Rhodiola (Stress)

BACKGROUND: Chronic stress is detrimental to the maintenance of the main response system - the hypothalamic-pituitary-adrenal (HPA) axis. The current study aimed to investigate the efficacy of two plant-based adaptogens, a formula containing Rhodiola, holy basil and Schisandra chinensis (VL-G-A57) and a full-spectrum ashwagandha (VL-G-E12), on stress and related symptoms in individuals with high stress. MATERIALS AND METHODS: The 60-day randomized, double-blind, placebo-controlled clinical study included individuals aged between 18 to 65 years with a body mass index (BMI) of 18 to 29.9 kg/m2. One hundred eighty-six participants were randomized to one of the adaptogens, VL-G-A57 or VL-G-E12, or to placebo. The primary outcome was a reduction in stress levels. Secondary outcomes were changes in sleep quality, fatigue, restorative sleep, mental alertness, mood dysregulation, and anxiety. A priori power analysis determined the required sample size. Efficacy was assessed by comparing mean changes in the primary endpoint at days 30 and 60 using ANCOVA, with baseline values as covariates. Dunnett's post hoc test identified significant differences versus placebo, and within-group changes were evaluated using paired t-tests. Normality was assessed visually and via Shapiro-Wilk/Kolmogorov-Smirnov tests as needed. Secondary outcomes were analyzed similarly. Analyses were conducted using R (v4.0.5) and XLSTAT (v2021.3.1). RESULTS: At day 60, both VL-G-A57 and VL-G-E12 significantly reduced Perceived Stress Scale (PSS) scores compared to placebo (p < 0.0001). Sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), improved significantly in both adaptogen groups (VL-G-A57: p = 0.0008, VL-G-E12: p < 0.0001). This corresponded well with the Restorative Sleep Questionnaire-Weekly (RSQ-W) results in the two IP arms when compared with placebo (p < 0.0001). Additionally, mood dysregulation (VL-G-A57: p = 0.0454), anxiety (VL-G-A57: p = 0.0004, VL-G-E12: p = 0.0015), and stress levels (VL-G-A57-VL-G-E12: p < 0.0001) showed significant improvements compared to placebo. No differences in mental alertness were observed. CONCLUSION: The study concluded that both VL-G-A5

BACKGROUND: Rhodiola rosea extract is purported to improve physical performance and support resilience to stress. Salidroside is considered to be one of the main constituents responsible for the ergogenic actions of R. rosea. However, R. rosea extract contains relatively little salidroside and cultivation of R. rosea is challenging as it is mainly found in high-altitude, cold regions. Additionally, the R. rosea plant is subject to conservation concerns because of its growing popularity. The purpose of this exploratory study was to evaluate the short-term effects of pure, biosynthetic salidroside supplementation on exercise performance, mood state, and markers of inflammation and muscle damage in healthy active young adults. METHODS: Fifty participants (30 M, 20F; 21 ± 4 yrs; 173 ± 8 cm; 74 ± 13 kg) were randomly assigned to either salidroside (60 mg/day for 16 days) or placebo supplementation and underwent peak oxygen uptake (VO2 peak), intermittent time-to-exhaustion (TTE), and local muscular endurance assessments, along with mood state evaluations using the Profile of Mood States (POMS). Blood samples were analyzed for erythropoietin, myoglobin, creatine kinase-MM, and C-reactive protein. RESULTS: Salidroside supplementation enhanced overall percent predicted oxygen uptake during high-intensity intermittent exercise (p < 0.01). An increase in serum myoglobin was observed 24 hours following exercise in the placebo group (p = 0.02) compared with baseline whereas no statistically significant increase was observed for the salidroside group indicating reduced exercise-induced muscle damage. Placebo group experienced a decrease in number of intervals performed during the TTE test (p = 0.03), and a decrease in friendliness (p < 0.01) and an increase in fatigue-inertia (p < 0.01) as reported by POMS. The salidroside group exhibited stable mood states and maintained performance levels during the time-to-exhaustion test. CONCLUSION: Salidroside supplementation may enhance oxygen utilization and mitigate exercise-induced muscle damage and fatigue, warranting further research on its long-term effects and potential as an adaptogen for active individuals.

