of R. rosea roots, and resulted in the characterization of 18 secondary metabolites, including 13 polyphenols and 6 terpenoids, and in the discovery of the new rhodiosidin (5), the first R. rosea metabolite to show both terpenoid and cinnamoyl moieties. The 5-lipoxygenase inhibiting activity of the main components was characterized and disclosed that rosiridin (6), kenposide A and rosavins are mainly responsible for this activity of the extract.
Oleoresin is a mixture of volatile and nonvolatile components available in whole extract of natural herb or spice. It principally comprises essential oils and resin. Lemongrass oleoresins come from the Cymbopogon species, which grow in the tropical and subtropical regions of the world. Oleoresin of lemongrass is a dark green-colored viscous liquid having a characteristic lemon aroma and flavor and is mostly used as a flavoring ingredient. The lemon prefix in the lemongrass specifies the characteristic lemon-like odor, which is due to the availability of citral content (mixture of two isomeric aldehydes, geranial and neral). It has been utilized in synthesizing flavors, perfumes, cosmetics, detergents, and in the food and pharmaceutical industries. Different methods are used to extract the lemongrass essential oil, but steam distillation is the most suitable method as it doesn’t alter the quality of the obtained oil. The chemical composition of lemongrass oil varies depending on its extraction methods, genetic differences, harvest period, photoperiod, plant age, farming practices, and geographical origin. Lemongrass essential oil has shown several biological activities, including antimicrobial, antifungal, antiprotozoan, antioxidant, antidiarrheal, antimutagenic, antiinflammatory, antimalarial, antinociceptive, antihepatotoxic activities, etc. Lemongrass oil is a potent food preservative because of its extraordinary antifungal and antibacterial activities.
The composition of the plant Rhodiola rosea L. lipophylic substances was studied. Acidic and neutral components were identified by gas-chromatography-mass-spectrometry. With methyl-tert-butyl ether (MTBE) as an extractant instead of the volatile solvent diethyl ether, lipophylic extract was obtained. Methyl-tert-butyl ether used as an extraction solvent for raw materials has all the advantages of diethyl ether, being free of its disadvantages. It does not form peroxides or produce elevated partial gas pressure due to its higher boiling point. As a result, comparison with databases identified some triterpene, phenolic and aliphatic acids with chain lengths 12 to 30 carbon atoms, including saturated, unsaturated, and dibasic acids. In addition to the components known from the literature, more than 50 triterpene and aliphatic compounds were detected in the unsaponifiable residue and acidic fractions for the first time. The hexane extract and the product obtained by the stepwise extraction of MTBE after the extraction of low-polarity compounds with hexane were investigated in a similar way. In the case of an extract obtained using MTBE after the extraction of low-polarity components with hexane, there was shown a more efficient extraction of benzoic and cinnamic acids compared to the exhaustive extraction of MTBE. These acids are absent in the hexane extract. Ethanol extraction was also carried out to test bioactivity: exhaustive and after hexane and MTBE extraction. Extracts obtained using MTBE and ethanol showed anti-virus activity against Ebola psevdovirus.
Adulterations of food and pharmaceutical preparations are the important global problem. On the one hand, fraud practices are becoming more and more sophisticated while on the other, monitoring and uncovering falsifications are insufficient. One of the most common consumer concern is the quality and authenticity of the purchased products, related to the confidence that they have composition and properties in accordance with the manufacturer's declaration on the label. This refers also to pharmaceuticals potentially delivering great health benefits such as Rhodiola rosea L. supplements. The aim of this study was defining authenticity and possible adulterations of two R. rosea preparations basing on their TLC-bioprofiles and the presence of biomarker compounds characteristic for this plant. The effect-directed analysis (EDA), i.e. TLC hyphenated with micro-chemical and biological assays performed directly on TLC plates followed by HPLC-ESI-MS was used for the bioprofiling of antioxidants, antibacterials, and inhibitors of lipase, acetylcholine, α-glucosidase and tyrosinase as well as for the identification of the biomarkers. The results pointed to the possible adulteration of one of the tested products related to the absence of two rosavins, the most important quality markers of R. rosea.
