Molecular Chaperones as Mediators of Stress Protective Effect of Plant Adaptogens

  • Alexander Panossian
  • Georg Wikman
  • Punit Kaur
  • Alexzander Asea
Part of the Heat Shock Proteins book series (HESP, volume 5)


The ability of plant adaptogens to enhance the “state of non-specific resistance” of an organism to stress by augmenting resistance to physical, biological, chemical and psychological stresses, and increasing concentration, performance and endurance during fatigue have placed it in a unique position among medicinal plants. However, the molecular mechanism by which plant adaptogens exerts its beneficial effects is thus far incompletely understood. This chapter focuses on recent advances in the understanding the molecular mechanism exerted by ADAPT-232 forte, a plant adaptogens consisting of a fixed combination of three extracts of Eleutherococcus senticocus, Schisandra chinensis and Rhodiola rosea. Our studies suggest that ADAPT-232 exerts its beneficial effect, in part, by a mechanism dependent on the upregulation of Hsp70 expression. A concise discussion of the effect of adaptogens on endurance and a comparison of hormetins and adaptogens will also be discussed


Adaptogens Eleutherococcus senticocus heat shock proteins hormesis longevity Rhodiola rosea Schisnadra chinesis 



forkhead box O transcription factor protein


forkhead box O transcription factor gene




heat shock factor-1 protein


heat shock factor-1 gene


seventy kilo Dalton stress-inducible heat shock protein


insulin-like growth factor 1


c-Jun N-terminal kinase


c-Jun N-terminal kinase kinase


lethal dose


nicotinamide adenine dinucleotide phosphate


no observable adverse effect level


RNA interference


tumor necrosis factor-alpha


time taken to exhaustion



This work was supported in part by the Swedish Herbal Institute Research and Development, Sweden (to A.P.), the USA National Institutes of Health/National Cancer Institutes grant RO1CA91889, institutional support from Scott & White Memorial Hospital and Clinic, Texas A&M Health Science Center College of Medicine, the Central Texas Veterans Health Administration and an Endowment from the Cain Foundation (to A.A).