Yu Liu, Zhengyang Zhang, Yongting Luo, Peng An, Jingyi Qi, Xu Zhang, Shuaishuai Zhou, Yongzhi Li, Chong Xu, Junjie Luo, and Jiaping Wang. Product of traditional Chinese medicine longgui yangxinwan protects the human body from altitude sickness damage by reducing oxidative stress and preventing mitochondrial dysfunction. High Alt Med Biol. 26:20-29, 2025. Background: Plateau reaction, caused by high-altitude exposure, results in symptoms like headaches, dyspnea, palpitations, fatigue, shortness of breath, and insomnia due to reduced oxygen levels. Mitochondria are crucial for high-altitude acclimatization as they regulate oxygen metabolism and cellular energy, reducing oxidative stress and maintaining bodily functions. Methods: The study participants were randomly divided into placebo group, Rhodiola group and longgui yangxinwan (Original name: taikong yangxinwan) group, with 20 people in each group. Three groups of subjects were sampled at three time points (PI: pre-intervention; P-D1: high-altitude day 1; P-D7: high-altitude day 7), and blood pressure, blood oxygen, heart rate, hemoglobin, and red blood cell count were measured. The ATP content, mitochondrial DNA copy number, expression of mitochondria-related genes, reactive oxygen species (ROS), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels, and mitochondrial morphology were measured in blood at each time point. Results: Our study results demonstrate that longgui yangxinwan keeps the selected human physiological indicators stable and prevents mitochondrial dysfunction in the high altitude. Mechanically, longgui yangxinwan decreases the level of ROS in human serum, whereas increases the activity of the antioxidant enzyme GSH-PX. At high-altitude day 1 (P-D1) and high-altitude day 7 (P-D7), ROS in the placebo group were 1.5 and 2.2-fold higher than those of the longgui yangxinwan group, respectively. In addition, longgui yangxinwan enhances ATP production capacity, restores the levels of mitochondrial respiratory chain complexes, and effectively maintains mitochondrial morphology and integrity. At P-D1 and P-D7, the ATP levels in the longgui yangxinwan group were 19-fold and 26-fold higher th

Premenstrual syndrome is a common disorder in women of reproductive age characterized by a variety of cyclical symptoms with a great impact on their lifestyle. Available pharmacological options include both antidepressants and oral contraceptives, both of which have side effects, are expensive and not always effective. Vitamins, minerals and plant extracts have been proven to alleviate the symptomatology of the premenstrual syndrome. For this reason, the purpose of this study was to test the effectiveness of a commercial phytotherapeutic dietary supplement (PREMEN-CALM®: γ-aminobutyric acid, Rhodiola rosea L., Vitex agnus-castus, vitamin B6 and melatonin) as an alternative treatment for this condition. A randomized, double-blind, and placebo-controlled pilot study was performed. Participants (n = 42) were assessed before and after 3 months of taking the supplement (n = 21) or the placebo (n = 21). Outcome measures include antioxidant and inflammatory biomarkers, body composition, subjective sleep quality, mood state profile, quality of life, and certain characteristics of the menstrual cycle. The within-group analysis revealed a significant improvement in the total antioxidant status (1.49 ± 0.34 vs reference value 1, p = 0.002), mood state profile (p = 0.02), and affective symptoms (p = 0.01) in the women receiving the commercial phytotherapeutic dietary supplement PREMEN-CALM®. On the contrary, the between-group analysis showed no statistical differences, suggesting a plausible placebo effect. The phytotherapeutic supplement PREMEN-CALM® might be effective in treating or alleviating the symptoms of the premenstrual syndrome without adverse events. Integrative medicine approaches in the clinical practice may help improve the health of women suffering from this and other gynecological conditions.

The effect of a combination of magnesium, vitamins B6, B9, B12, rhodiola and green tea/L-theanine (Mg-Teadiola) on stress was evaluated in chronically stressed, otherwise healthy individuals. Effects on stress-related quality-of-life parameters (sleep and perception of pain) were also explored. Adults with stress for ≥1 month, scoring ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire, were randomized (1:1) to receive oral Mg-Teadiola (n = 49) or a placebo (n = 51), for 28 days, with a follow-up assessment on Day 56 (NCT04391452). The primary endpoint was the change in the DASS-42 stress score from baseline to Day 28 with Mg-Teadiola versus placebo. The DASS-42 stress scores significantly decreased from baseline to Day 28 with Mg-Teadiola versus placebo (effect size, 0.29; 95% CI [0.01, 0.57]; p = 0.04). Similar reductions were observed on Day 14 (p = 0.006) and Day 56 (p = 0.02). A significant reduction in sensitivity to cold pain (p = 0.01) and a trend for lower sensitivity to warm pain was observed (p = 0.06) on Day 28. Improvements in daytime dysfunction due to sleepiness (Pittsburgh Sleep Quality Index-7 component score) were reported on Day 28, and were significant on Day 56 (p < 0.001). Mg-Teadiola is effective in managing stress in otherwise healthy individuals. Its beneficial effects on sleep and pain perception need further investigation.

