Rhodiola crenulata extract for prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled, crossover trial.
ABSTRACT: BACKGROUND:Rhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double-blind, placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention. METHODS:Healthy adult volunteers were randomized to 2 treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering, before crossing over to the alternate treatment after a 3-month wash-out period. Participants ascended rapidly from 250 m to 3421 m on two separate occasions: December 2010 and April 2011. The primary outcome measure was the incidence of acute mountain sickness, as defined by a Lake Louise score???3, with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping. RESULTS:One hundred and two participants completed the trial. There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups (all 60.8%; adjusted odds ratio (AOR) =?1.02, 95% confidence interval (CI) =?0.69-1.52). The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3% vs. 29.4% (AOR?=?1.42, 95% CI?=?0.90-2.25). CONCLUSIONS:R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo. TRIAL REGISTRATION:ClinicalTrials.gov NCT01536288.
Project description:OBJECTIVES: To assess the efficacy of three different daily doses of acetazolamide in the prevention of acute mountain sickness and to determine the lowest effective dose. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline and Embase along with a hand search of selected bibliographies. No language restrictions were applied. STUDY SELECTION: Randomised controlled trials assessing the use of acetazolamide at 250 mg, 500 mg, or 750 mg daily versus placebo in adults as a drug intervention for the prophylaxis of acute mountain sickness. Included studies were required to state the administered dose of acetazolamide and to randomise participants before ascent to either acetazolamide or placebo. Two reviewers independently carried out the selection process. DATA EXTRACTION: Two reviewers extracted data concerning study methods, pharmacological intervention with acetazolamide, method of assessment of acute mountain sickness, and event rates in both control and intervention groups, which were verified and analysed by the review team collaboratively. DATA SYNTHESIS: 11 studies (with 12 interventions arms) were included in the review. Acetazolamide at doses of 250 mg, 500 mg, and 750 mg were all effective in preventing acute mountain sickness above 3000 m, with a combined odds ratio of 0.36 (95% confidence interval 0.28 to 0.46). At a dose of 250 mg daily the number needed to treat for acetazolamide to prevent acute mountain sickness was 6 (95% confidence interval 5 to 11). Heterogeneity ranged from I(2)=0% (500 mg subgroup) to I(2)=44% (750 mg subgroup). CONCLUSIONS: Acetazolamide in doses of 250 mg, 500 mg, and 750 mg daily are all more effective than placebo for preventing acute mountain sickness. Acetazolamide 250 mg daily is the lowest effective dose to prevent acute mountain sickness for which evidence is available.
Project description:The roots and rhizomes of Rhodiola crenulata and R. rosea have been used worldwide as adaptogens for hundreds of years. However, rapid growth in demand has resulted in merchants using other species of Rhodiola as adulterants. Here, we surveyed 518 individuals representing 47 of the 55 species in the genus, including 253?R. crenulata individuals from 16 populations and 98?R. rosea individuals from 11 populations, to evaluate the utility of the internal transcribed spacer 2 (ITS2) barcode for identification of Rhodiola species. We detected six haplotypes in R. crenulata and only one haplotype in R. rosea. An obvious overlap between intra- and inter-specific distance was detected, and the authentication efficacy of ITS2, which was assessed by BLAST1, a nearest distance method, and a tree test, was much lower than in other groups. However, R. crenulata and R. rosea could be exactly identified. Analysis showed that the secondary structure of ITS2 differs in R. crenulata and its closest relatives. Our results demonstrated that both a mini barcode from ITS2 and the structure of ITS2 are effective markers for the identification of R. crenulata and R. rosea. This study represents the most comprehensive database of ITS2 barcodes in Rhodiola to date and will be useful in Rhodiola species identification.
