Phytochemistry Reviews

, Volume 15, Issue 4, pp 515–536 | Cite as

Rhodiola rosea L.: from golden root to green cell factories

  • Andrey S. Marchev
  • Albena T. Dinkova-Kostova
  • Zsuzsanna György
  • Iman Mirmazloum
  • Ina Y. Aneva
  • Milen I. Georgiev


Rhodiola rosea L. is a worldwide popular plant with adaptogenic activities that have been and currently are exploited in the traditional medicine of many countries, as well as, examined in a number of clinical trials. More than 140 chemical structures have been identified which belong to several natural product classes, including phenylpropanoid glycosides, phenylethanoids, flavonoids and essential oils, and are mainly stored in the rhizomes and the roots of the plant. A number of mechanisms contribute to the adaptogenic activities of R. rosea preparations and its phytochemical constituents. Among them, the intrinsic inducible mammalian stress responses and their effector proteins, such as heat shock protein 70 (Hsp70), are the most prominent. Due to its popular medicinal use, which has led to depletion of its natural habitats, R. rosea is now considered as endangered in most parts of the world. Conservation, cultivation and micropropagation are all implemented as potential preservation strategies. A number of in vitro systems of R. rosea are being developed as sources of pharmaceutically valuable secondary metabolites. These are greatly facilitated by advances in elucidation of the biosynthetic pathways and the enzymes, which catalyse the production of these secondary metabolites in the plant. In addition, biotechnological approaches show promise towards achieving sustainable production of R. rosea secondary metabolites.


Roseroot Medicinal use Clinical trials In vitro systems Secondary metabolites 



2.4-Dichlorophenoxyacetic acid


Adverse events




Bcl-2-associated X protein


B-cell lymphoma-2


Cinnamyl alcohol


Cyclic adenosine monophosphate


Dry weight


Endothelial nitric oxide synthase


Gibberellic acid


Gas chromatography–mass spectroscopy


Good manufacturing practices


Hypoxia-inducible factors 1


High performance liquid chromatography


Heat shock protein 70


Indole-3-acetic acid


Indole-3-butyric acid




Methyl jasmonate


Murashige and Skoog


Naphtaleneacetic acid


Nuclear magnetic resonance


NAD(P)H:quinone oxidoreductase 1




Traditional herbal medicinal products




Tyrosine decarboxylase


UDP-glucose:tyrosol glucosyltransferase




Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.