  1. Asea, A. (2005) Stress proteins and initiation of immune response: chaperokine activity of hsp72. Exerc Immunol Rev 11, 34–45.PubMedGoogle Scholar
  2. Asea, A. (2007) Release of heat shock proteins: passive vs active release mechanisms. In: Heat Shock Proteins: Potent Mediators of Inflammation and Immunity, Vol. 1, Asea, A. and DeMaio, A. eds, pp. 3–20. Springer, Dordrecht, The Netherlands.CrossRefGoogle Scholar
  3. Asea, A. (2008) Hsp70: a chaperokine. Novartis Found Symp 291, 173–179; discussion 179–183, 221–174.CrossRefPubMedGoogle Scholar
  4. Asea, A. and De Maio, A. (2007) Heat Shock Proteins: Potent Mediators of Inflammation and Immunity, Vol. 1. Springer, Dordrecht, The Netherlands.Google Scholar
  5. Bechtold, D. A. and Brown, I. R. (2000) Heat shock proteins Hsp27 and Hsp32 localize to synaptic sites in the rat cerebellum following hyperthermia. Brain Res Mol Brain Res 75, 309–320.CrossRefPubMedGoogle Scholar
  6. Bechtold, D. A., Rush, S. J. and Brown, I. R. (2000) Localization of the heat-shock protein Hsp70 to the synapse following hyperthermic stress in the brain. J Neurochem 74, 641–646.CrossRefPubMedGoogle Scholar
  7. Brekhman, I. I. and Dardymov, I. V. (1969) New substances of plant origin which increase nonspecific resistance. Annu Rev Pharmacol 9, 419–430.CrossRefPubMedGoogle Scholar
  8. Calabrese, E. J. (2004) Hormesis: a revolution in toxicology, risk assessment and medicine. EMBO Rep 5(Suppl 1), S37–S40.CrossRefPubMedGoogle Scholar
  9. Calabrese, E. J. (2008a) Converging concepts: adaptive response, preconditioning, and the Yerkes–Dodson Law are manifestations of hormesis. Ageing Res Rev 7, 8–20.CrossRefPubMedGoogle Scholar
  10. Calabrese, E. J. (2008b) Hormesis: why it is important to toxicology and toxicologists. Environ Toxicol Chem 27, 1451–1474.CrossRefPubMedGoogle Scholar
  11. Chiu, P. Y. and Ko, K. M. (2004) Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats. Mol Cell Biochem 266, 139–144.CrossRefPubMedGoogle Scholar
  12. Diaz, G. J., Calabrese, E. and Blain, R. (2008) Aflatoxicosis in chickens (Gallus gallus): an example of hormesis? Poult Sci 87, 727–732.CrossRefPubMedGoogle Scholar
  13. Elkin, A. I. (1972) Influence of Rhodosine and Eleutherococcus extract on certain toxic effects of chlorophosis. Medicines of the Soviet Far East 11, 94–97.Google Scholar
  14. Febbraio, M. A. and Koukoulas, I. (2000) HSP72 gene expression progressively increases in human skeletal muscle during prolonged, exhaustive exercise. J Appl Physiol 89, 1055–1060.PubMedGoogle Scholar
  15. Fleshner, M. and Johnson, J. D. (2005) Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function. Int J Hyperthermia 21, 457–471.CrossRefPubMedGoogle Scholar
  16. Gabai, V. L., Mabuchi, K., Mosser, D. D. and Sherman, M. Y. (2002) Hsp72 and stress kinase c-jun N-terminal kinase regulate the bid-dependent pathway in tumor necrosis factor-induced apoptosis. Mol Cell Biol 22, 3415–3424.CrossRefPubMedGoogle Scholar
  17. Gabai, V. L., Meriin, A. B., Mosser, D. D., Caron, A. W., Rits, S., Shifrin, V. I. and Sherman, M. Y. (1997) Hsp70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance. J Biol Chem 272, 18033–18037.CrossRefPubMedGoogle Scholar
  18. Gabai, V. L., Meriin, A. B., Yaglom, J. A., Volloch, V. Z. and Sherman, M. Y. (1998) Role of Hsp70 in regulation of stress-kinase JNK: implications in apoptosis and aging. FEBS Letters 438, 1–4.CrossRefPubMedGoogle Scholar
  19. Gallucci, S. and Matzinger, P. (2001) Danger signals: SOS to the immune system. Curr Opin Immunol 13, 114–119.CrossRefPubMedGoogle Scholar
  20. Goldberg, E. D., Shubina, T. S. and Shternberg, I. B. (1971) Protective role of Eleutherococcus during the administration of rubomycia under experimental conditions. Antibiotiks 16, 113–114.Google Scholar
  21. Gonzalez, B. and Manso, R. (2004) Induction, modification and accumulation of HSP70s in the rat liver after acute exercise: early and late responses. J Physiol 556, 369–385.CrossRefPubMedGoogle Scholar
  22. Hackenberger, B. K., Jaric-Perkusic, D. and Stepic, S. (2008) Effect of temephos on cholinesterase activity in the earthworm Eisenia fetida (Oligochaeta, Lumbricidae). Ecotoxicol Environ Saf 71, 583–589.CrossRefPubMedGoogle Scholar
