Rhodiola Rosea

BACKGROUND: Mild depression lacks a consistent definition across diagnostic criteria and rating scales, posing challenges to standardizing treatment strategies. International guidelines predominantly recommend psychotherapy as the first-line treatment for mild depression, while the use of antidepressants remains contentious. Supplements such as omega-3 fatty acids, St. John's Wort, and magnesium have garnered attention as alternative therapeutic options for depression. This systematic review aims to assess the efficacy of pharmacological interventions, including supplements, in the treatment of mild depression. METHODS: Comprehensive searches were performed in PubMed and Embase through November 2024 to identify randomized controlled trials (RCTs) investigating pharmacotherapy or supplements for mild depression diagnosed using standardized criteria. Eligible studies underwent screening and risk of bias assessment utilizing the ROB2 tool. Data on remission rates, symptom improvement, dropout rates, and adverse events were extracted, with meta-analyses conducted where applicable. RESULTS: Eight RCTs comprising 1049 participants met inclusion criteria. Among the agents studied, St. John's Wort was analyzed in two trials, both comparing it to fluoxetine. A meta-analysis found no significant difference in response rates between the two treatments (risk ratio [RR] = 0.96, 95% CI: 0.78-1.18) or dropout rates (RR = 1.08, 95% CI: 0.62-1.88). For other agents, single studies evaluated their effects. Eicosapentaenoic acid and Rhodiola rosea demonstrated significant improvements in depressive symptoms compared to placebo. In non-blinded trials, magnesium chloride showed efficacy in alleviating depressive symptoms. Other interventions, such as lavender, lemon balm, and transcranial electroacupuncture stimulation, were as effective as antidepressants. Conversely, S-adenosylmethionine did not produce significant improvements relative to placebo. CONCLUSION: This review demonstrates that certain supplements, such as eicosapentaenoic acids and Rhodiola rosea, are therapeutic options for mild depression. However, no RCTs compared antidepressants directly to placebo for mild depres

Objectives: To determine whether four weeks of Rhodiola rosea (RHO) supplementation improves intermittent exercise performance, post-exercise blood lactate concentrations, and decision-making under fatigue in competitive football players. Methods: Twenty-four male competitive football players completed a randomised, double-blind, placebo-controlled 4-week intervention (RHO vs. placebo). Outcomes included Yo-Yo IR2, repeated-sprint ability (RSA), post-RSA blood lactate (0, 3, 5 min), football-specific technical tests (passing and shooting), a video-based decision-making task (reaction time and accuracy), GPS-derived match running metrics, countermovement jump (CMJ), foot tapping (TAP), and haematological markers. Results: Yo-Yo IR2 performance significantly improved in the RHO group (p = 0.012) and was superior to the placebo group (p = 0.046). For RSA, mean sprint time improved significantly from pre- to post-intervention in the RHO group (p = 0.017), whereas no significant change was observed in the placebo group. Post-intervention, mean sprint time was significantly better in RHO than placebo (p = 0.041), with no between-group difference observed at baseline. Best sprint time showed no between-group difference (p = 0.723). Post-exercise blood lactate concentrations were significantly lower in RHO than placebo at 0, 3, and 5 min (all p < 0.05). Under fatigue, the RHO group demonstrated faster reaction time (p = 0.042) and higher decision accuracy (p = 0.049) than placebo. Additionally, the RHO group showed significant pre- to post-intervention improvements in passing and shooting performance (p < 0.05), with between-group differences observed only for short-pass performance. Match total and high-speed running distances were higher in RHO, accompanied by increases in haemoglobin and haematocrit (p < 0.05). Conclusions: Four weeks of Rhodiola rosea supplementation enhanced high-intensity intermittent performance and decision-making under fatigue, with findings suggesting improved performance maintenance rather than increased peak sprint capacity.