Herbacetin (HBN) is an antiviral agent of H1N1 influenza virus which was reported to inhibit H1N1 neuraminidase (NA) enzyme with IC50 value of 8.9 μM. The research exploration for HBN was conducted via quantum chemical calculations and spectroscopic techniques. The experimental vibrational FT-IR and FT-Raman spectra of the HBN molecule were obtained, and it was compared with theoretical method utilizing quantum chemical calculations through DFT approach employing basis sets 6-31G(d,p) and 6-311G(d,p). The MEP, NBO, global and local reactivity descriptors were carried out to describe the reactivity, selectivity and stabilization of the HBN molecule. The electronic characteristics namely UV-Vis and HOMO-LUMO were computed through TD-DFT method which was correlated with experimental spectral analysis. The total, partial and overlap population density of states (DOS) were carried out to confirm the molecular orbital contributions. The drug likeness and ADMET predictions were analysed to reveal the biological behaviour of the HBN. Furthermore, the molecular docking investigation is to find the best fit orientation: binding mode, inhibition constant and intermolecular interactions among HBN and NA enzyme. The ligand molecule fits very well in the NA active site cavity. Hence, the HBN molecule exhibits good biological activity, and it can be served as a prospective drug for H1N1 influenza A virus.
Graphical abstract
Background
Lung cancer is the most common and mortal cancer worldwide. Rhodiola rosea L. (RR), a well-known traditional Chinese medicine (TCM), has been turned out to be effective in anti-lung cancer therapy, but its molecular mechanism of action has not been clearly understood.
Purpose
In this study, we aimed to elucidate the possible molecular mechanism underlying the effect of RR against non-small cell lung cancer (NSCLC) by systems pharmacology.
Methods
The effects of RR on NSCLC were examined in Lewis lung carcinoma (LLC) tumor-bearing mice models. The possible molecular mechanism was unraveled by systems pharmacology, which includes pharmacokinetics evaluation, active compounds screening, target prediction and network analysis. Cell proliferation was examined by cell counting kit-8 (CCK-8) assay; cell apoptosis was detected by flow cytometry; protein and proinflammatory cytokines expression were evaluated by Western blot and qRT-PCR.
Results
In vivo, RR significantly inhibited the tumor growth and prolonged the survival of the tumor bearing mice. In silico, we identified 19 potential active molecules (e.g., salidroside and rhodiosin), 112 targets (e.g., COX-2 and AKT) and 27 pathways (e.g., PI3K/AKT signaling pathway and NF-κB signaling pathway) for RR. Additionally, targets analysis and networks construction further revealed that RR exerted anti-cancer effects by regulating apoptosis, angiogenesis and inflammation. In vitro, salidroside could significantly decrease expression of pro-angiogenic factors (e.g., VEGF and eNOS) and proinflammatory cytokines (e.g., COX-2, iNOS and TNF-α). Also, Bcl-2, an anti-apoptotic protein was decreased whereas Bax, a pro-apoptotic protein, was increased. Further flow cytometry analysis showed that salidroside could induce apoptosis in H1975 cells.
Conclusions
Mechanistically, the antitumor effect of RR on NSCLC was responsible for the synergy among anti-inflammatory, anti-angiogenic and pro-apoptotic.
Detailed knowledge on the spatiotemporal distribution of drugs or drug candidates in bio-tissues is of vital importance for the determination of their underlying mechanisms of action as well as evaluation of potential side effects. The present work involved the establishment of a matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) method for the visualization of distribution of salidroside, a bioactive ingredient of Rhodiola L. Crassulaceae, in multiple mouse tissue sections. 1,5-Diaminonaphthalene (1,5-DAN) hydrochloride was selected as the most suitable matrix by comparing the signal intensity produced by MALDI-MS analysis following cocrystallization of salidroside with different matrix candidates. The matrix deposition procedure was systematically optimized to obtain the best sensitivity as well as homogeneous matrix coverage on the tissue sections. The measurements were carried out in the negative reflectron ion mode (m/z 300–350 Da) with a spatial resolution of 200 μm. The proposed method demonstrated good performance with respect to specificity, linearity, and sensitivity, and the method exhibited a relatively reasonable run time. The approach was applied to determine the temporal-spatial location of salidroside in the kidney, liver, spleen, heart, lung, and brain following intravenous administration of the drug in mice. The results indicate that salidroside exhibited a heterogeneous distribution in the kidney and heart, and it can be rapidly eliminated by kidney 5 min after administration. The distribution information obtained by the in situ and label-free imaging technique proposed herein may benefit to our understanding of the activities and potential transient toxicities of salidroside in various organs.
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.