  1. Abidov M, Grachev S, Seifulla R et al (2004) Extract of Rhodiola rosea radix reduces the level of C-reactive protein and creatinine kinase in the blood. Bull Exp Biol Med 138:63–64PubMedGoogle Scholar
  2. Akerfelt M, Morimoto R, Sistonen L (2010) Heat shock factors: integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol 11:545–555PubMedPubMedCentralCrossRefGoogle Scholar
  3. Akgul Y, Ferreira D, Abourashed E et al (2004) Lotaustralin from Rhodiola rosea roots. Fitoterapia 75:612–614PubMedCrossRefGoogle Scholar
  4. Asea A, Kaur P, Panossian A et al (2013) Evaluation of molecular chaperons Hsp72 and neuropeptide Y as characteristic markers of adaptogenic activity of plant extracts. Phytomedicine 20(14):1323–1329PubMedCrossRefGoogle Scholar
  5. Aslanyan G, Amroyan E, Gabrielyan E et al (2010) Double-blind, placebo-controlled, randomised study of single dose effects of ADAPT-232 on cognitive functions. Phytomedicine 17:494–499PubMedCrossRefGoogle Scholar
  6. Avula B, Wang Y, Ali Z et al (2009) RP-HPLC determination of phenylalkanoids and monoterpenoids in Rhodiola rosea and identification by LC-ESI-TOF. Biomed Chromatogr 23(8):865–872PubMedCrossRefGoogle Scholar
  7. Bai Y, Bi H, Zhuang Y et al (2014) Production of salidroside in metabolically engineered Escherichia coli. Sci Rep. doi: 10.1038/srep06640 Google Scholar
  8. Booker A, Jalil B, Frommenwiler D et al (2015) The authenticity and quality of Rhodiola rosea products. Phytomedicine. doi: 10.1016/j.phymed.2015.10.006 PubMedGoogle Scholar
  9. Brown R, Gerbarg P, Ramazanov Z (2002) Rhodiola rosea: a Phytomedicinal overview. HerbalGram 56:40–52Google Scholar
  10. Buchwald W, Mordalski R, Kuchrski W et al (2015) Effect of fertilization on roseroot (Rhodiola rosea L.) yield and content of active compounds. Acta Sci Pol Hortorum Cultus 14(2):109–121Google Scholar
  11. Buckley J, Lewis S (2009) The effects of an acute dose of Rhodiola rosea on exercise performance and cognitive function. J Int Soc Sports Nutr 6(1):P14PubMedCentralCrossRefGoogle Scholar
  12. Cai L, Wang H, Li Q (2008) Salidroside inhibits H2O2-induced apoptosis in PC12 cells by preventing cytochrome c release and inactivating of caspase cascade. Acta Biochim Biophys Sin 40(9):796–802PubMedCrossRefGoogle Scholar
  13. Chen X, Liu J, Gu X et al (2008) Salidroside attenuates glutamate-induced apoptotic cell death in primary cultured hippocampal neurons of rats. Brain Res 1238:189–198PubMedCrossRefGoogle Scholar
  14. Chen X, Zhang Q, Cheng Q et al (2009) Protective effect of salidroside against H2O2-induced cell apoptosis in primary culture of rat hippocampal neurons. Mol Cell Biochem 332(1–2):85–93PubMedCrossRefGoogle Scholar
  15. Chiang H, Chen H, Wu C (2015) Rhodiola plants: chemistry and biological activity. J Food Drug Anal 23:359–369CrossRefGoogle Scholar
  16. Committee on Herbal Medicinal Products (2012a) Community herbal monograph on Rhodiola rosea L., rhizoma et radix. EMA/HMPC/232091/2011Google Scholar
  17. Committee on Herbal Medicinal Products (2012b) Assessment report on Rhodiola rosea L., rhizoma et radix. EMA/HMPC/232100/2011Google Scholar
  18. Cuerrier A, Archambault M, Rapinski M et al (2015) Taxonomy of Rhodiola rosea L., with special attention to molecular analyses of Nunavik (Québec) populations. In: Cuerrier A, Ampong-Nyarko K (eds) Rhodiola rosea. Traditional herbal medicines for modern times. CRC Press, Taylor & Francis Group, pp 1–34Google Scholar
  19. Dayalan N, Kostov R, Dinkova-Kostova A (2015) Transcription factors Hsf1 and Nrf2 engage in crosstalk for cytoprotection. Trends Pharmacol Sci 36(1):6–14CrossRefGoogle Scholar
  20. Didukh YP (ed) (2009) Red Data Book of Ukraine: Flora. Ukrainian Scientific Publishers, Kyiv, p 900Google Scholar
  21. Dneprovskii I, Kim E, Iumanova T (1975) Seasonal development and growth of Rhodiola rosea L. in relation to introduction [as drug plant]. Biull Gl Bot Sada 98:27–34Google Scholar
  22. Dubichev A, Kurkin V, Zapesochnaya G et al (1991) Chemical composition of the rhizomes of the Rhodiola rosea by the HPLC method. Chem Nat Compd 27(2):161–164CrossRefGoogle Scholar
  23. Engler A, Melchior H (1964) Syllabus der Pflanzenfamilien. Gerbuder Borntraeger, BerlinGoogle Scholar
  24. Evstatieva L, Todorova M, Antonova D (2010) Chemical composition of the essential oils of Rhodiola rosea L. of three different origins. Pharmacogn Mag 6(24):256–258PubMedPubMedCentralCrossRefGoogle Scholar
  25. Fu K, Ohba H (2001) Rhodiola (Crassulaceae). In: Wu Z, Raven P (eds) Flora of China, vol 8. Science Press, Beijing, pp 251–268Google Scholar