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 (RR) is marketed as an adaptogen; however, evidence for acute/short-term effects-and especially dose-response effects-in trained adults across performance and cognition is limited. Objective: Test whether RR improves resistance performance (strength, power) and executive function in resistance-trained adults using a randomized crossover with placebo and a capsule-free baseline. Methods: In a randomized, double-blind, crossover trial with four conditions-no-capsule control (CON), placebo (PL), low-dose RR (LDRR), and high-dose RR (HDRR). Twenty-seven resistance-trained adults completed the conditions. Day-7 testing included bench press (BP) and leg press (LP) 1-repetition maximum (1RM); a third set to failure at 60% 1RM with set-3 volume; Tendo mean/peak power; a 30 s Wingate; and the Stroop Color-Word Test. Secondary endpoints were Rating of Perceived Exertion (RPE), Readiness to perform using a Visual Analog Scale (VAS), and hemodynamics. Results: Versus CON, LDRR increased BP 1RM (+5.59 kg; p = 0.003), set-3 repetitions (+4.30; p < 0.001), set-3 volume (+168.6 kg; p < 0.001), and mean power (+29.7 W; p = 0.026). HDRR increased set-3 repetitions (+2.78; p = 0.005) and peak power (+34.2 W; p = 0.026), with a trend for set-3 volume (p = 0.086). LP 1RM exceeded CON with LDRR (+35.7 kg; p < 0.001) and HDRR (+47.7 kg; p < 0.001); contrasts vs. PL were significant. Wingate outcomes showed no consistent effects. Stroop improved vs. CON across all sections: Word +10.5 to +17.4 counts (p < 0.05), Color +6.1 to +12.0 (p ≤ 0.03), and Color-Word +10.2 to +18.9 (p < 0.001). Conclusions: Short-term RR consumption, regardless of dose or gender, improved resistance performance and significantly enhanced Stroop outcomes, with minimal changes in anaerobic cycling and RPE, and no consistent acute hemodynamic effects.

Objectives: This study aims to evaluate the effects of short-term Rhodiola rosea supplementation on simulated game performance, perceived fatigue, and aerobic capacity in basketball players. Methods: A total of 48 professional male basketball players participated in this study. The participants were randomly divided into a Rhodiola rosea group (RHO group, n = 24) and a Control group (CTR group, n = 24). During the experiment, the RHO group received continuous 28-day Rhodiola rosea supplementation, while the CTR group received empty capsules without being informed. Statistical analysis was performed using SPSS 22.0 software. A two-way mixed ANOVA (2 × 2) group (CTR/RHO) × time (Pre-test/Post-test) was conducted to compare differences. Results: In comparison to the CTR group, the RHO group showed significant differences in total completion time in the simulated game (p = 0.046), heart rate 60 s after the simulated game (p = 0.026), 5 km run (p = 0.027), YO-YO test (p = 0.036), VO2max (p = 0.034) and total antioxidant capacity (p = 0.044) compared to the CTR group. Within the RHO group, pre- and post-test comparisons revealed significant improvements in total completion time (p = 0.000), heart rate 30 s (p = 0.021) and 60 s (p = 0.016) after the simulated game, RPE score (p = 0.030), Countermovement jump test (p = 0.036), 5 km run (p = 0.000), YO-YO test (p = 0.000), VO2max (p = 0.000) and Superoxide Dismutase (p = 0.011). Conclusions: Short-term Rhodiola rosea supplementation can improve sprint performance and reduce perceived fatigue in basketball players during simulated games, enhance aerobic work capacity, and delay fatigue.

BACKGROUND: This study aimed to evaluate the synergistic effect of salidroside and pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) complicated by lower extremity deep vein thrombosis (LEDVT). METHODS: Eighty-two patients with COPD and LEDVT were randomly assigned to a control group (n = 41; low-molecular-weight heparin calcium plus pulmonary rehabilitation) or a combined group (n = 41; pulmonary rehabilitation plus salidroside). Clinical efficacy, hemorheological parameters, and serum hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) levels were compared. RESULTS: The total effective rate was higher in the combined group (95.12 %) than in the control group (75.61 %; P = 0.045), with no difference in adverse event incidence (17.07 % vs 9.76 %; P = 0.331). After 14 days, the combined group showed greater improvement in swelling, pain, skin temperature, and Homans's sign (all P < 0.05). Hemorheological parameters improved more significantly, including plasma viscosity (0.70 ± 0.08 vs 1.25 ± 0.30 mPa s), high-shear viscosity (4.10 ± 0.22 vs 5.00 ± 0.45 mPa s), and low-shear viscosity (7.84 ± 0.20 vs 10.93 ± 0.43 mPa s; all P < 0.001). HIF-1α levels were lower and VEGF levels higher in the combined group (both P < 0.001). CONCLUSION: Salidroside combined with pulmonary rehabilitation significantly improved clinical outcomes, oxygenation, and endothelial repair in COPD with LEDVT, likely via modulation of the HIF-1α/VEGF pathway, without increasing adverse effects.