Cancer is a devastating disease that has claimed many lives. Natural bioactive agents from plants are gaining wide attention for their anticancer activities. Several studies have found that natural plant-based bioactive compounds can enhance the efficacy of chemotherapy, and in some cases ameliorate some of the side-effects of drugs used as chemotherapeutic agents. In this paper, we have reviewed the literature on the anticancer effects of four plant-based bioactive compounds namely, curcumin, myricetin, geraniin and tocotrienols (T3) to provide an overview on some of the key findings that are related to this effect. The molecular mechanisms through which the active compounds may exert their anticancer properties in cell and animal-based studies also discussed.
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.
Salidroside (SDS) is a phenylpropanoid glycoside isolated from Rhodiola rosea L. It exhibits multiple pharmacological properties in clinical medicine and has been commonly used in traditional Chinese medicine. The present study investigated the inhibitory effects of SDS on tumor invasion and migration, and the expression of metastasis‑related genes in highly metastatic hepatocellular carcinoma (HCC) cells (MHCC97H) in vitro. The underlying mechanisms of SDS on the tumor metastasis were also explored. SDS was found to significantly reduce wound closure areas and inhibit cell migration. In addition, SDS markedly inhibited the invasion of these cells into Matrigel‑coated membranes. SDS markedly downregulated the expression of Notch1, Snail, COX‑2, MMP‑2, MMP‑9 genes and upregulated the expression of E‑cadherin in a dose‑dependent manner. Furthermore, SDS inhibited the expression of the Notch signaling target genes, Hey1, Hes1 and Hes5. On the whole, the findings of this study suggest that SDS inhibits HCC cell metastasis by modulating the activity of the Notch1 signaling pathway.
Over the past two decades, natural remedies have been growing in popularity in the USA and worldwide. Given the limitations of current treatments for depression, natural medications as well as other complementary therapies represent for many a beneficial alternative to registered medications, particularly in cases of limited efficacy and/or side effects. This chapter will review several popular natural remedies often used in the treatment of depression. Specific remedies covered include St. John’s wort (SJW), S-adenosyl-L-methionine (SAMe), omega-3 fatty acids, rhodiola, and some less-known ones. We will provide some historical and socioeconomic perspectives on treatment with natural products, including present-day limitations to the systematic study of these remedies. We will examine the published research data from efficacy studies and discuss potential mechanisms of antidepressant action and specific safety considerations for each. Evidence for these remedies is varied in quantity and quality, and many questions remain unanswered with regard to their place in the psychopharmacological armamentarium. Clinicians who read this chapter will develop a good sense of how to apply these remedies in clinical practice safely.
Background:
Misuse of synthetic antibiotics in livestock leads to the transfer of antibiotic resistant pathogens into humans and deposits toxic residues in meat and milk. There is therefore an urgent need for safe and viable alternative approaches to improve the nutrition and wellbeing of farm animals. An alternative source that has been widely exploited is Traditional Chinese Herbal Medicine (TCHM). These herbs contain several but less toxic bioactive compounds which are generally regarded as biodegradable. Recently, advances in the knowledge of the importance of TCHM have led to a rapid increase in its production and hence, increasing the amount of by-products generated. Such by-products have become a serious environmental challenge because producers regard them as industrial waste and discard them directly. This review summarizes scientific findings on the bioactive compounds in TCHM and TCHM by-products, discusses functional dietary patterns and outlines challenges that may hinder full utilization of TCHM by-products in animal production.
Methods:
Information for this review was obtained through scientific databases and websites such as Pubmed and Google scholar from 2004 to 2017 using experimental studies on bioactive compounds in TCHM and their effects in animal production.
Results:
Studies have shown that TCHM by-products contain high amounts of bioactive compounds which confer several nutritional and health benefits to animals and thus could be incorporated as feed additives.
Conclusion:
The findings for this review indicate that TCHM by-products apart from being a good alternative for synthetic antibiotics could also minimize the current environmental challenges associated with its disposal.