  26. Furmanowa M, Oledzka H, Michalska M et al (1995) Rhodiola rosea L. (Roseroot): in vitro regeneration and the biological activity of roots. In: Bajaj YPS (ed) Biotechnology in agriculture and forestry, vol 33. Medicinal and Aromatic Plants VIII. Springer, Berlin, pp 412–426Google Scholar
  27. Furmanowa M, Skopińska-Rozewska E, Rogala E et al (1998) Rhodiola rosea in vitro culture-phytochemical analysis and antioxidant action. Acta Soc Bot Pol 67(1):69–73CrossRefGoogle Scholar
  28. Furmanowa M, Hartwich M, Alfermann A et al (1999) Rosavin as a product of glycosylation by Rhodiola rosea (roseroot) cell cultures. Plant Cell Tiss Org 56:105–110CrossRefGoogle Scholar
  29. Galambosi B (2006) Demand and availability of Rhodiola rosea L. raw material. In: Bogers R, Cracker L, Lange D (eds) Medicinal and aromatic plants. Springer, The Hague, pp 223–236CrossRefGoogle Scholar
  30. Galambosi B (2015) Cultivation of Rhodiola rosea in Europe. In: Cuerrier A, Ampong-Nyarko K (eds) Rhodiola rosea. Traditional herbal medicines for modern times. CRC Press, Taylor & Francis Group, pp 87–124Google Scholar
  31. Georgiev M, Agostini E, Ludwig-Müller J et al (2012) Genetically transformed roots: from plant disease to biotechnological resource. Trends Biotechnol 30(10):528–537PubMedCrossRefGoogle Scholar
  32. Ghiorghită G, Hârtan M, Maftei D et al (2011) Some considerations regarding the in vitro culture of Rhodiola rosea L. Rom Biotechnol Lett 16(1):5902–5908Google Scholar
  33. Grech-Baran M, Sykłowska-Baranek K, Giebułtowicz J et al (2013) Tyrosol glucosultransferase activity and salidroside production in natural and transformed root cultures of Rhodiola kirilowii (Regel) Regel et Maximowicz. Acta Biol Cracov Ser Bot 55(2):126–133Google Scholar
  34. Grech-Baran M, Sykłowska-Baranek K, Krajewska-Patan A et al (2014) Biotransformation of cinnamyl alcohol to rosavins by non-transformed wild type and hairy root cultures of Rhodiola kirilowii. Biotechnol Lett 36:649–656PubMedCrossRefGoogle Scholar
  35. Grech-Baran M, Sykłowska-Baranek K, Pietrosiuk A (2015) Biotechnological approaches to enhance salidroside, rosin and its derivatives production in selected Rhodiola spp. in vitro cultures. Phytochem Rev 14:657–674PubMedCrossRefGoogle Scholar
  36. Gryszczyńska A, Krajewska-Patan A, Dreger M et al (2012) Proanthocyanidins in Rhodiola kirilowii and Rhodiola rosea callus tissues and transformed roots-determination with UPLC–MS/MS method. Herba Pol 58(4):52–61Google Scholar
  37. Guan S, Feng H, Song B et al (2011a) Salidroside attenuates LPS-induced pro-inflammatory cytokine responses and improves survival in murine endotoxemia. Int Immunopharmacol 11(12):2194–2199PubMedCrossRefGoogle Scholar
  38. Guan S, Wang W, Lu J (2011b) Salidroside attenuates hydrogen peroxide-induced cell damage through a cAMP-dependent pathway. Molecules 16(4):3371–3379PubMedCrossRefGoogle Scholar
  39. György Z (2006) Glucoside production by in vitro Rhodiola rosea cultures. Dissertation, Acta Universitatis Ouluensis C Technica 244. Oulu University Press, OuluGoogle Scholar
  40. György Z, Hohtola A (2009) Production of cinnamyl glycosides in compact callus aggregate cultures of Rhodiola rosea through biotransformation of cinnamyl alcohol. In: Jain SM, Saxena P (eds) Protocols for in vitro cultures and secondary metabolite analysis of aromatic and medicinal plants. Methods in Molecular Biology, vol 547. Humana Press, New York, pp 305–312Google Scholar
  41. György Z, Tolonen A, Pakonen M et al (2004) Enhancement of the production of cinnamyl glycosides in CCA cultures of Rhodiola rosea through biotransformation of cinnamyl alcohol. Plant Sci 166(1):229–236CrossRefGoogle Scholar
  42. György Z, Tolonen A, Neubauer P et al (2005) Enhanced biotransformation capacity of Rhodiola rosea callus cultures for glycosid production. Plant Cell Tiss Org Cult 83:129–135CrossRefGoogle Scholar
  43. György Z, Jaakola L, Neubauer P et al (2009) Isolation and genotype-dependent, organ-specific expression analysis of a Rhodiola rosea cDNA encoding tyrosinedecarboxylase. J Plant Physiol 166:1581–1586PubMedCrossRefGoogle Scholar
  44. Hauser G, Dayao E, Wasserloos K (1996) HSP induction inhibits iNOS mRNA expression and attenuates hypotension in endotoxin-challenged rats. Am J Physiol 271(6 Pt 2):H2529–H2535PubMedGoogle Scholar
  45. Hegi G (ed) (1963) Rhodiola, Rosenwurz. In: Illustrierte Flora von Mitteleuropa. Zweite völlig neubearbeitete Auflage. Band IV/2, Lieferung 2/3. Paul Parey, Hamburg, Berlin, pp 99–102Google Scholar