PURPOSE: This study aimed to assess the impact of Rhodiola rosea (RR) supplementation on the dynamics of the accommodative response and digital eye strain (DES) symptoms following 30-min visual tasks with different levels of cognitive demand. METHODS: Eighteen young adults (mean age ± SD: 24.6 ± 4.0 years) participated in this placebo-controlled, triple-blind, balanced crossover study. Participants completed four sessions separated by 1 week in a randomised order. The sessions differed in the supplement (RR or placebo) and cognitive demand of the visual task (Stroop test or control video). The supplementation consisted of 1200 mg of RR or placebo per day for 4 days (two 300 mg capsules every 12 h) and a washout period of 3 days was allowed before the subsequent condition. The lag and variability of the accommodative response were measured at 500, 40 and 20 cm using an open-field autorefractor, and DES symptoms were assessed using a 10-item questionnaire. RESULTS: RR supplementation caused a reduction in the variability of accommodation (p = 0.007) and the perceived levels of 'Blurred vision when looking into the distance at the end of the near task' (p = 0.009). However, the lag of accommodation (p = 0.15) and the remainder of the DES symptoms were unaffected by the ingestion of RR (p > 0.05 in all cases). The reduction in the variability of accommodation after RR intake was observed at 40 and 20 cm (p-values <0.001 and 0.04, respectively), but not at far distance (500 cm, p = 0.40). CONCLUSIONS: These findings show that RR supplementation (1200 mg/day for 4 days) produced a reduction in the variability of accommodation and one of the assessed DES symptoms, suggesting that it could be considered as a potential strategy to prevent or manage DES. However, further research is needed to determine its clinical relevance and optimise dosage and timing. © 2025 The Author(s). Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

Objectives: This study aimed to explore the effects of four days of Rhodiola Rosea (RR) supplementation on bench-press and bench-pull exercises under resting or mental fatigue conditions in young healthy individuals. Methods: Eighteen participants (seven women) visited the laboratory on five occasions separated by 7 days-one preliminary session and four experimental sessions. In the preliminary session, participants were familiarised with the Stroop and Multiple Object Tracking tests, after which their one-repetition maximum loads for bench presses and bench pulls were determined. The four experimental sessions had the same protocol, differing only in the supplement (RR or placebo) and mental task conditions (Stroop test or control video). Participants were assigned randomly and counterbalanced to each experimental condition: (I) RR and Stroop test, (II) RR and control video, (III) placebo and Stroop test, and (IV) placebo and control video. Results: The main findings indicate that RR supplementation has trivial-to-small effects in terms of mental fatigue, visuo-cognitive processing, or perceived exertion. However, RR was significantly superior to placebo on strength performance in the control video condition during some sets, as it increased the number of repetitions performed in the bench press and the fastest velocity in the bench pull. Out of 52 comparisons, 17 small effect sizes were observed, with 14 favouring RR and 3 favouring placebo, with the remaining differences being trivial. Conclusions: These results suggest that short-term RR supplementation is safe and provides its main ergogenic effects on physical performance rather than in visuo-cognitive or mental outcomes.

BACKGROUND: This study investigated the effects of combined Rhodiola rosea (RHO) and caffeine (CAF) supplementation on lower limb explosive power and fatigue recovery in volleyball players, aiming to validate their potential synergistic effects. METHODS: A randomized, double-blind, placebo-controlled design was implemented involving 48 male volleyball athletes allocated into four groups: placebo (CTR), Rhodiola rosea (RHO), caffeine (CAF), and combined (RHO + CAF). Over four weeks, participants engaged in twice-weekly high-intensity lower limb resistance training, with performance evaluated through multiple tests, including two-step-approach jump height, countermovement jump (CMJ), five-jump test (5 JT), continuous 20 vertical jumps, and intermittent jump recovery alongside Rate of Perceived Exertion (RPE) assessments. RESULTS: Results showed that the combined supplementation (RHO + CAF) group exhibited significant improvement across multiple performance metrics. In particular, the combined group demonstrated the highest increases in jump height and the least power decline during high-frequency jumps, outperforming the CTR and other supplementation groups (p < 0.05). Additionally, RHO + CAF supplementation significantly lowered RPE scores, particularly in the final week of training, indicating improved perceived fatigue and recovery. CONCLUSIONS: This study suggests that combining RHO and CAF optimizes high-intensity performance by enhancing explosive power, reducing fatigue, and improving recovery, presenting an effective nutritional strategy for volleyball athletes.