L'orpin rose, plus souvent rencontré sous son nom scientifique, en raison de son utilisation internationale : Rhodiola rosea, est une plante herbacée qui appartient à la famille des Crassulacées.Aujourd'hui, il est classé comme une plante adaptogène au même titre que leGinseng.La composition chimique comprend de nombreuses molécules originales, retrouvéesuniquement dans cette plante.Cette plante a fait l'objet de nombreuses études en Russie, Géorgie, Bulgarie, Etats-Unis, Suisse, Norvège, Finlande, Japon, Chine. Elle est peu étudiée et mal connue en France.L'orpin rose aurait un effet adaptogène, un effet sur les capacités de travail, un effet sur le cerveau et l'état psychique, un effet endocrinien et sur la reproduction, un effet anticarcinogène, un effet hépatoprotecteur, un effet antioxydant et un effet antimicrobien.La racine de l'orpin rose est surtout utilisée aujourd'hui comme complément alimentaire, pour ses propriétés antistress et antifatigue.Plusieurs laboratoires français ont mis sur le marché des compléments alimentaires à base de Rhodiola rosea.A une époque où les méfaits du stress sur la santé sont de plus en plus reconnus, cette plante adaptogène trouvera naturellement sa place dans nos pharmacies.
Various Rhodiola rosea organs and tissues from in vitro culture were studied in two areas: searching for the biological active four phenolic compounds and measurement of antioxidant activity of dry residues of EtOH-extracts soluble in PBS using chemiluminescence method. For phytochemical investigation HPLC method was used. Salidroside was typical for organs of intact plant, rosavin for roots of different origin and shoots of intact plants, triandrin was more typical for tissue cultured in vitro, but it was found in all studied samples. Caffeic acid was detected mainly in green and yellow lines of callus, less in other Rhodiola rosea plant material. The highest antioxidant activity showed the extract from 1,5-years-old callus of green and yellow line, which contained caffeic acid and triandrin. Further observations are in progress.
Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme which plays a role in the metabolism of proline-containing neuropeptides, e.g., vasopressin, substance P and thyrotropin-releasing hormone (TRH), which have been suggested to be involved in learning and memory processes. In our systematic screening for PEP inhibitors from traditional Chinese medicines, we found that MeOH extract from the underground part of Rhodiola sacra S. H. Fu shows significant inhibitory activity against PEP from Flavobacterium meningosepticum. Examination of the constituents of the extract resulted in the isolation of nineteen known compounds, identified as hydroquinone (1), 4-hydroxybenzoic acid (2), caffeic acid (3), 4-hydroxycinnamic acid (4), suberic acid (5), protocatechuic acid (6), gallic acid (7), (-)-epigallocatechin 3-O-gallate (8), 2-phenylethyl beta-D-glucopyranoside (9), 3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate (10), 2-phenylethyl alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside (11), sacranoside A (12), beta-D-glucopyranosyl 4-hydroxybenzoate (13), rhodiocyanoside A (14), rhodiooctanoside (15), sarmentosin (16), heterodendrin (17), arbutin (18) and 4-O-(beta-D-glucopyranosyl)-gallic acid (19). Among these, 1, 2, 5, 8-10, 13, 16, 18 and 19 have been isolated for the first time from R. sacra, among which 5, 9, 10, 13, 16, 18 and 19 have been isolated from Rhodiola plants for the first time. On the PEP inhibition, seven compounds (6-8, 10, 12, 18, 19) showed inhibition with an 1C50 of 27.8, 487, 1.47, 0.437, 348, 391 and 215 microM, respectively. The kinetic study of these inhibitors indicated that they are noncompetitive inhibitors, except for 6 which is a competitive inhibitor.
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.
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.
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.
Bioactivity-guided fractionation of a methanol extract from the leaves of Piper lanceaefolium resulted in the isolation of four new benzoic acid derivatives (1-4), together with taboganic acid, pinocembrin, and pinocembrin chalcone. Lanceaefolic acid methyl ester (3) and pinocembrin chalcone displayed activity against Candida albicans with a minimal inhibitory concentration value of 100 mug/mL in both cases.
Activity-guided fractionation of the 95% ethanol extract from the stem bark of Iryanthera megistophylla led to the isolation of two new compounds, named megislignan [2,3-dimethyl-4-(4-methoxyphenyl)-6-hydroxynaphthalene] (1) and megislactone [(2R,3R,4R)-3-hydroxy-4-methyl-2-(hexacos-17-enyl)butanolide] (2), along with seven known compounds, grandinolide (3), iryantherin K (4), iryantherin L (5), cinchonain I b (6), cinchonain I a (7), procyanidin B-2 (8), and cinchonain IIa (9). The structures of the new compounds were elucidated by spectral data interpretation. Isolates were evaluated for their antibacterial, antifungal, antiviral, and antiacetylcholinesterase activities.