  46. Hernández-Santana A, Pérez-López V, Zubeldia J (2014) A Rhodiola rosea root extract protects skeletal muscle cells against chemically induced oxidative stress by modulating heat shock protein 70 (HSP70) expression. Phytother Res 28(4):623–628PubMedCrossRefGoogle Scholar
  47. Héthelyi É, Korány K, Galambosi B et al (2005) Chemical composition of the essential oil from rhizomes of Rhodiola rosea L. grown in Finland. J Essent Oil Res 17(6):628–629CrossRefGoogle Scholar
  48. Hooker J, Jackson B (1895–1974) Index Kewensis. Plantarum phanerogamarum nomina et synonima generum et specium. Clarendron Press, OxfordGoogle Scholar
  49. Hu X, Zhang X, Qiu S (2010) Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. Biochem Biophys Res Commun 398(1):62–67PubMedCrossRefGoogle Scholar
  50. Huang X, Zou L, Yu X (2015) Salidroside attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2a receptor related mitochondria-dependent apoptosis pathway. J Mol Cell Cardiol 82:153–166PubMedCrossRefGoogle Scholar
  51. Hung S, Perry R, Ernst E (2011) The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomized clinical trials. Phytomedicine 18:235–244PubMedCrossRefGoogle Scholar
  52. Jeong H, Ryu Y, Park S et al (2009) Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem 17(19):6816–6823PubMedCrossRefGoogle Scholar
  53. Joset K, Nyberg N, Van Diermen D et al (2011) Metabolic profiling of Rhodiola rosea rhizomes by 1H NMR spectroscopy. Phytochem Anal 22:158–165CrossRefGoogle Scholar
  54. Kenneth N, Rocha S (2008) Regulation of gene expression by hypoxia. Biochem J 414(1):19–29PubMedCrossRefGoogle Scholar
  55. Khanum F, Bawa A, Singh B (2005) Rhodiola rosea: a versatile adaptogen. Compr Rev Food Sci Food Saf 4:55–62CrossRefGoogle Scholar
  56. Kim J, Yenari M, Lee J (2015) Regulation of inflammatory transcription factors by heat shock protein 70 in primary cultured astrocytes exposed to oxygen–glucose deprivation. Neuroscience 286:272–280PubMedCrossRefGoogle Scholar
  57. Kirschke E, Goswami D, Southworth D (2014) Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles. Cell 157(7):1685–1697PubMedPubMedCentralCrossRefGoogle Scholar
  58. Kotiranta H, Uotila P, Sulkava S et al (1998) Red data book of East Fennoscandia. Ministry of the environment, Finnish environment institute and botanical museum. Finnish museum of natural history, Helsinki, p 351Google Scholar
  59. Krajewska-Patan A, Dreger M, Łowicka A et al (2007a) Chemical investigations of biotransformed Rhodiola rosea callus tissue. Herba Pol 53(4):77–87Google Scholar
  60. Krajewska-Patan A, Furmanowa M, Dreger M (2007b) Enhancing the biosynthesis of salidroside by biotransformation of p-tyrosol in callus culture of Rhodiola rosea L. Herba Pol 53(1):55–64Google Scholar
  61. Krajewska-Patan A, Dreger M, Łowicka A et al (2008) Preliminary pharmacological investigations of biotransformed roseroot (Rhodiola rosea L.) callus tissue. Herba Pol 53(4):50–58Google Scholar
  62. Kudryavtseva O, Viracheva L (2006) Results of genus Rhodiola (Crassulaceae) species introduction in Polar–Alpine Botanical Garden (Kola Peninsula). Rastit Resur 42(4):28–34Google Scholar
  63. Kurkin V, Zapesochanaya G, Shchavlinskii A (1984) Flavonoids of the rhizomes of Rhodiola rosea III. Chem Nat Compd 20(3):367–368CrossRefGoogle Scholar
  64. Kurkin V, Zapesochnaya G, Shchavlinskii A (1985) Flavonoids of the epigeal part of Rhodiola rosea I. Chem Nat Compd 20(5):623–624CrossRefGoogle Scholar
  65. Kurkin V, Zapesochnaya G, Gorbunov Y (1986) Chemical investigations on some species of Rhodiola L. and Sedum L. genera and problems of their chemotaxonomy. Rast Res 22(3):310–319Google Scholar
  66. Kurkin V, Zapesochnaya G, Nukhimovsky E et al (1988) Chemical composition of rhizomes of Mongolian Rhodiola rosea population introduced into districts near Moscow. Khim Farm Zh 22(3):324–326Google Scholar
  67. Kurkin V, Zapesochnaya G, Dubichev A (1991) Phenylpropanoids of a callus culture of Rhodiola rosea. Chem Nat Compd 27(4):419–425CrossRefGoogle Scholar
  68. Lan X, Chang K, Zheng L et al (2013) Engineering salidroside biosynthetic pathway in hairy root cultures of Rhodiola crenulata based on metabolic characterization of tyrosine decarboxylase. PLoS One 8(10):e75459PubMedPubMedCentralCrossRefGoogle Scholar
  69. Li Q, Wang H, Wang Z (2010) Salidroside attenuates hypoxia-induced abnormal processing of amyloid precursor protein by decreasing BACE1 expression in SH-SY5Y cells. Neurosci Lett 481(3):154–158PubMedCrossRefGoogle Scholar
  70. Ling-ling S, Li W, Yan-xia Z et al (2007) Approaches to biosynthesis of salidroside and its key metabolic enzymes. For Stud China 9(4):295–299CrossRefGoogle Scholar