Project description:Rhodiola crenulata, a well-known medicinal Tibetan herb, is mainly grown in high-altitude regions of the Tibet, Yunnan, and Sichuan provinces in China. In the past few years, increasing numbers of studies have been published on the potential pharmacological activities of R. crenulata, strengthening our understanding into its putitive active ingredient composition, pharmacological activity, and mechanism of action. These findings also provide strong evidence supporting the important medicinal and economical value of R. crenulata. Consequently, some Rhodiola species are becoming endangered because of overexploitation and environmental destruction. However, little is known about the genetic and genomic information of any Rhodiola species. Here we report the first draft assembly ofthe R. crenulata genome, which was 344.5 Mb (25.7 Mb Ns), accounting for 82% of the estimated genome size, with a scaffold N50 length of 144.7 kb and a contig N50 length of 25.4 kb. The R. crenulata genome is not only highly heterozygous but also highly repetitive, with ratios of 1.12% and 66.15%, respectively, based on the k-mer analysis. Furthermore, 226.6 Mb of transposable elements were detected, of which 77.03% were long terminal repeats. In total, 31 517 protein-coding genes were identified, capturing 86.72% of expected plant genes in BUSCO. Additionally, 79.73% of protein-coding genes were functionally annotated. R. crenulata is an important medicinal plant and also a potentially interesting model species for studying the adaptability of Rhodiola species to extreme environments. The genomic sequences of R. crenulata will be useful for understanding the evolutionary mechanism of the stress resistance gene and the biosynthesis pathways of the different medicinal ingredients, for example, salidroside in R. crenulata.
Project description:Rhodiola species have a long history of use in traditional medicine in Asian and European countries and have been considered to possess resistance to the challenges presented by extreme altitudes. However, the influence of different Rhodiola species on quality is unclear, as well as the influence of altitude on phytochemicals. In this study, the phenolic components and antioxidant abilities of two major Rhodiola species are compared, namely Rhodiolacrenulata and Rhodiola rosea, and the metabolomes of Rhodiolacrenulata from two representative elevations of 2907 and 5116 m are analyzed using a UPLC-QqQ-MS-based metabolomics approach. The results show that the phenolic components and antioxidant activities of Rhodiolacrenulata are higher than those of Rhodiola rosea, and that these effects in the two species are positively correlated with elevation. Here, 408 metabolites are identified, of which 178 differential metabolites (128 upregulated versus 50 downregulated) and 19 biomarkers are determined in Rhodiola crenulata. Further analysis of these differential metabolites showed a significant upregulation of flavonoids, featuring glucosides, the enhancement of the phenylpropanoid pathway, and the downregulation of hydrolyzed tannins in Rhodiola crenulata as elevation increased. Besides, the amino acids of differential metabolites were all upregulated as the altitude increased. Our results contribute to further exploring the Rhodiola species and providing new insights into the Rhodiola crenulata phytochemical response to elevation.
Project description:Rhodiola has long been used as a traditional medicine to increase resistance to physical stress in humans in Tibet. The current study was designed to investigate whether Rhodiola crenulata (R. crenulata) could alleviate the negative effects of hypoxia on broiler chickens reared in Tibet Plateau. The effect of supplementing crushed roots of R. crenulata on production performance, health and intestinal morphology in commercial male broilers was investigated. Dietary treatments included CTL (basal diet), Low-R (basal diet + 0.5% R. crenulata) and High-R (basal diet + 1.5% R. crenulata). In comparison with broilers fed the control diet, Low-R had no effect on production performance while High-R significantly decreased average daily feed intake at d 14, 28 and 42, body weight at d 28 and 42 and gut development. Ascites induced mortality did not differ among treatments. Nevertheless Low-R significantly reduced non-ascites induced mortality and total mortality compared with broilers fed CTL and High-R diets. Broilers fed the High-R diet had significantly increased blood red blood cell counts and hemoglobin levels at 28 d compared with other treatments. Our results suggest that supplementation with Rhodiola might reduce the effects of hypoxia on broilers and consequently decrease mortality rate.
Project description:Rhodiola species are antioxidative, salubrious plants that are known to inhibit oxidative stress induced by ultraviolet and ?-radiation in epidermal keratinocytes. As certain phytochemicals activate aryl hydrocarbon receptors (AHR) or OVO-like 1 (OVOL1) to upregulate the expression of epidermal barrier proteins such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL), we investigated such regulation by Rhodiola crenulata root extract (RCE). We demonstrated that RCE induced FLG and LOR upregulation in an AHR-OVOL1-dependent fashion. However, RCE-mediated IVL upregulation was AHR-dependent but OVOL1-independent. Coordinated upregulation of skin barrier proteins by RCE via AHR may be beneficial in the management of barrier-disrupted inflammatory skin diseases such as atopic dermatitis.