Sudden cardiac death (SCD) or sudden coronary death, occurring in patients with unstable angina (angina at rest), myocardial ischemia with or without myocardial infarction (MI), and congestive heart failure (CHF), emerges as one of the most important challenges in cardiovascular medicine at present. Of the 1.5 million cases of myocardial infarction that occur each year in the U.S., about 540,000 patients will die and more than 300,000 of these will die before they reach a hospital, mostly due to ventricular fibrillation (VF) and/or SCD. About 4.8 million people alive in the U.S. have a history of myocardial infarction, angina pectoris, or both and are prime candidates for SCD. About 3 million people in the U.S. have congestive heart failure (CHF) and about 400,000 new cases are reported each year. One year mortality due to CHF is 33–58% and about 45% of the deaths are sudden. These patients were not those who had deleterious hemodynamic parameters whose demise could be predicted; they were those that died suddenly and unexpectedly of VF. Current pharmacological intervention in patients with a documented myocardial infarction with marketed antiarrhythmic agents has not reduced the overall mortality of SCD significantly. This suggests that an efficacious antiarrhythmic/antifibrillatory agent for the prevention of SCD does not exist at present and that there is an urgent need for such an agent.
It is shown that autonomic nervous system participates in the preventive antiarrhythmic effect ofRhodiola rosea. The effect of the preparation is presumably mediated through modulation of the sympathetic nervous system.
Oral administration ofRhodiola rosea extract to rats (3.5 ml/kg, 8 days) prevents reperfusion arrhythmias and elicits a protective effect in experiments on isolated
heart. Experiments with naloxone and ICI 174,864 suggest that the antiarrhythmic effect ofR. rosea extract is mediated through activation of μ-opiate receptors in the myocardium. The cardioprotective effect of this extract
is not associated with opiate receptors.
The acetone extract of the roots ofRhodiola sachalinensis has furnished six phenolic compounds which exhibited significant scavenging effects against DPPH free radical. The structures
of these compounds were identified and determined as gallic acid (1), (−)-epigallocatechin 3-O-gallate (2), kaempferol (3), kaempferol 7-O-α-L-rhamnopyranoside (4), herbacetin 7-O-α-L-rhamnopyranoside, (5) and rhodiolinin (6) by physico-chemical and spectral evidences.
The active-oxygen scavenging activity of 70 traditional herbal medicines used in China and Japan as nourishing tonics were evaluated by electron spin resonance (ESR) technique, in order to evaluate their effectiveness for anti-aging and to search for new active-oxygen scavengers from natural resources. Most of the 70 herbal medicines showed scavenging activity with various intensities. Areca catechu (methanol extract), Dendrobium plicatile (methanol extract), Juglans regia (water extract), Paeonia lactiflora (methanol extract), Psychotria serpens (water and methanol extracts), Rhodiola sacra (water and methanol extracts) and Uncaria rhynchophylla (water extract) especially showed strong scavenging activity against superoxide anion radical (*O2-), while J. regia (water and methanol extracts), Morus alba (water extract) and Schisandra chinensis (water extract) revealed strong scavenging activity against hydroxyl radical (HO*). In addition, the active-oxygen scavenging activities of 19 compounds isolated from R. sacra were also examined, and hydroquinone (1), caffeic acid (3), protocatechuic acid (6), gallic acid (7), (-)-epigallocatechin 3-O-gallate (8), 3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate (10), heterodendrin (17) and gallic acid 4-O-beta-D-glucopyranoside (19) were found to show mild or strong inhibitory activity against superoxide anion radical (*O2-), while 4-hydroxybenzoic acid (2), 3, 4-hydroxycinnamic acid (4), 6-8 and 19 inhibited hydroxyl radical (OH*). These active-oxygen scavengers may contribute, to different extents, to their anti-aging action.