BACKGROUND: Magnesium (Mg), green tea and rhodiola extracts have, in isolation, been shown to possess stress and anxiety relieving effects. Green tea and rhodiola have been shown to modulate EEG oscillatory brain activity associated with relaxation and stress perception. The combined capacity of these ingredients to confer protective effects under conditions of acute stress has yet to be examined. We tested the hypothesis that a combination of Mg (with B vitamins) + green tea + rhodiola would acutely moderate the effects of stress exposure. METHODS: A double blind, randomised, placebo controlled, parallel group design was employed (Clinicaltrials.gov:NCT03262376; 25/0817). One hundred moderately stressed adults received oral supplementation of either (i) Mg + B vitamins + green tea + rhodiola; (ii) Mg + B vitamins + rhodiola; (iii) Mg + B vitamins + green tea; or (iv) placebo. After supplementation participants were exposed to the Trier Social Stress Test. The effects of the study treatments on electroencephalogram (EEG) resting state alpha and theta, subjective state/mood, blood pressure, heart rate variability and salivary cortisol responses after acute stress exposure were assessed. RESULTS: The combined treatment significantly increased EEG resting state theta (p < .02) - considered indicative of a relaxed, alert state, attenuated subjective stress, anxiety and mood disturbance, and heightened subjective and autonomic arousal (p < .05). CONCLUSIONS: Mg, B vitamins, rhodiola and green tea extracts are a promising combination of ingredients that may enhance coping capacity and offer protection from the negative effects of stress exposure.Trial registration: ClinicalTrials.gov identifier: NCT03262376.

BACKGROUND: Various plant extracts have been suggested to be used as auxiliary agents in chemotherapy considering their anti-proliferative effect on cancer cells. However, recent reports reveal that plant extracts may function as inducers of autophagy of cancer cells. In general, autophagy confers survival advantage for cells responding to stress conditions, thus representing an important mechanism for chemo-resistance. This study was aimed to investigate the effectiveness of combined use of Salidroside (Sal, a phenylpropanoid glycosides from Rhodiola rosea L) with anti-tumor agents against colorectal cancer (CRC) cells, and moreover to evaluate the potential role of autophagy in the combined therapy. METHODS: CRC cells, HCT-116, were incubated with Sal alone or in combination with conventional chemotherapy agents including oxaliplatin (OXA), 5-fluorouracil (5-FU) and Doxorubicin (ADM). Cell proliferative characteristics were evaluated by cell viability and apoptosis rate. The protein expression was assessed by Immunofluorescent and Western blot assays. RESULTS: Sal, alone or in combination with anti-tumor agents, increased expression of autophagic biomarkers, including LC3B and Becline-1, suggesting an autophagy induction. Except for the up-regulation of p-AMPK, p-mTOR, p-NF-κB (p65), TGF-β, p-JAK2 and p-STAT3 were down-regulated by Sal. Because autophagy is positively correlated with the activation of AMPK/mTOR, NF-κB, TGFβ1 and JAK2/STAT3 cascades, the autophagy induced by Sal may associate with AMPK activation. Indeed, blockage of AMPK signaling via Compound C or AMPK knockdown inhibited the autophagy. The blockage of AMPK signaling or a direct inhibition of autophagy via 3-MA increased effectiveness of combined use of Sal with anti-tumor agents against CRC. CONCLUSIONS: Inhibition of autophagy enhances synergistic effects of Sal and anti-tumor agents against colorectal cancer. This study provides experimental evidence and theoretical reference for improvement of a novel chemotherapy treatment protocol. Salidroside, a scavenger of ROS, enhances the radioprotective effect of Ex-RAD® via a p53-dependent apoptotic pathway. Feng T(1), Wang L(1), Zhou N(1), Liu

OBJECTIVE: Rhodiola rosea (Russian Rhodiola/Golden Root) is a high mountain plant from the arctic regions of Europe and Asia which has the active substance phenylpropanoide. It has sedative, anti-depressive, drive-enhancing and stress-modulated properties stimulating the distribution of dopamine and serotonin; in combination with other drugs, an increase of side effects and risk profile has to be expected. METHODS: A case report is presented in order to illustrate the interaction between Rhodiola rosea and antidepressants. RESULTS: We report the case of a 68-year-old female patient with recurrent moderate depressive disorder with somatic syndrome (ICD-10 F33.11) who developed vegetative syndrome, restlessness feeling and trembling since she began to ingest Rhodiola rosea in addition to paroxetine. CONCLUSIONS: Prescribing Rhodiola rosea with paroxetine, pharmacokinetic and -dynamic interactions have to be assumed. The symptoms of the patient can be interpreted as a serotonergic syndrome. Because of its different effects, the plant is widely used. An increase of clinical relevant risks should be considered in the add-on treatments.