  23. Hacker, B. and Medon, P. J. (1984) Cytotoxic effects of Eleutherococcus senticosus aqueous extracts in combination with N6-(delta 2-isopentenyl)-adenosine and 1-beta-D-arabinofuranosylcytosine against L1210 leukemia cells. J Pharm Sci 73, 270–272.CrossRefPubMedGoogle Scholar
  24. Heydari, A. R., Takahashi, R., Gutsmann, A., You, S. and Richardson, A. (1994) Hsp70 and aging. Experientia 50, 1092–1098.CrossRefPubMedGoogle Scholar
  25. Ip, S. P., Che, C. T., Kong, Y. C. and Ko, K. M. (2001) Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver. Cell Stress Chaperones 6, 44–48.CrossRefPubMedGoogle Scholar
  26. Kaur, P., Panossian, A., Wikman, G., and Asea, A. 2010. Efficacy of Adaptogens in animal tumors: a pilot study (in preparation).Google Scholar
  27. Khasina, E. I., Dardymov, I. V., Brekhman, I. I. (1983) Effect of Eleutherococcys extract on the readaptation processes after 7-hour hypokinesia in rats. Kosm Biol Aviakosm Mod. 17, 55–58.Google Scholar
  28. Lancaster, G. I. and Febbraio, M. A. (2005) Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72. Exerc Immunol Rev 11, 46–52.PubMedGoogle Scholar
  29. Mattson, M. P. (2008a) Dietary factors, hormesis and health. Ageing Res Rev 7, 43–48.CrossRefPubMedGoogle Scholar
  30. Mattson, M. P. (2008b) Hormesis defined. Ageing Res Rev 7, 1–7.CrossRefPubMedGoogle Scholar
  31. Mattson, M. P., Son, T. G. and Camandola, S. (2007) Viewpoint: mechanisms of action and therapeutic potential of neurohormetic phytochemicals. Dose Response 5, 174–186.CrossRefPubMedGoogle Scholar
  32. Matzinger, P. (1998) An innate sense of danger. Semin. Immunol. 10, 399–415.CrossRefPubMedGoogle Scholar
  33. Medon, P. J., Thompson, E. B. and Farnsworth, N. R. (1981) Hypoglycemic effect and toxicity of Eleutherococcus senticosus following acute and chronic administration in mice. Zhongguo Yao Li Xue Bao 2, 281–285.PubMedGoogle Scholar
  34. Mikhailova, L. I. and Fruentov, N. K. (1972) Influence of Eleutherococcus and Hedera colchica on organism resistance to respiratory poisons and some aspects of thyroidine action. Medicines of the Soviet Far East 11, 86–90.Google Scholar
  35. Monakhov, B. V. (1965) Influence of the liquid extract from the roots of Eleutherococcus senticosus on toxicity and antitumor activity of cyclophosphane. Vopr Oncl 11, 60–63.Google Scholar
  36. Monakhov, B. V. (1967a) The effect of Eleutherococcus senticosus maxim on the therapeutic activity of cyclophosphane, ethymidine, and benzo-TEPA. Vopr Oncl 13, 94–97.Google Scholar
  37. Monakhov, B. V. (1967b) The reduction of the toxic effect of some antiblastomic preparations with the Eleutherococcus extract. Vopr Oncl 13, 71–76.Google Scholar
  38. Morley, J. F. and Morimoto, R. I. (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15, 657–664.CrossRefPubMedGoogle Scholar
  39. Mosser, D. D., Caron, A. W., Bourget, L., Meriin, A. B., Sherman, M. Y., Morimoto, R. I. and Massie, B. (2000) The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Molecular and Cellular Biology 20, 7146–7159.CrossRefPubMedGoogle Scholar
  40. Narimanian, M., Badalyan, M., Panosyan, V., Gabrielyan, E., Panossian, A., Wikman, G., Wagner, H. (2005) Impact of ChisanR (ADAPT 232) on the quality of life and its efficacy as an adjuvant in the treatment of acute non-specific pneumonia”, Phytomedicine, 12, 723–729.CrossRefPubMedGoogle Scholar
  41. Olsson, E. M. G., von Scheele, B. and Panossian, A. (2008) A randomized double-blind placebo controlled parallell group study of SHR-5 extract of Rhodiola rosea roots as treatment for patients with stress related fatigue. Planta Med. (in press).Google Scholar
  42. Panossian, A. (2003) Adaptogens: tonic herbs for fatigue and stress. Alt Comp Therap 9, 327–332.CrossRefGoogle Scholar
  43. Panossian, A. (2005) Effect of adaptogens on the central nervous system. Arq Bras Fitomed Cient 2, 108–130.Google Scholar
  44. Panossian, A., Hambartsumyan, M., Hovanissian, A., Gabrielyan, E. and Wilkman, G. (2007) The adaptogens Rhodiola and Schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol. Drug Turgets Instights 1, 39–54.Google Scholar