The ability of prostate-specific antigen (PSA) to predict tumor volume and stage in patients with prostate cancer would be improved if factors regulating its production and clearance were better defined. A thorough understanding of the pharmacokinetics (regulation of production, metabolism, and excretion) of PSA has been precluded, however, by the absence of an in vivo animal model. The purposes of this study are to develop a murine model for evaluating PSA pharmacokinetics in vivo and to assess factors that influence PSA production in vitro. The human prostate cancer cell line, LNCaP, was chosen because it is androgen sensitive and PSA positive. Although LNCaP cells are usually nontumorigenic when inoculated s.c. in athymic mice, coinoculation of 1 x 10(6) LNCaP cells with 1 x 10(6) human bone fibroblasts reliably produces PSA-secreting carcinomas. This LNCaP model provides accurate correlation between tumor volume and serum PSA levels (r = 0.94) and demonstrates that tumor volume and androgens are codeterminants of circulating PSA levels. Following castration, serum PSA levels decrease rapidly up to 8-fold and increase up to 20-fold following androgen supplementation, without detectable castration-induced tumor cell death or concomitant changes in tumor volume. Serum PSA levels increase 0.24 ng/ml/mm3 of tumor, which is approximately 5-fold less than that estimated for humans. Most likely this reduced PSA index (PSA:tumor volume ratio) results from a 7-fold faster clearance of PSA in athymic mice than in humans; other than this shorter half-life, PSA elimination in the murine model appears similar to that in humans, with both following first-order kinetics characteristic of a two-compartment model. Interestingly, following prolonged growth (greater than 21 days) in castrate hosts, LNCaP tumors are capable of adapting to an androgen-deprived environment whereby LNCaP tumors regain the ability to secrete PSA in amounts similar to the precastrate state. In LNCaP cells, androgens increase PSA mRNA levels 4-fold in vivo and in vitro. PSA mRNA expression is also altered by various growth factors. Changes in PSA production induced by androgens and growth factors do not always parallel changes in LNCaP cell growth rate induced by these factors, suggesting that PSA production occurs independently of cell growth rate and may be influenced by various interrelated factors, including hormonal and stromal milieu. Observations from this murine model suggest that androgens and tumor volume are independent determinants of serum PSA levels and imply that decreases in circulating PSA following antiandrogen therapy may not always reflect a corresponding reduction in tumor volume.
Prostate cancer, the most prevalent cancer affecting men, frequently metastasizes to the axial skeleton where it produces osteoblastic lesions with growth rates often exceeding that of the primary tumor. To evaluate the role of tumor cell-host stromal interaction and stromal specific growth factors (GFs) in prostate cancer growth and progression, we coinoculated athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts s.c. LNCaP tumor formation was most consistently induced by human bone (MS) fibroblasts (62%), followed by embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney, or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. The human prostate component of these tumors was confirmed with immunohistochemical staining for prostate-specific antigen (PSA), Northern analysis for PSA expression, and Southern analysis for human repetitive Alu sequences. Elevations in serum PSA paralleled the histomorphological and biochemical findings. LNCaP and fibroblast cell-conditioned media (CM) was used to determine whether autocrine and paracrine mitogenic pathways exist between LNCaP and fibroblast cells in vitro, and various defined GFs were tested to identify possible active factors. Mitogenic assays revealed a 200-300% bidirectional stimulation between LNCaP and bone or prostate fibroblast-derived CM. Lung, normal rat kidney, and 3T3 fibroblast CM were not mitogenic for LNCaP cells. Among the purified GFs tested basic fibroblast growth factor (bFGF) was the most potent mitogen, stimulating LNCaP growth 180% in a concentration-dependent manner. Transforming growth factor alpha and epidermal growth factor were both minimally mitogenic. Coinoculation of LNCaP cells with a slowly absorbed matrix (Gelfoam) absorbed with bFGF or dialyzed and concentrated rUGM or MS CM was also capable of inducing LNCaP tumor formation in vivo. These observations illustrate that fibroblasts differentially modulate prostate cancer growth through the release of paracrine-mediated GFs, possibly including bFGF, and that tumor-stromal cell interactions play an important role in prostate cancer growth and progression.
In experiment on rats with Pliss lymphosarcoma (PLS) it was shown that partial hepatectomy (PHE), a course application of Rhodiola rosea extract (RRE) or combined effects inhibit the growth of tumors by 37, 39 and 59%, respectively, and that of metastases by 42, 50 and 75%. In combined treatment the process of hepatic regeneration was completed in earlier terms versus the animals which underwent PHE, and proliferative activity of the tumor and metastases decreased by 15 and 59%, respectively, judging by the degree of 3H-thymidine incorporation into DNA of these tissues. The assessment of clonogenic activity of PLS cells taken in the animals of this group, using the method of diffusion chambers, revealed a significant decrease in this index versus the rats which underwent PHE or which were given RRE (number of colonies per chamber being 4.8 +/- 0.5; 8.6 +/- 0.9; 5.7 +/- 0.6, respectively; in control 13.8 +/- 1.5). The assumption that these effects are determined by factors originating from the regenerating liver was confirmed in experiments with double-layer agar systems. Inhibition of colony-forming activity of PLS cells was the maximum in application of the hepatocytes of the rats which underwent a complex of effects, as a feeder, versus the hepatocytes taken in intact or hepatectomized animals, or the rats which were given RRE (number of colonies per plate well being 4.6 +/- 0.3; 15.7 +/- 1.6; 7.4 +/- 0.8; 8.7 +/- 0.9, respectively; in the control 25.6 +/- 6.5). In experiments on mice with Ehrlich adenocarcinoma, the factors isolated from the liver of animals subjected to PHE against a background of RRE administration and from the liver of mice which were given RRE only, as well as operated or intact ones, inhibited the tumor growth to 63, 38, 35 and 21%, respectively.