  71. Linh P, Kim Y, Hong S et al (2000) Quantitative determination of salidroside and tyrosol from the underground part of Rhodiola rosea by high performance liquid chromatography. Arch Pharm Res 23(4):349–352PubMedCrossRefGoogle Scholar
  72. Linnaeus C (1749) Materia Medica. Liber I. De Plantis. Holmiae-Laurentii SalviiGoogle Scholar
  73. Lishmanov I, Naumova A, Afanus’ev S (1997) Contribution of the opioid system to realization of inotropic effects of Rhodiola rosea extracts in ischemic and reperfusion heart damage in vitro. Eksp Klin Farmakol 60:34–36PubMedGoogle Scholar
  74. Ma G, Li W, Dou D et al (2006) Rhodiolosides A-E, monoterpene glycosides from Rhodiola rosea. Chem Pharm Bull 54(8):1229–1233PubMedCrossRefGoogle Scholar
  75. Ma L, Liu B, Gao D et al (2007) Molecular cloning and overexpression of a novel UDP-glucosyltransferase elevating salidroside levels in Rhodiola sachalinensis. Plant Cell Rep 26:989–999PubMedCrossRefGoogle Scholar
  76. Ma L, Gao D, Wang Y et al (2008) Effects of overexpression of endogenous phenylalanine ammonia-lyase (PALrs1) on accumulation of salidroside in Rhodiola sachalinensis. Plant Biol 10:323–333PubMedCrossRefGoogle Scholar
  77. Mao G, Wang Y, Qiu Q et al (2010) Salidroside protects human fibroblast cells from premature senescence induced by H(2)O(2) partly through modulating oxidative status. Mech Ageing Dev 131(11–12):723–731PubMedCrossRefGoogle Scholar
  78. Mao J, Xie S, Zee J et al (2015) Rhodiola rosea versus ertraline for major depressive disorder: a randomized placebo-controlled trial. Phytomedicine 22:394–399PubMedPubMedCentralCrossRefGoogle Scholar
  79. Marchev A, Haas C, Schulz S et al (2014) Sage in vitro cultures: a promising tool for the production of bioactive terpenes and phenolic substances. Biotechnol Lett 36:211–221PubMedCrossRefGoogle Scholar
  80. Martin J, Pomahačová B, Dušek J et al (2010) In vitro culture establishment of Schizandra chinensis (Turz.) and Rhodiola rosea L., two adaptogenic compounds producing plants. J Phytol 2(11):80–87Google Scholar
  81. Maslova L, Kondrat’ev B, Maslov L (1994) The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Eksp Klin Farmakol 57(6):61–63PubMedGoogle Scholar
  82. Mell C (1938) Dyes, tannins, perfumes, and medicines from Rhodiola rosea. Text Colorist 60(715):483–484Google Scholar
  83. Mirmazloum I, György Z (2012) Review of the molecular genetics in higher plants towards salidrosid and cinnamyl alcohol glycosides biosynthesis in Rhodiola rosea L. Acta Aliment Hug 41:133–146CrossRefGoogle Scholar
  84. Mirmazloum I, Forgács I, Zok A et al (2014) Transgenic callus culture establishment, a tool for metabolic engineering of Rhodiola rosea L. Acta Sci Pol Hortorum Cultus 13(4):95–106Google Scholar
  85. Mirmazloum I, Ladányi M, György Z (2015a) Changes in the content of the glycosides, aglycones and their possible precursors of Rhodiola rosea during the vegetation period. Nat Prod Commun 10(8):1413–1416PubMedGoogle Scholar
  86. Mirmazloum I, Pedryc A, György Z, Komáromi B, Ladányi M (2015b) Glycoside content in Rhodiola rosea L.: dynamics and expression pattern of genes involved in the synthesis of rosavins. Acta Hortic 1098:81–89CrossRefGoogle Scholar
  87. Mirmazloum I, Radácsi P, Pedryc A et al (2015c) Hormonal effects of carbenicillin and cefotaxime on Rhodiola rosea callus culture. Planta Med 16(81):PM-243Google Scholar
  88. Morimoto R (2011) The heat shock response: systems biology of proteotoxic stress in aging and disease. Cold Spring Harb Symp Quant Biol 76:91–99PubMedCrossRefGoogle Scholar
  89. Mossberg B, Stenberg L (2003) Den nya nordiska floran. Stockholm, Wahlström and Widstrand, p 928Google Scholar
  90. Mosser D, Caron A, Bourget L et al (1997) Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 17(9):5317–5327PubMedPubMedCentralCrossRefGoogle Scholar
  91. Mudge E, Lopes-Lutz D, Brown P (2013) Purification of phenylalkanoids and monoterpene glycosides from Rhodiola rosea L. roots by high-speed counter-current chromatography. Phytochem Anal 24(2):129–134PubMedCrossRefGoogle Scholar
  92. Olsson E, Schéele B, Panossian A (2009) 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. Planta Med 75:105–112PubMedCrossRefGoogle Scholar
  93. Palumbo D, Occhiuto F, Spadaro F (2012) Rhodiola rosea extract protects human cortical neurons against glutamate and hydrogen peroxide-induced cell death through reduction in the accumulation of intracellular calcium. Phytother Res 26(6):878–883PubMedCrossRefGoogle Scholar
  94. Panossian A (2013) Adaptogens in mental and behavioral disorders. Psychiatr Clin North Am 36(1):49–64PubMedCrossRefGoogle Scholar
