Characterization of the Anxiolytic Activity of Nunavik Rhodiola rosea

Abstract Rhodiola rosea is a medicinal plant used by the indigenous Inuit people of Nunavik and Nunatsiavut, Eastern Canada, as a mental and physical rejuvenating agent. This traditional use led to the present investigation of R. rosea in the context of anxiety disorders. An alcohol extract of R. rosea roots was characterized phytochemically and orally administered for three consecutive days to Sprague-Dawley rats at 8 mg/kg, 25 mg/kg, and 75 mg/kg body weight. The rats were subjected to three behavioral paradigms of anxiety, including the elevated plus maze, social interaction, and contextual conditioned emotional response tests. Rhodiola rosea showed dose-dependent anxiolytic activity in the elevated plus maze and conditioned emotional response tests, with moderate effects in the higher-anxiety SI test. The active dose varied according to the anxiety test. In order to elucidate a mechanism, the extract was further tested in an in vitro GABAA-benzodiazepine receptor-binding assay, where it demonstrated low activity. This study provides the first comparative assessment of the anxiolytic activity of Nunavik R. rosea in several behaviour models and suggests that anxiolytic effects may be primarily mediated via pathways other than the GABAA-benzodiazepine site of the GABAA receptor.

[1]  A. Caputi,et al.  Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats. , 2012, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[2]  F. Occhiuto,et al.  Rhodiola rosea Extract Protects Human Cortical Neurons against Glutamate and Hydrogen Peroxide‐induced Cell Death Through Reduction in the Accumulation of Intracellular Calcium , 2012, Phytotherapy research : PTR.

[3]  M. Déciga-Campos,et al.  Neuropharmacological and Toxicity Evaluations of Ethanol Extract from Rhodiola Rosea , 2012 .

[4]  M. Trincavelli,et al.  The GABAA-BZR complex as target for the development of anxiolytic drugs. , 2012, Current topics in medicinal chemistry.

[5]  V. Trudeau,et al.  Anxiolytic activity of a supercritical carbon dioxide extract of Souroubea sympetala (Marcgraviaceae) , 2010, Phytotherapy research : PTR.

[6]  Michael Davis,et al.  Pharmacological treatments that facilitate extinction of fear: Relevance to psychotherapy , 2011, NeuroRX.

[7]  M. Todorova,et al.  Chemical composition of the essential oils of Rhodiola rosea L. of three different origins , 2010, Pharmacognosy magazine.

[8]  G. Ecker,et al.  Valerenic acid derivatives as novel subunit‐selective GABAA receptor ligands –in vitro and in vivo characterization , 2010, British journal of pharmacology.

[9]  Murray B Stein,et al.  The pharmacologic treatment of anxiety disorders: a review of progress. , 2010, The Journal of clinical psychiatry.

[10]  J. Sarris,et al.  Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. , 2010, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[11]  V. Trudeau,et al.  Ethnopharmacology of Q'eqchi' Maya antiepileptic and anxiolytic plants: effects on the GABAergic system. , 2009, Journal of ethnopharmacology.

[12]  R. Wong,et al.  The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats. , 2009, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[13]  Z. Ali,et al.  RP-HPLC determination of phenylalkanoids and monoterpenoids in Rhodiola rosea and identification by LC-ESI-TOF. , 2009, Biomedical chromatography : BMC.

[14]  Yuan-Shan Zeng,et al.  Pretreatment with Rhodiola rosea extract reduces cognitive impairment induced by intracerebroventricular streptozotocin in rats: implication of anti-oxidative and neuroprotective effects. , 2009, Biomedical and environmental sciences : BES.

[15]  O. Grundmann,et al.  Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice. , 2009, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[16]  Andrew Marston,et al.  Monoamine oxidase inhibition by Rhodiola rosea L. roots. , 2009, Journal of ethnopharmacology.

[17]  E. Olsson,et al.  A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Standardised Extract SHR-5 of the Roots of Rhodiola rosea in the Treatment of Subjects with Stress-Related Fatigue , 2008, Planta medica.

[18]  J. Arnason,et al.  Phytochemical Analysis of Nunavik Rhodiola rosea L , 2008 .

[19]  Jamie D. Feusner,et al.  A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD). , 2008, Journal of alternative and complementary medicine.

[20]  J. Laugharne,et al.  Complementary and alternative medicine in the treatment of anxiety and depression , 2008, Current opinion in psychiatry.

[21]  J. Arnason,et al.  Ethnopharmacological investigation of plants used to treat susto, a folk illness. , 2007, Journal of ethnopharmacology.

[22]  L. Mattioli,et al.  Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice , 2007, Phytotherapy research : PTR.

[23]  M. Récasens,et al.  Anxiolytic properties of green tea polyphenol (−)-epigallocatechin gallate (EGCG) , 2006, Brain Research.

[24]  Y. Kiso,et al.  Effects of Beer and Hop on Ionotropic γ-Aminobutyric Acid Receptors , 2006 .

[25]  H. Xue,et al.  Neuroactive flavonoids interacting with GABAA receptor complex. , 2005, Current drug targets. CNS and neurological disorders.

[26]  Olga V. Demler,et al.  Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. , 2005, Archives of general psychiatry.

[27]  J. Atack.  The benzodiazepine binding site of GABAA receptors as a target for the development of novel anxiolytics , 2005, Expert opinion on investigational drugs.

[28]  M. Zarrindast,et al.  Cholecystokinin and GABA interaction in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety , 2005, Physiology & Behavior.

[29]  H. Xue,et al.  Development of effective therapeutics targeting the GABAA receptor: naturally occurring alternatives. , 2004, Current pharmaceutical design.

[30]  G. Zapesochnaya,et al.  Chemical composition of the rhizomes of the Rhodiola rosea by the HPLC method , 1991, Chemistry of Natural Compounds.

[31]  S. File,et al.  A review of 25 years of the social interaction test. , 2003, European journal of pharmacology.

[32]  R. Kessler,et al.  The use of complementary and alternative therapies to treat anxiety and depression in the United States. , 2001, The American journal of psychiatry.

[33]  D. Treit,et al.  Effects of centrally administered anxiolytic compounds in animal models of anxiety , 1999, Neuroscience & Biobehavioral Reviews.

[34]  S. File,et al.  Stimulation of benzodiazepine receptors in the dorsal hippocampus and median raphé reveals differential GABAergic control in two animal tests of anxiety , 1998, The European journal of neuroscience.

[35]  Janet E. Jackson,et al.  Behavioural Effects in Mice of Subchronic Buspirone, Ondansetron and Tianeptine. II. The Elevated Plus-Maze , 1997, Pharmacology Biochemistry and Behavior.

[36]  S. File,et al.  5-HT1A and benzodiazepine receptors in the basolateral amygdala modulate anxiety in the social interaction test, but not in the elevated plus-maze , 1996, Brain Research.

[37]  F. Graeff,et al.  Ethopharmacological analysis of rat behavior on the elevated plus-maze , 1994, Pharmacology Biochemistry and Behavior.

[38]  R. Rodgers,et al.  Antianxiety and behavioral suppressant actions of the novel 5-HT1A receptor agonist, flesinoxan , 1994, Pharmacology Biochemistry and Behavior.

[39]  S. File.  USEFULNESS OF ANIMAL MODELS WITH NEWER ANXIOLYTICS , 1992, Clinical neuropharmacology.

[40]  S. File,et al.  Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat , 1985, Journal of Neuroscience Methods.

[41]  F. Segal,et al.  A CHARACTERIZATION OF FIBRANT SEGAL CATEGORIES , 2006, math/0603400.