Polymer proanthocyanidin from Rhodiola semenovii named epihalochin was found to exhibit a pronounced antihypoxic effect in different models of hypoxia (hypoxic, cytotoxic and hemic), to relieve the hypoxic isolated heart contracture. Therapeutic doses of epihalochin produced a transient lowering of arterial pressure, decreased to a certain degree heart rate and lengthened the phases of cardiac contractions.
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.
The antimicrobial properties of some traditional Carrier herbal preparations were evaluated using an agar dilution method. Pitch preparations were screened against known human pathogens: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus fumigatus. The results indicated definite antimicrobial activity in the pitch preparations of Picea glauca and Pinus contorta and provide a starting point for pharmacognostic evaluation of these species. In addition, cytoxicity assays, to test the anticancer activity of methanolic extracts of Alnus incana and Shepherdia canadensis against mouse mastocytoma cells, were shown to be positive.
Two bioactive cyanoglycosides, rhodiocyanosides A and B, and two oligoglycosides, rhodioflavonoside [gossypetin 7-O-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranoside] and rhodiooctanoside [octyl alpha-L-arabinopyranosyl(1-->6) beta- D-glucopyranoside), 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 four known compounds: rhodioloside, n-hexyl beta-D-glucopyranoside, gossypetin 7-O-alpha-L-rhamnopyranoside, and tricetin. The chemical structures of new glycosides 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-2,4-dinitrophenyl IgE. Additionally, rhodiocyanoside A, the major constituent of this natural medicine, was also found to show antiallergic activity in a passive cutaneous anaphylaxis test in rat.
In order to screen potent inhibitors of tumor invasion and metastasis, we here devised a simple and reproducible in vitro assay for tumor invasion and migration. A conventional cell-counting assay using a Transwell chamber with a microporous membrane filter is troublesome and time-consuming, involving visually counting the cells under a microscope, and the invaded or migrated cells are sometimes distributed unevenly in predetermined fields on the lower surface of the filter. Therefore, it is difficult to evaluate the invasive and migratory abilities of tumor cells easily and quantitatively by the cell counting method. In the present study, crystal violet dye was used for staining the invaded cells and colorimetrically assessing the invasive ability per filter as an absorbance. In this crystal violet assay, tumor cell invasion into a reconstituted basement membrane Matrigel was proportional to both the cell number added into the chamber and the incubation period, and inversely proportional to the amount of Matrigel barrier on the upper surface of filter. The results obtained by this dye-uptake method were highly consistent with those of a conventional cell-counting assay. Using this crystal violet assay, the anti-invasive effect of doxorubicin (DOX) was detected more easily and found to be highly proportional to that by the conventional cell-counting method. We therefore applied this convenient assay method to screen anti-invasive and anti-metastatic compounds. As a result, caffeic acid was found to be more active in the inhibition of both tumor cell invasion and migration without showing direct cytotoxicity in vitro than other related compounds.
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%.
Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential.
Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme to play a role in metabolism of proline-containing neuropeptides, such as vasopressin, substance P and thyrotropin-releasing hormone (TRH), which were suggested to be involved with learning and memory processes. Then, specific inhibitor of PEP is expected to have antiamnesic effects, and thus we screened forty-six water- and methanol-extracts from crude drugs selected on the basis of traditional Chinese medicine theory, for Flavobacterium prolyl endopeptidase inhibition. Among them, the water-extracts of Rhodiola sacra (IC50, 0.77 microgram/ml) and the methanol-extracts of Lycopodium clavatum (IC50, 1.3 micrograms/ml), Paeonia lactiflora var. trichocarpa (IC50, 5.7 micrograms/ml), Paeonia veitchii (IC50, 2.4 micrograms/ml) and Rhodiola sacra (IC50, 0.67 microgram/ml) showed strong inhibitory activity. In addition, we also examined the PEP inhibitory activity of eleven compounds from Salvia deserta, and found that in addition to a catechol group alpha-hydroxy-para-quinone group may be related to the PEP inhibition.