  95. Panossian A, Wagner H (2005) Stimulating effects of adaptogens: an overview of clinical trials of adaptogens with particular reference to their efficacy on single dose administration. Phytother Res 19(10):819–838PubMedCrossRefGoogle Scholar
  96. Panossian A, Wikman G (2009) Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol 4(3):198–219PubMedCrossRefGoogle Scholar
  97. Panossian A, Wikman G (2010) Effects of adaptogens on the central nervous system and the molecular mechanisms associated with their stress-protective activity. Pharmaceuticals 3:188–224PubMedCentralCrossRefGoogle Scholar
  98. Panossian A, Wikman G (2015) Evidence-based efficacy and effectiveness of Rhodiola SHR-5 extract in treating stress- and age-associated disorders. In: Cuerrier A, Ampong-Nyarko K (eds) Rhodiola rosea. Traditional herbal medicines for modern times. CRC Press, Taylor & Francis Group, pp 205–224Google Scholar
  99. Panossian A, Wikman G, Kaur P (2009) Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine 16(6–7):617–622PubMedCrossRefGoogle Scholar
  100. Panossian A, Wikman G, Sarris J (2010) Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine 17(7):481–493PubMedCrossRefGoogle Scholar
  101. Panossian A, Wikman G, Kaur P et al (2012) Adaptogens stimulate neuropeptide y and Hsp72 expression and release in neuroglia cells. Front Neurosci 6:6. doi: 10.3389/fnins.2012.00006 PubMedPubMedCentralCrossRefGoogle Scholar
  102. Panossian A, Hamm R, Wikman G et al (2014) Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: an interactive pathway analysis of the downstream effects using RNA microarray data. Phytomedicine 21(11):1325–1348PubMedCrossRefGoogle Scholar
  103. Petsalo A, Jalonen J, Tolonen D (2006) Identification of flavonoids of Rhodiola rosea by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1112(1–2):224–231PubMedCrossRefGoogle Scholar
  104. Platikanov S, Evstatieva L (2008) Introduction of wild golden root (Rhodiola rosea L.) as a potential economic crop in Bulgaria. Econ Bot 62(4):621–627CrossRefGoogle Scholar
  105. Punja S, Shamseer L, Olson K et al (2014) Rhodiola rosea for mental and physical fatigue in nursing students: a randomized controlled trial. PLoS One 9(9):e108416PubMedPubMedCentralCrossRefGoogle Scholar
  106. Rohloff J (2002) Volatiles from rhizomes of Rhodiola rosea L. Phytochemistry 59(6):655–661PubMedCrossRefGoogle Scholar
  107. Ross S (2014) Rhodiola rosea (SHR-5), Part I: a proprietary root extract of Rhodiola rosea is found to be effective in the treatment of stress-related fatigue. Holist Nurs Pract 28(2):149–154PubMedCrossRefGoogle Scholar
  108. Saratikov A, Krasnov E (2004) Rhodiola rosea (Golden root): a valuable medicinal plant. Tomsk University Press, Tomsk, pp 1–205Google Scholar
  109. Saunders D, Poppleton D, Struchkov A et al (2013) Analysis of five bioactive compounds from naturally occurring Rhodiola rosea in eastern Canada. Can J Plant Sci 94(4):741–748CrossRefGoogle Scholar
  110. Schriner S, Avanesian A, Liu Y et al (2009) Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses. Free Radic Biol Med 47(5):577–584PubMedCrossRefGoogle Scholar
  111. Semenza G (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3):399–408PubMedPubMedCentralCrossRefGoogle Scholar
  112. Semple H (2010) Toxicology studies on Rhodiola rosea extract. Pharm Biol 48(S1):25–32Google Scholar
  113. Shanely R, Nieman D, Zwetsloot K et al (2014) Evaluation of Rhodiola rosea supplementation on skeletal muscle damage and inflammation in runners following a competitive marathon. Brain Behav Immun 39:204–210PubMedCrossRefGoogle Scholar
  114. Shatar S, Adams R, Koenig W (2007) Comparative study of the essential oil of Rhodiola rosea L from Mongolia. J Essent Oil Res 19(3):215–217CrossRefGoogle Scholar
  115. Shi T, Feng S, Xing J et al (2012) Neuroprotective effects of salidroside and its analogue tyrosol galactoside against focal cerebral ischemia in vivo and H2O2-induced neurotoxicity in vitro. Neurotox Res 21(4):358–367PubMedCrossRefGoogle Scholar
  116. Sidjimova B, Valyovska-Popova N, Peev D (2014) Reproductive capacity of four medicinal plants in Nature Park “Rilsky Manastir”–West Bulgaria. J BioSci Biotech 177–180Google Scholar
  117. Simar D, Jacques A, Caillaud C (2012) Heat shock proteins induction reduces stress kinases activation, potentially improving insulin signaling in monocytes from obese subjects. Cell Stress Chaperon 17(5):615–621CrossRefGoogle Scholar
  118. Simeonova V, Tasheva K, Kosturkova K et al (2013) A soft computing QSAR adapted model for improvement of golden root in vitro culture growth. Biotechnol Biotechnol Equip 27(3):3877–3884CrossRefGoogle Scholar