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.

OBJECTIVES: Chewing gum has been shown to improve aspects of cognition and mood with sustained attention being particularly receptive to the effects of chewing. Chewing gum may also be a useful vehicle for administering functional ingredients. The herbal extract Rhodiola rosea and certain B-vitamins have previously been shown to improve aspects of cognition and subjective state, but their combined effects have not been studied to date. METHODS: The current randomised, placebo-controlled, double-blind, balanced crossover study compared the effects of a functional gum containing Rhodiola rosea and B-vitamins to flavour-matched regular chewing gum and a flavour-matched placebo. Thirty-six healthy young participants completed measures of attention and mood at baseline, during chewing, and 1-h after chewing. RESULTS: Chewing both functional and regular gum was shown to reduce errors on a digit vigilance task compared to placebo irrespective of whether measured during or after chewing. There were no benefits to adding functional ingredients to the gum. DISCUSSION: Future chewing research should consider different formats of placebo. Sex differences in response to chewing and the impact of rate and intensity of chewing should also be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05544500.

Comment in J Clin Anesth. 2024 Oct;97:111553. doi: 10.1016/j.jclinane.2024.111553. Comment on J Clin Anesth. 2024 Aug;95:111473. doi: 10.1016/j.jclinane.2024.111473.

Several studies utilizing Rhodiola rosea, which contains a complex mixture of phytochemicals, reported some positive drug-drug interaction (DDI) findings based on in vitro CYP450's enzyme inhibition, MAO-A and MAO-B inhibition, and preclinical pharmacokinetic studies in either rats or rabbits. However, variation in and multiplicity of constituents present in Rhodiola products is a cause for concern for accurately evaluating drug-drug interaction (DDI) risk. In this report, we examined the effects of bioengineered, nature-identical salidroside on the inhibition potential of salidroside on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 utilizing human liver microsomes, the induction potential of salidroside on CYP1A2, CYP2B6 and CYP3A4 in cryopreserved human hepatocytes, the inhibitory potential of salidroside against recombinant human MAO-A and MAO-B, and the OATP human uptake transport inhibitory potential of salidroside using transfected HEK293-OATP1B1 and OATP1B3 cells. The results demonstrate that the bioengineered salidroside at a concentration exceeding the predicted plasma concentrations of <2 µM (based on 60 mg PO) shows no risk for drug-drug interaction due to CYP450, MAO enzymes, or OATP drug transport proteins. Our current studies further support the safe use of salidroside in combination with other drugs cleared by CYP or MAO metabolism or OATP-mediated disposition.

Depression is considered the most important disorder affecting mental health. The aim of this systematic integrative review was: (i) to describe the effects of supplementation with adaptogens on variables related to depression in adults; and (ii) to discuss the potential combination with physical exercise to aid planning and commissioning future clinical research. An integrative review was developed complementing the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PROSPERO registration: CRD42021249682). A total of 41 articles met the inclusion criteria. With a Price index of 46.4%, we found that: (i) Hypericum perforatum (St. John's Wort) is the most studied and supported adaptogen (17/41 [41.46%], three systematic reviews with meta-analysis) followed by Crocus sativus L. or saffron (6/41 [14.63%], three systematic reviews with meta-analysis and two systematic reviews); (ii) it is possible that the significantly better performance of adaptogens over placebo is due to the reduction of allostatic load via the action of secondary metabolites on BDNF regulation; and, (iii) the number of studies reporting physical activity levels is limited or null for those that combine an exercise program with the consumption of adaptogens. Aware of the need for a multidisciplinary approach for depression treatment, this systematic integrative review provides an up-to-date view for supporting the use of St. John's Wort and saffron as non-pharmacological strategies while also help commissioning future research on the efficacy of other adaptogens. It also contributes to the design of future clinical research studies that evaluate the consumption of herbal extracts plus physical exercise, mainly resistance training, as a potentially safe and powerful strategy to treat depression.