  45. Panossian, A., Nikoyan, N., Ohanyan, N., Hovhannisyan, A., Abrahamyan, H., Gabrielyan, E. and Wikman, G. (2008) Comparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine 15, 84–91.CrossRefPubMedGoogle Scholar
  46. Panossian, A. and Wagner, H. (2005) Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother Res 19, 819–838.CrossRefPubMedGoogle Scholar
  47. Panossian, A. and Wikman, G. (2008) Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol 118, 183–212.CrossRefPubMedGoogle Scholar
  48. Panossian, A. G., Oganessian, A. S., Ambartsumian, M., Gabrielian, E. S., Wagner, H. and Wikman, G. (1999) Effects of heavy physical exercise and adaptogens on nitric oxide content in human saliva. Phytomedicine 6, 17–26.PubMedGoogle Scholar
  49. Pashinian, S. A., Panossian, A. G., Gasparian, G. V., Jahatspanian, I. G., Nikishenko, M. N., Avetissian, G. M. and Mnatsakanian, V. A. (1981) Cucurbitacine glucosides and trihydroxyoctadecadienoic acids-new tonic compounds from Bryonia alba L. roots. In: New Data About Eleuterococcus and Other Adaptogens, pp. 149–154. DVNC of AN USSR, Vladivostok.Google Scholar
  50. Powers M. V., Workman, P. (2007) Inhibitors of the heat shock response: biology and pharmacology. FEBS Letters, 581, 3758–3769.CrossRefPubMedGoogle Scholar
  51. Stukov, A. N. (1966) Combined action of Eleutherococcus senticosus and sarcolysin on lymphosarcoma LIO-I in mice. Vopr Oncl 12, 57–60.Google Scholar
  52. Tsyrlina, E. V. (1965) Influence of chemotherapeutic agents combined with the extract of Eleutherococcus senticosus on rise and development of the “SSK” tumour metastases. Vopr Oncl 11, 70–77.Google Scholar
  53. Tuomisto, J., Pekkanen, J., Kiviranta, H., Tukiainen, E., Vartiainen, T., Viluksela, M. and Tuomisto, J. T. (2006) Dioxin Cancer Risk – Example of Hormesis? Dose Response 3, 332–341.CrossRefPubMedGoogle Scholar
  54. Volloch, V., Mosser, D. D., Massie, B. and Sherman, M. Y. (1998) Reduced thermotolerance in aged cells results from a loss of an Hsp72-mediated control of JNK signaling pathway. Cell Stress Chaperones 3, 265–271.PubMedGoogle Scholar
  55. Wagner, H., Hikino, H. and Farnsworth, N. R. (1985) Economic and Medicinal Plant Research. Vol. 1, pp. 156–215. Academic Press Inc, London.Google Scholar
  56. Wagner, H. and Proksch, A. (1985) Immunostimulatory drugs of fungi and higher plants, Vol. 1. Academic Press Inc, London.Google Scholar
  57. Westerheide, S.D., and Morimoto, R.I. (2005) Heat shock response modulators as therapeutic tools for diseases of protein conformation. J. Biol. Chem. 280, 33097–33100.CrossRefPubMedGoogle Scholar
  58. Whitham, M. and Fortes, M. B. (2008) Heat shock protein 72: release and biological significance during exercise. Front Biosci 13, 1328–1339.CrossRefPubMedGoogle Scholar
  59. Wiegant, F. A., Surinova, S., Ytsma, E., Langelaar-Makkinje, M., Wikman, G. and Post, J. A. (2008a) Plant adaptogens increase lifespan and stress resistance in C. elegans. Biogerontology (in press).Google Scholar
  60. Wiegant, F. A. C., Limandjaja, G., de Poot, S. A. H., Bayda, L. A., Vorontsova, O. N. and Zenina, T. A. (2008b) Plant adaptogens activate cellular adaptive mechanisms by causing mild damage. In: Adaptation Biology and Medicine: Health Potentials, Vol. 15, Lukyanova, L., Takeda, N. and Singal, P. K. eds, pp. 319–332. Narosa Publishers, New Delhi, India.Google Scholar
  61. Yang, P., He, X. Q., Peng, L., Li, A. P., Wang, X. R., Zhou, J. W. and Liu, Q. Z. (2007) The role of oxidative stress in hormesis induced by sodium arsenite in human embryo lung fibroblast (HELF) cellular proliferation model. J. Toxicol. Environ. Health A 70, 976–983.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Alexander Panossian
    • 1
    • 2
  • Georg Wikman
    • 1
  • Punit Kaur
    • 3
  • Alexzander Asea
    • 3
  1. 1.Swedish Herbal Institute Research and DevelopmentÅsklosterSweden
  2. 2.Swedish Herbal Institute Research and DevelopmentÅsklosterSweden
  3. 3.Division of Investigative PathologyThe Texas A&M Health Science Center College of Medicine, Scott & White Memorial Hospital and ClinicTempleUSA

Personalised recommendations