A reversed-phase high performance liquid chromatographic method was developed to determine salidroside and tyrosol simultaneously in the Rhodiola rosea. The optimum condition was Nova-Pak C18 as stationary phase, 6.5% methanol in water as mobile phase and detection at UV 225 nm. The identification was carried out by comparing the retention time and IC/MS spectrum of the relevant peaks with those of isolated standards. The contents of salidroside and tyrosol in the samples gathered from various area in China were ranged over 1.3-11.1 mg/g and 0.3-2.2 mg/g, respectively.
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.
Rhodiola rosea is a popular plant in traditional medical systems in Eastern Europe and Asian with a reputation for stimulating the nervous system, decreasing depression, enhancing work performance, eliminating fatigue, and preventing high altitude sickness. Rhodiola rosea has been categorized as an adaptogen by Russian researchers due to its observed ability to increase resistance to a variety of chemical, biological, and physical stressors. Its claimed benefits include antidepressant, anticancer, cardioprotective, and central nervous system enhancement. Research also indicates great utility in asthenic conditions (decline in work performance, sleep difficulties, poor appetite, irritability, hypertension, headaches, and fatigue) developing subsequent to intense physical or intellectual strain. The adaptogenic, cardiopulmonary protective, and central nervous system activities of Rhodiola rosea have been attributed primarily to its ability to influence levels and activity of monoamines and opioid peptides such as beta-endorphins.
Bioactivity-guided fractionation of a methanol extract from the leaves of Piper lanceaefolium resulted in the isolation of four new benzoic acid derivatives (1-4), together with taboganic acid, pinocembrin, and pinocembrin chalcone. Lanceaefolic acid methyl ester (3) and pinocembrin chalcone displayed activity against Candida albicans with a minimal inhibitory concentration value of 100 microg/mL in both cases.
The renin-angiotensin system has long been recognized as crucial factor in the regulation of the systemic blood pressure and renal electrolyte homeostasis. Numerous studies have demonstrated the presence of a local renin-angiotensin system in a variety of organs. A recent study of the pancreatic renin-angiotensin system showed that chronic hypoxia significantly increased the mRNA expression for angiotensinogen II receptor subtypes AT1b and AT2. The activation of the renin-angiotensin system may play an important role in cellular pathophysiological processes. Angiotensin II enhances the formation of reactive oxygen species via the activation of xanthine oxidase or NAD(P)H oxidase. The reactive oxygen species can cause oxidative damage in the pancreas and other tissues either directly or indirectly via the formation of other radicals such as reactive nitrogen species. Rhodiola therapy may protect hypoxia-induced pancreatic injury in two ways. It prevents hypoxia-induced biological changes by increasing intracellular oxygen diffusion and efficiency of oxygen utilization. Alternatively, it reduces hypoxia-induced oxidative damage by its antioxidant activities. Additional experimental data are required to fully elucidate the mode of action of this herbal drug.
Activity-guided fractionation of the 95% ethanol extract from the stem bark of Iryanthera megistophylla led to the isolation of two new compounds, named megislignan [2,3-dimethyl-4-(4-methoxyphenyl)-6-hydroxynaphthalene] (1) and megislactone [(2R,3R,4R)-3-hydroxy-4-methyl-2-(hexacos-17-enyl)butanolide] (2), along with seven known compounds, grandinolide (3), iryantherin K (4), iryantherin L (5), cinchonain I b (6), cinchonain I a (7), procyanidin B-2 (8), and cinchonain IIa (9). The structures of the new compounds were elucidated by spectral data interpretation. Isolates were evaluated for their antibacterial, antifungal, antiviral, and antiacetylcholinesterase activities.
A novel gallotannin, crenulatin ( 7), has been isolated from RHODIOLA CRENULATA. The structure was elucidated by spectral analyses (including 2D-NMR spectral measurements) and chemical methods. Also six known polyphenols have been isolated and identified.
Flavonoids of the above-ground part of Rhodiola rosea. II. Structure of novel glycosides of herbacetin and gossypetin
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Flavonoids of the above-ground part of Rhodiola rosea. II.
Structure of novel glycosides of herbacetin and gossypetin.
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