  119. Small E, Catling M (1999) Rhodiola rosea (L.) Scop. Roseroot. In: Cavers P (ed) Canadian medicinal crops. NRC Research Press, Ottawa, pp 134–139Google Scholar
  120. Stancheva S, Mosharrof A (1987) Effect of the extract of Rhodiola rosea L. on the content of the brain biogenic monoamines. Proc Bulg Acad Sci Med 40:85–87Google Scholar
  121. Stough C, Camfield D, Kure C et al (2011) Improving general intelligence with a nutrient-based pharmacological intervention. Intelligence 39:100–107CrossRefGoogle Scholar
  122. Talalay P (2000) Chemoprotection against cancer by induction of phase 2 enzymes. BioFactors 12:5–11PubMedCrossRefGoogle Scholar
  123. Tang Y, Vater C, Jacobi A (2014) Salidroside exerts angiogenic and cytoprotective effects on human bone marrow-derived endothelial progenitor cells via Akt/mTOR/p70S6K and MAPK signaling pathways. Br J Pharmacol 171(9):2440–2456PubMedPubMedCentralCrossRefGoogle Scholar
  124. Tang H, Gao L, Mao J et al (2015) Salidroside protects against bleomycin-induced pulmonary fibrosis: activation of Nrf2-antioxidant signaling, and inhibition of NF-κB and TGF-β1/Smad-2/-3 pathways. Cell Stress Chaperon. doi: 10.1007/s12192-015-0654-4 Google Scholar
  125. Tasheva K, Kosturkova G (2010) Bulgarian golden root in vitro cultures for micropropagation and reintroduction. Cent Eur J Biol 5(6):853–863Google Scholar
  126. Tasheva K, Kosturkova G (2012a) The role of biotechnology for conservation and biologically active substances production of Rhodiola rosea: endangered medicinal species. Sci World J. doi: 10.1100/2012/274942 Google Scholar
  127. Tasheva K, Kosturkova G (2012b) Towards Agrobacterium-mediated transformation of the endangered medicinal plant golden root. AgroLife Sci J 1:132–138Google Scholar
  128. Tasheva K, Kosturkova G (2014) The effect of sucrose concentration on in vitro callogenesis of golden root-endangered medicinal plant. Sci Bull Ser F Biotechnol 18:77–82Google Scholar
  129. Taskaev A (1999) Red book of Komi Republic. Rare and endangered species of plants and animals. Design and Cartography, Moscow-Syktyvkar, p 528Google Scholar
  130. Tolonen A, Pakonen M, Hohtola A et al (2003) Phenylpropanoid glycosides form Rhodiola rosea. Chem Pharm Bull 51(4):467–470PubMedCrossRefGoogle Scholar
  131. Tolonen A, György Z, Jalonen J et al (2004) LC/MS/MS identification of glycosides produced by biotransformation of cinnamyl alcohol in Rhodiola rosea compact callus aggregates. Biomed Chromatogr 18:550–558PubMedCrossRefGoogle Scholar
  132. Troshchenko A, Kutikova G (1967) Rhodioloside from Rhodiola rosea and Rh. quadrifida. I. Chem Nat Compd 3(4):204–207CrossRefGoogle Scholar
  133. Tutin T (1964) Flora europaea. Cambridge University Press, Cambridge, p 363Google Scholar
  134. van Diermen D, Marston A, Bravo J (2009) Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol 122(2):397–401PubMedCrossRefGoogle Scholar
  135. Volkova L, Urmantseva V, Burgutin A et al (2013) Adaptogenic action of the complex of phenylpropanoids on Dioscorea deltoidea cell culture under abiotic stress. Russ J Plant Physiol 60(2):235–243CrossRefGoogle Scholar
  136. Wang H, Ding Y, Zhou J (2009) The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3. Phytomedicine 16(2–3):146–155PubMedCrossRefGoogle Scholar
  137. Weglarz Z, Przybył J, Geszprych A (2008) Roseroot (Rhodiola rosea L.): effect of internal and external factors on accumulation of biologically active compounds. In: Ramawat K, Mérillon J (eds) Bioactive molecules and medicinal plants. Springer, Berlin Heilderberg, pp 297–315CrossRefGoogle Scholar
  138. Wu Y, Lian L, Jiang Y et al (2009) Hepatoprotective effects of salidroside on fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide in mice. J Pharm Pharmacol 61(10):1375–1382PubMedCrossRefGoogle Scholar
  139. Xin T, Li X, Yao H, Lin Y, Ma X, Cheng R, Song J, Ni L, Fan C, Chen S (2015) Survey of commercial Rhodiola products revealed species diversity and potential safety issues. Sci Rep 9(5):8337CrossRefGoogle Scholar
  140. Xing S, Yang X, Li W (2014) Salidroside stimulates mitochondrial biogenesis and protects against H2O2-induced endothelial dysfunction. Oxid Med Cell Longev 2014:904834PubMedPubMedCentralCrossRefGoogle Scholar
  141. Xu J, Su Z, Feng P (1998a) Activity of tyrosol glucosyltransferase and improved salidroside production through biotransformation of tyrosol in Rhodiola sachalinensis cell cultures. J Biotechnol 61:69–73CrossRefGoogle Scholar