This study is to investigate the effects of a Chinese prescription (FF), compatibility of Rhodiola crenulata, Cordyceps militaris and Rheum palmatum, on nephropathy in type 1 diabetic rats induced by streptozocin. According to fasting blood glucose level, diabetic rats were divided into three groups: model group, insulin-treated group and FF-treated group. Parameters for evaluating the glucose & lipid metabolism and the renal function were monitored dynamically. Levels of oxidative stress were detected ten weeks later. The results show that FF could significantly decrease the level of serum glucose and lipid profiles, improve the renal functions by decreasing blood urea nitrogen, urine albumin excretion and urease activity; FF could also affect on oxidative stress. In conclusion, Chinese prescription FF could ameliorate hyperglycemia-mediated renal damage in type 1 diabetic rats. These effects may be related to its regulation on the metabolism of glucose and lipid, the microcirculation disturbance and the oxidative stress.

The antidepressant-like activity of an extract of the roots of Rhodiola rosea (RR), its combination with piperine containing extract (RPE), pure substances isolated from Rhodiola, such as rhodioloside, rosavin, rosin, rosarin, tyrosol, cinnamic alcohol, cinnamaldehyde and cinnamic acid has been assessed in laboratory animals through application of the Porsolt behavioural despair assay. RR increased the swimming time of rats in a dose dependent manner (ED50=7 mg/kg) and, when administered at 20mg/kg, exhibited a stronger anti-depressant type effect than either imipramine (at 30 mg/kg) or an extract of Hypericum perforatum (at 20mg/kg). Rhodioloside, and tyrosol were identified as active principles of the extract, whereas rosavin, rosarin, rosin, cinnamic alcohol, cinnamaldehyde, cinnamic acid were inactive. A fixed combination of rhodioloside, rosavin, rosarin and rosin was more active than any of the individual components alone, indicating a synergistic effect of the ingredients in RR extract. Piperine in combination with Rhodiola (RPE) distorts pharmacological effect of Rhodiola most probably due to changes of pharmacokinetic profile of rhodioloside and rosavin. RPE cannot provide predictable therapeutic effect due to herb-herb interaction. Moreover, concomitant treatment of RPE with other drugs should also be excluded due to drug-piperine interaction.

11. Ann Agric Environ Med. 2026 Mar 25;33(1):3-11. doi: 10.26444/aaem/213417. Epub 2025 Dec 9. Clinical evidence for the adaptogenic effects of Withania somnifera and Rhodiola rosea - A systematic review with molecular interpretation of psychometric outcomes. Łuszczak J(1), Kocki J(2). Author

Adaptogens are synthetic compounds (bromantane, levamisole, aphobazole, bemethyl, etc.) or plant extracts that have the ability to enhance the body's stability against physical loads without increasing oxygen consumption. Extracts from Panax ginseng, Eleutherococcus senticosus, Rhaponticum carthamoides, Rhodiola rosea, and Schisandra chinensis are considered to be naturally occurring adaptogens and, in particular, plant adaptogens. The aim of this study is to evaluate the use of plant adaptogens in the past and now, as well as to outline the prospects of their future applications. The use of natural adaptogens by humans has a rich history-they are used in recovery from illness, physical weakness, memory impairment, and other conditions. About 50 years ago, plant adaptogens were first used in professional sports due to their high potential to increase the body's resistance to stress and to improve physical endurance. Although now many people take plant adaptogens, the clinical trials on human are limited. The data from the meta-analysis showed that plant adaptogens could provide a number of benefits in the treatment of chronic fatigue, cognitive impairment, and immune protection. In the future, there is great potential to register medicinal products that contain plant adaptogens for therapeutic purposes.

INTRODUCTION: The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity. OBJECTIVE: To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones. METHODS: A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020. RESULTS: Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation. CONCLUSION: For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required.