Project description:BACKGROUND:Quaternary climatic oscillations had tremendous effects on the current distribution of species. Here, we aim to elucidate the glacial history of Rhodiola crenulata, a perennial herb almost exclusively restricted to rock crevices on mountain peaks, and to test whether the nunatak or massif de refuge hypotheses could explain its distribution pattern. RESULTS:Six haplotypes and six ribotypes were detected in the cpDNA data set and the ITS data set, respectively. The divergence of R. crenulata and its closest relatives was dated have occurred ca. 0.65 Mya, during the Naynayxungla glaciation on the QTP. Mismatch distribution analysis suggested that the species experienced a range expansion around 0.31 Mya. Populations with high genetic and haplotype diversity were found on the QTP platform as well in the Hengduan Mountains. The ecological niche modeling results showed that there were suitable habitats on both the QTP platform and in the Hengduan Mountains during the LGM. CONCLUSION:Our results support a scenario that both nunataks and the massif de refuge hypotheses could explain the distribution of R. crenulata. We also confirmed that Quaternary climatic oscillations could promote plant speciation in some circumstances. This study adds to a growing body of evidence suggesting that the QTP plant lineages exhibited diverse reactions to the Quaternary climatic oscillations.
Project description:The root extract of Rhodiola rosea has historically been used in Europe and Asia as an adaptogen, and similar to ginseng and Shisandra, shown to display numerous health benefits in humans, such as decreasing fatigue and anxiety while improving mood, memory, and stamina. A similar extract in the Rhodiola family, Rhodiola crenulata, has previously been shown to confer positive effects on the gut homeostasis of the fruit fly, Drosophila melanogaster. Although, R. rosea has been shown to extend lifespan of many organisms such as fruit flies, worms and yeast, its anti-aging mechanism remains uncertain. Using D. melanogaster as our model system, the purpose of this work was to examine whether the anti-aging properties of R. rosea are due to its impact on the microbial composition of the fly gut.Rhodiola rosea treatment significantly increased the abundance of Acetobacter, while subsequently decreasing the abundance of Lactobacillales of the fly gut at 10 and 40 days of age. Additionally, supplementation of the extract decreased the total culturable bacterial load of the fly gut, while increasing the overall quantifiable bacterial load. The extract did not display any antimicrobial activity when disk diffusion tests were performed on bacteria belonging to Microbacterium, Bacillus, and Lactococcus.Under standard and conventional rearing conditions, supplementation of R. rosea significantly alters the microbial community of the fly gut, but without any general antibacterial activity. Further studies should investigate whether R. rosea impacts the gut immunity across multiple animal models and ages.
Project description:BACKGROUND:Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. METHODS/DESIGN:D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25?mg dexamethasone or normal saline placebo intravenously after 8?h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. DISCUSSION:MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS. TRIAL REGISTRATION:Clinicaltrials.gov, NCT03341676 . Registered on 14 November 2017.
Project description:The fast developing international trade of products based on traditional knowledge and their value chains has become an important aspect of the ethnopharmacological debate. The structure and diversity of value chains and their impact on the phytochemical composition of herbal medicinal products, as well as the underlying government policies and regulations, have been overlooked in the debate about quality problems in transnational trade. Rhodiola species, including Rhodiola rosea L. and Rhodiola crenulata (Hook. f. & Thomson) H. Ohba, are used as traditional herbal medicines. Faced with resource depletion and environment destruction, R. rosea and R. crenulata are becoming endangered, making them more economically valuable to collectors and middlemen, and also increasing the risk of adulteration and low quality. Rhodiola products have been subject to adulteration and we recently assessed 39 commercial products for their composition and quality. However, the range of Rhodiola species potentially implicated has not been assessed. Also, the ability of selected analytical techniques in differentiating these species is not known yet. Using a strategy previously developed by our group, we compare the phytochemical differences among Rhodiola raw materials available on the market to provide a practical method for the identification of different Rhodiola species from Europe and Asia and the detection of potential adulterants. Nuclear magnetic resonance spectroscopy coupled with multivariate analysis software and high performance thin layer chromatography techniques were used to analyse the samples. Rosavin and rosarin were mainly present in R. rosea but also in Rosea sachalinensis Borris. 30% of the Rhodiola samples purchased from the Chinese market were adulterated by other Rhodiola spp. The utilization of a combined platform based on (1)H-NMR and HPTLC methods resulted in an integrated analysis of different Rhodiola species. We identified adulteration at the earliest stage of the value chains, i.e., during collection as a key problem involving several species. This project also highlights the need to further study the links between producers and consumers in national and trans-national trade.