Retraction in Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):548. doi: 10.1080/21691401.2023.2271702. Expression of concern in Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):1258. doi: 10.1080/21691401.2020.1827587. Salidroside is an active ingredient extracted from Rhodiola rosea that has anti-tumor activities. The current paper attempted to assess the impact of Salidroside on gastric cancer (GC) and explore the potential mechanism. GC cell lines (SNU-216 and MGC803) and gastric epithelial cell line GES-1 were treated with Salidroside. CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were respectively performed to evaluate GC cells phenotype. qRT-PCR and western blot were conducted to reveal the downstream genes and signaling of Salidroside. We found that 800 μM Salidroside was capable of reducing GC cells viability, while has no such impacts on GES-1 cells. Salidroside inhibited GC cells proliferation, migration, invasion and promoted apoptosis, which coupled with the down-regulation of p21, Bcl-2, MMP2, RhoA, p-ROCK1, Vimentin and the up-regulations of CyclinD1, Bax, cleaved caspases. miR-99a was found to be highly expressed in response to Salidroside treatment. Besides, the inhibition of MAPK/ERK and PI3K/AKT signaling induced by Salidroside was attenuated by miR-99a silence and in this process, IGF1R worked as a target of miR-99a. The anti-GC effect of Salidroside was also confirmed in a mouse model of GC. The promoting effect of Salidroside on miR-99a expression was also verified in vivo. Furthermore, Salidroside promoted the cisplatin-sensitivity of SGC7901/DDP cells. In conclusion, this study demonstrated that Salidroside possessed anti-GC effects through regulating miR-99a/IGF1R axis and inhibiting MAPK/ERK and PI3K/AKT pathways.

OBJECTIVES: Assessment of adverse drug interactions with herbal preparations (HP), i.e., plant medicines and nutritional supplements which contain plant extracts. METHODS: Analysis of 147 cases of adverse events with clinical picture indicating probability or certainty of resulting from inclusion of HP into the applied pharmacotherapy (mostly psychotropic drugs). RESULTS: The most common effect of interactions between SSRI or SNRI antidepressants and HP were hemorrhagic complications associated with Japanese ginkgo biloba (27.45% of complications in this subgroup). Another common complication was serotonin syndrome (SS) (11.8%) occurring during the use of ginseng (one case of SS after the addition of bacopa). In the group of antipsychotic drugs, the highest number of interactions was observed in the case of haloperidol, and the highest number of complications (29.8%) was associated with ginseng (including 6 cases of ventricular arrhythmias in combination with haloperidol), milk thistle (including 7 cases of pancreatitis in combination with haloperidol or risperidone, 1 case of hepatotoxicity after adding aripiprazole) and rhodiola rosea. As for hypnotics and sedatives - interactions with ginseng were most frequently reported, mainly intensified sedative effects, cognitive disorders and disturbances in consciousness. In 132 cases, withdrawal of the plant preparation resulted in a decrease in the severity of the reported adverse reactions or a complete resolution of the described symptoms. CONCLUSIONS: HP (especially ginseng, rhadiola rosea, ginkgo biloba, milk thistle) are associated with a significant risk of pharmacokinetic and pharmacodynamic interactions with psychotropic drugs. Because of the resulting complications and side effects, any decision to include a herbal supplement should be preceded by a detailed safety analysis with benefit and risk assessment.

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

31. Oncol Rep. 2017 Nov;38(5):3094-3102. doi: 10.3892/or.2017.5940. Epub 2017 Sep 6. 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 C(1), Cui J(1), Wu R(1), Jing J(1), Zhang S(1), Chen H(

PURPOSE: The aim of the present study was to evaluate the effect of the herbal drug Rhodiola rosea on the activity of the cytochrome P-450 (CYP) enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in humans. METHODS: In a randomized cross-over study, 13 healthy volunteers were given a cocktail with single doses of the CYP substrates caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4) with and without 14 days of pretreatment with a commercially available R. rosea product (Arctic Root, produced by the Swedish Herbal Institute). Four hours after intake of the drug cocktail, a blood sample was obtained, the serum concentrations of the drugs and their metabolites were analyzed, and the metabolic ratios were calculated as a measure of CYP enzyme activity. RESULTS: A statistically significant 21% decrease in the EXP-3174/losartan ratio was found after pretreatment with R. rosea (p = 0.023), indicating a reduced CYP2C9 metabolic activity. The effect was more pronounced in CYP2C9 extensive metabolizers than in CYP2C9 intermediate and poor metabolizers. For the other CYP enzymes tested, no significant effects were observed. CONCLUSIONS: This study indicates that R. rosea inhibits the metabolic capacity of CYP2C9 in humans. Although the effect is modest, it might be clinically relevant during treatment with CYP2C9 substrates with a narrow therapeutic index, such as phenytoin and warfarin.

