HighlightsRhodiola roseais a plant containing biologicallyactive substances[1] which is used in traditionalmedicine[2].Potential forR. roseato be used as preventativeor alternative treatment for mild mood and stressdisorders[3].Some studies indicate the mode of action ofR. roseamay be due to cell response regulation at the tran-scriptional level[1, 4].BackgroundRhodiola rosea, commonly known as Golden Root, isof theRhodiolagenus which was traditionally usedfor medicines in Asia[2]. The roots contain biologi-cally active substances including flavonoids and phe-nolic glycosides[1] and have been used in traditionalmedicine for its adaptogenic, antidepressant, and anti-inflammatory effects[2]. Historical and traditional use, aswell as early limited animal clinical trials, indicate thatthere is an encouraging potential for the use ofRhodiolaroseain fatigue, cognition, and mood homeostasis[5].Mode of ActionR. roseahas several suggested mechanisms of action,none of which so far have undergone significant testingto confirm efficacy.Figure 1:Rhodiola roseaplant.In some animal studies, changes to cortisol secretionwere found – however other studies have not corroboratedthis and similar studies have actually shown no changesin cortisol secretion related toR. roseaintake[1].However, it has been proposed that the mode of actionofR. roseacould be through cell response regulation atthe transcriptional level[1]. That particular study con-cluded by stating that although the exact mechanism inwhichR. roseaacts is unknown and requires further in-vestigation, that some parameters of psycho-motor per-formance were seen in young, healthy, and physically ac-tive men[1].Data from both human and animal studies has sug-gested thatR. roseaappears to have a positive im-pact on hypothalamic-pituitary-adrenocortical (HPA)axis activity[6], an action which impacts the immune-response system.R. roseais also believed to increaseblood brain barrier permeability to dopamine and sero-tonin precursors[6].Lastly, an in-depth look at the effects of theR. roseaextracts and RNA expression data concluded thatRhodi-olahas a multi-targeted effect at the transcriptional levelon cell response regulation by affecting various signalingpathways and molecular networks which are associatedwith beneficial effects on emotional (aggressive) behav-ior, as well as psychological, neurological, cardiovascular,metabolic, endocrine, and gastrointestinal disorders[4].Pharmacological EffectsIt has been suggested through a variety of animal andhuman trials that chronic ingestion ofR. roseais un-likely to increase physical performance through opioidreceptor stimulus and antioxidant properties[1], whichare largely related to blood brain barrier permeability todopamine and serotonin precursors[6]. Although therehas not been any randomized, double-blind, placebo-controlled trials in humans forR. rosea, there are earlierclinical studies showing some indication thatR. roseacould be promising for treatment of Major DepressiveDisorder (MDD)[6].It was seen in one study of human nueroglia cell linesthat the biological activity ofR. roseaextracts actuallydiffered from the extracted purified compounds, and thusit cannot be excluded that there could be minor plantcomponents within theR. roseaextract that may affectbrain function[4]. Lastly, despite no influence ofR. roseasupplementation on oxidative stress parameters in a par-ticular study, it could not be excluded that some pheno-lic compounds ofR. roseaextract could be attributedto mental performance parameter improvements giventhe well-documented potential of flavonoids in promot-ing memory, learning, and cognitive function[1].Additionally, a 12-week study with aR. roseaex-tract in 50 individuals showed improvements in atten-tion network tasks (ANT), Go/No-go tasks, and dividedattention tasks[7]. Although longer treatment times anddouble-blind placebo studies are required, this early clin-ical study suggests a beneficial effect ofR. roseaon com-plex attention functions[7], an effect which was previ-ously mentioned in other studies examiningR. rosea’smode of action[1].Moreover,R. rosea’s adaptogenic properties previ-ously mentioned[2] were further examined. A litera-ture review concluded thatR. roseaextracts have thepotential to close the treatment gap for clinically rel-evant stress symptoms due to its dual mode of action(physical and psychological symptom relief), normaliza-tion of stress hormones, and increasing overall energy[3].It is important to note that this literature review doesnot recommendR. roseaextracts for serious secondarydiseases such as depression, anxiety, and hypertension,but rather that the extract be used as a preventativetreatment and first-line medical treatment for persis-tent stress and exhaustion, especially in conjunctionwith behavioral therapy or other non-pharmacologicaltreatments[3].Potential UsesGivenR. rosea’s lack of double-blind, placebo-controlled,randomized studies, its potential uses are fairly limitedin a strict medical setting. However, its usage in tradi-tional medicine[2], along with a favorable safety profileby the Committee on Herbal Medicinal Products (Eu-ropean Medicines Agency)[3, 8], and early clinical trialindications[1, 3, 4, 7, 6], indicate that there is potentialforR. roseato be used as a preventative or alternativetreatment for mild mood and stress disorders.Additionally, clinical trials in animals and cell linesindicate thatR. roseaand its extracts (albeit less effec-tive due to the loss of minor plant compounds) couldpotentially relieve some of the oxidative stresses[2, 4, 6]present in cellular reactions – making the use ofR. roseaas an adaptogen attractive.Lastly, according to literature reviews of traditionalmedicine practices,R. roseahas been historically usedfor anti-inflammatory purposes[2], which is supported bymore current research showing that the roots and plantcontains biologically active flavonoids and glycosides[1],among many other naturally occurring plant secondarymetabolites.References] E. Jówko, J. Sadowski, B. Długołęcka, D. Gierczuk,B. Opaszowski, and I. Cieśliński. Effects of rhodi-ola rosea supplementation on mental performance,physical capacity, and oxidative stress biomarkers inhealthy men.Journal of Sport and Health Science,7(4):473–480, 2018.[2] H. Chiang, H. Chen, C. Wu, P. Wu, and K. Wen.Rhodiola plants: Chemistry and biological activity.Journal of Food and Drug Analysis, 23(3):359–369,2015.[3] I. Anghelescu, D. Edwards, E. Seifritz, andS. Kasper. Stress management and the role of rhodi-ola rosea: a review.International Journal of Psychia-try in Clinical Practice, 22(4):242–252, 2018. PMID:29325481.[4] A. Panossian, R. Hamm, G. Wikman, and T. Efferth.Mechanism of action of rhodiola, salidroside, tyrosoland triandrin in isolated neuroglial cells: An interac-tive pathway analysis of the downstream effects usingrna microarray data.Phytomedicine, 21(11):1325–1348, 2014.[5] A. Panossian, G. Wikman, and J. Sarris. Rosen-root (rhodiola rosea): Traditional use, chemical com-position, pharmacology and clinical efficacy.Phy-tomedicine, 17(7):481–493, 2010.[6] J. Mao, Q. Li, I. Soeller, S. Xie, and J. Amsterdam.Rhodiola rosea therapy for major depressive disor-der: a study protocol for a randomized, double-blind,placebo- controlled trial.J Clin Trials, 4:170, 2014.[7] T. Koop, A. Dienel, M. Heldmann, and T. Münte.Effects of a rhodiola rosea extract on mental resourceallocation and attention: An event-related potentialdual task study.Phytotherapy Research, 34(12):3287–3297, 2020.[8] EMA and HMPC. Assessment report on rhodiolarosea l., rhizoma et radix. Technical report.This document was created on July 1, 2021 and last updatedon July 12, 2021.
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