  142. Xu J, Liu C, Han A et al (1998b) Strategies for the improvement of salidroside production in cell suspension cultures of Rhodiola sachalinensis. Plant Cell Rep 17(4):288–293CrossRefGoogle Scholar
  143. Xu M, Gong Y, Su M et al (2011) Absence of the adenosine A2A receptor confers pulmonary arterial hypertension and increased pulmonary vascular remodeling in mice. J Vasc Res 48(2):171–183PubMedCrossRefGoogle Scholar
  144. Xu M, Shi H, Wang H et al (2013) Salidroside protects against hydrogen peroxide-induced injury in HUVECs via the regulation of REDD1 and mTOR activation. Mol Med Rep 8(1):147–153PubMedGoogle Scholar
  145. Yaglom J, Gabai V, Meriin A et al (1999) The function of HSP72 in suppression of c-Jun N-terminal kinase activation can be dissociated from its role in prevention of protein damage. J Biol Chem 274(29):20223–20228PubMedCrossRefGoogle Scholar
  146. Yousef G, Grace M, Cheng D (2006) Comparative phytochemical characterization of three Rhodiola species. Phytochemistry 67(21):2380–2391PubMedCrossRefGoogle Scholar
  147. Yu H, Ma L, Zhang J et al (2011) Characterization of glycosyltransferases responsible for salidroside biosynthesis in Rhodiola sachalinensis. Phytochemistry 72:862–870PubMedCrossRefGoogle Scholar
  148. Zapesochnaya G, Kurkin V (1982) Glycosides of cinnamyl alcohol from the rhizomes of Rhodiola rosea. Chem Nat Compd 18(6):685–688CrossRefGoogle Scholar
  149. Zapesochnaya G, Kurkin V (1983) The flavonoids of the rhizomes of Rhodiola rosea II A flavonolignan and glycosides of herbacetin. Chem Nat Compd 19(1):21–29CrossRefGoogle Scholar
  150. Zhang L, Yu H, Sun Y et al (2007) Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells. Eur J Pharmacol 564(1–3):18–25PubMedGoogle Scholar
  151. Zhang J, Liu A, Hou R et al (2009) Salidroside protects cardiomyocyte against hypoxia-induced death: a HIF-1alpha-activated and VEGF-mediated pathway. Eur J Pharmacol 607(1–3):6–14PubMedCrossRefGoogle Scholar
  152. Zhang J, Ma L, Yu H et al (2011) A tyrosine decarboxylase catalyzes the initial reaction of the salidroside biosynthesis pathway in Rhodiola sachalinensis. Plant Cell Rep 30:1443–1453PubMedCrossRefGoogle Scholar
  153. Zhang H, Shen W, Gao C et al (2012) Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer. Drugs R&D 12(2):101–106CrossRefGoogle Scholar
  154. Zhao X, Jin L, Shen N et al (2013) Salidroside inhibits endogenous hydrogen peroxide induced cytotoxicity of endothelial cells. Biol Pharm Bull 36(11):1773–1778PubMedCrossRefGoogle Scholar
  155. Zheng K, Zhang Z, Guo A et al (2012) Salidroside stimulates the accumulation of HIF-1α protein resulted in the induction of EPO expression: a signalling via blocking the degradation pathway in kidney and liver cells. Eur J Pharmacol 679(1–3):34–39PubMedCrossRefGoogle Scholar
  156. Zheng K, Sheng Z, Li Y et al (2014) Salidroside inhibits oxygen glucose deprivation (OGD)/re-oxygenation-induced H9c2 cell necrosis through activating of Akt-Nrf2 signalling. Biochem Biophys Res Commun 451(1):79–85PubMedCrossRefGoogle Scholar
  157. Zhong X, Lin R, Li Z et al (2014) Effects of salidroside on cobalt chloride-induced hypoxia damage and mTOR signaling repression in PC12 cells. Biol Pharm Bull 37(7):1199–1206PubMedCrossRefGoogle Scholar
  158. Zhou X, Wu Y, Wang X (2007) Salidroside production by hairy roots of Rhodiola sachalinensis obtained after transformation with Agrobacterium rhizogenes. Biol Pharm Bull 30(3):439–442PubMedCrossRefGoogle Scholar
  159. Zhu J, Wan X, Zhu Y et al (2010) Evaluation of salidroside in vitro and in vivo genotoxicity. Drug Chem Toxicol 33(2):220–226PubMedCrossRefGoogle Scholar
  160. Zhu Y, Shi Y, Wu D et al (2011) Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway. DNA Cell Biol 30(10):809–819PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Andrey S. Marchev
    • 1
    • 2
  • Albena T. Dinkova-Kostova
    • 3
    • 4
  • Zsuzsanna György
    • 5
  • Iman Mirmazloum
    • 5
  • Ina Y. Aneva
    • 6
  • Milen I. Georgiev
    • 1
    • 2
  1. 1.Laboratory of Applied Biotechnologies, The Stephan Angeloff Institute of MicrobiologyBulgarian Academy of SciencesPlovdivBulgaria
  2. 2.Center of Plant System Biology and BiotechnologyPlovdivBulgaria
  3. 3.Division of Cancer Research, Jacqui Wood Cancer Centre, School of MedicineUniversity of DundeeDundeeUK
  4. 4.Departments of Medicine and Pharmacology and Molecular SciencesJohns Hopkins University, School of MedicineBaltimoreUSA
  5. 5.Department of Genetics and Plant BreedingCorvinus University of BudapestBudapestHungary
  6. 6.Institute of Biodiversity and Ecosystem ResearchBulgarian Academy of ScienceSofiaBulgaria

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