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.

AIM: In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B12) and a mixture of vitamins B1+B6+B12 was investigated in the mouse formalin test. METHODS: Individual dose response curves of the Rhodiola rosea ethanol extract, as well as B-vitamins alone or in a mixture were evaluated in mice in which nociception was induced with 2% formalin intraplantarly. The antinociceptive mechanisms of the Rhodiola rosea were investigated by exploring the role of the opioid and serotonin receptors and the nitric oxide pathway. Isobolographic analysis was used to evaluate the pharmacological interactions between the Rhodiola rosea ethanol extract and each B-vitamin individually or the mixture of vitamins B1+B6+B12 by using the ED30 and a fixed 1:1 ratio combination. RESULTS: Administration of the Rhodiola rosea extract alone or in combination with all of the vitamins produced a significant and dose-dependent antinociceptive response. The antinociceptive effect of the Rhodiola rosea extract (ED50=81 mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT1A, GABA/BDZs and opioid receptors and by blocking mediators of the nitric oxide/cGMP/K(+) channels pathway. Isobolograms demonstrate that all of the combinations investigated in this study produced a synergistic interaction experimental ED30 values were significantly smaller than those calculated theoretically. CONCLUSIONS: These results provide evidence that a Rhodiola rosea ethanol extract in combination with B-vitamins produces a significant diminution in the nociceptive response in a synergistic manner, which is controlled by various mechanisms. These findings could aid in the design of clinical studies and suggest that these combinations could be applied for pain therapy.

CONTEXT: Despite the abundance of knowledge regarding high-altitude pulmonary edoema (HAPE) and high-altitude pulmonary hypertension (HAPH), their prevalence continues to be on the rise. Thus, there is an urgent need for newer safe, effective, and relatively economic drug candidates. China is particularly known for the use of medicinal plants. OBJECTIVE: This review summarizes the medicinal plants used for HAPE and HAPH in the past 30 years, as well as some potential plants. METHODS: Publications on HAPE and HAPH from 1990 to 2020 were identified using Web of Science, PubMed, SCOPUS, Springer Link, Google Scholar databases, Chinese Clinical Trial Registry and CNKI with the following keywords: 'medicinal plants,' 'hypoxia,' 'high altitude pulmonary edema,' 'high altitude pulmonary hypertension,' 'pathophysiology,' 'mechanisms,' 'prevention,' 'treatment,' 'human,' 'clinical,' 'safety,' and 'pharmacokinetics.' RESULTS: We found 26 species (from 20 families) out of 5000 plants which are used for HAPE and HAPH prevention or treatment. Rhodiola rosea Linn. (Crassulaceae) is the most widely utilized. The most involved family is Lamiaceae, which contains 5 species. DISCUSSION AND CONCLUSIONS: We mainly reviewed the medicinal plants and mechanisms for the treatment of HAPE and HAPH, and we also assessed related toxicology experiments, pharmacokinetics and bioavailability. Potential medicinal plants were also identified. Further research is needed to determine the pharmacological effects and active ingredients of these potential medicinal plants.

26. 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

The aim of this systematic review was to determine whether the supplementation with Rhodiola rosea (RR), an herb that has been used for centuries for its various properties, can have an effect on muscle damage and physical performance. The databases PubMed, Web of Science, and Cochrane Library were used to find studies published until March 2023. Randomized controlled trials, healthy participants, and no use of other supplements. The search strategy was conducted by two independent reviewers, and specific information was extracted from the selected studies. Thirteen studies were included with 263 participants (198 men and 65 women between 18 and 65 years old). Two studies followed acute supplementation, 5 chronic, and 6 combined both. The results were heterogenous, having 11 studies with some positive effects, while 2 studies show no effect in variables such as rating of perceive exertion, heart rate, antioxidant capacity, blood lactate, creatine kinase, or C-reactive protein. Two limitations were found, firstly, the difference between supplementation and exercise protocols, and secondly, the existence of unclear or high risk of bias in most of the studies included. Acute supplementation with RR has a positive effect on endurance performance and rating of perceived exertion (RPE). Chronic supplementation has a positive effect on anaerobic exercise performance, but not endurance exercise performance. Chronic supplementation may positively impact muscle damage during exercise. However, more high-quality studies are needed to firmly establish the clinical efficacy of RR. © 2023 John Wiley & Sons, Ltd.

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.

Background: Dietary supplements promoted for brain health and enhanced cognitive performance are widely available. Claims made for these products are directed not only to the elderly wishing to prevent or mitigate cognitive decline, but also young healthy populations looking to boost their cognitive performance. It is unclear whether these claims made on product bottles and through advertising match the science. Objectives: To explore the evidence on the efficacy and safety of single dietary supplement ingredients frequently marketed with claims of enhanced cognitive performance among healthy adults. Design: A systematic review. Results: Nine of 54 dietary supplement ingredients identified through a scoping review met the eligibility criteria with at least 3 published studies identified per ingredient, yielding 69 unique publications. Ingredients evaluated included Bacopa monnieri, choline, creatine, omega-3 fatty acids, Ginkgo biloba, ginseng, Rhodiola rosea, tyrosine, and valerian root, all in supplement form and compared with a placebo, at various serving sizes and durations of use. Conclusions: The low level of certainty in the state of the science, coupled with not always knowing what is in a dietary supplement product, make weighing risks and benefits difficult; these data hinder the ability to develop recommendations about using such ingredients for consumers interested in boosting their cognitive performance. Whereas certain trends regarding promising serving sizes or duration for use, are pointed to in this synthesis, when combined, studies are inconsistent and imprecise, and many are methodologically flawed. Potential solutions to address research gaps are offered, for future research next steps, which is needed to strengthen the evidence and inform decisions.

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.

BACKGROUND: Rhodiola rosea (R. rosea) is grown at high altitudes and northern latitudes. Due to its purported adaptogenic properties, it has been studied for its performance-enhancing capabilities in healthy populations and its therapeutic properties in a number of clinical populations. To systematically review evidence of efficacy and safety of R. rosea for physical and mental fatigue. METHODS: Six electronic databases were searched to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs), evaluating efficacy and safety of R. rosea for physical and mental fatigue. Two reviewers independently screened the identified literature, extracted data and assessed risk of bias for included studies. RESULTS: Of 206 articles identified in the search, 11 met inclusion criteria for this review. Ten were described as RCTs and one as a CCT. Two of six trials examining physical fatigue in healthy populations report R. rosea to be effective as did three of five RCTs evaluating R. rosea for mental fatigue. All of the included studies exhibit either a high risk of bias or have reporting flaws that hinder assessment of their true validity (unclear risk of bias). CONCLUSION: Research regarding R. rosea efficacy is contradictory. While some evidence suggests that the herb may be helpful for enhancing physical performance and alleviating mental fatigue, methodological flaws limit accurate assessment of efficacy. A rigorously-designed well reported RCT that minimizes bias is needed to determine true efficacy of R. rosea for fatigue.

Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen's d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies "herbomics", are areas of potential future research.

OBJECTIVE: To critically assess the current evidence from randomized clinical trials (RCTs) for or against the effectiveness or efficacy of Rhodiola rosea. DATA SOURCES: Systematic literature searches were performed in six electronic databases: AMED (1985-July 2009), CINAHL (1982-July 2009), The Cochrane Library (search in July 2009), EMBASE (1974-July 2009), MEDLINE (1950-July 2009) and Web of Science (searched in July 2009). No language restrictions were imposed. Reference lists of all retrieved articles were searched, and experts and manufacturers were contacted for unpublished RCT. REVIEW METHODS: RCTs testing the efficacy or effectiveness of mono-preparations of R. rosea as sole treatment administered orally against a control intervention in any human individual suffering from any condition or healthy human volunteers were included. Studies were selected, data extracted, and quality assessed by two independent reviewers. RESULTS: Eleven RCTs met the inclusion criteria; all were placebo-controlled. Six trials investigated the effects of R. rosea on physical performance, four on mental performance, and two in patients diagnosed with mental health condition. The methodological quality of most trials was moderate or good. Only few mild adverse events were reported. CONCLUSION: R. rosea may have beneficial effects on physical performance, mental performance, and certain mental health conditions. There is, however, a lack of independent replications of the single different studies. Five of the 10 RCTs reached more than three points on the Jadad score (i.e., good quality). More research seems warranted.