||This article may present fringe theories, without giving appropriate weight to the mainstream view, and explaining the responses to the fringe theories. (December 2012)|
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Adaptogens or adaptogenic plants, herbs(I.e, Ginseng) or refer to the pharmacological concept whereby administration results in stabilization of physiological processes and promotion of homeostasis, for example decreased cellular sensitivity to stress. The European Medicines Agency states in a 2008 reflection paper that the concept requires additional clinical and pre-clinical research, and is therefore not accepted into canonized terminology.
In general, pharmacological theory abides by the receptor theory of drug mechanism, and the scientific community calls into question the validity of the concept of adaptogens, while the FDA and European Medicines Agency accept the concept in theory. In herbal medicine, the categorization of different herbs as adaptogens is very popular, often with far-reaching claims of increasing longevity, libido, and well-being. Most of the studies conducted on adaptogens were performed in the Soviet Union, Korea, and China during the 1980s, and are at large not considered conclusive, having been criticized for reasons including methodological flaws. Adaptogens have been claimed to treat a wide variety of medical conditions, from fatigue to cancer. However, no herbs that are considered adaptogens by the Food and Drug Administration (FDA) have ever been conclusively shown effective in treating medical conditions, and as a result none of them are approved by the U.S. FDA to cure, treat, or prevent disease. Adaptogenic effect of some herbs may hold certain merit on account of the ability of the substances to increase the bodies own response to oxidative stress, such as gynostemma pentaphyllum or poor-man's ginseng, which has been shown to increase the body's innate response by increased production of superoxide dismutase (SOD). SOD mimetics such as TEMPOL are currently being researched.
The concept of adaptogens was originally created by pharmacologist N.V. Lazarev in 1947 to describe novel effects of dibazol 12-benzyl benzimidazol, an arterial dilator developed in France. Adaptogenesis was later (in the former Soviet Union) applied to describe remedies that increase the resistance of organisms to biological stress in experimental and clinical studies. According to the original definition, adaptogens are:
non-specific remedies "that increase resistance to a broad spectrum of harmful factors (stressors) of different physical, chemical and biological natures".
This definition has been updated, and today adaptogens are conceptualized as a:
"new class of metabolic regulators (of a natural origin) which increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors."
An extensive amount of research was conducted in the USSR, (by 1984, more than 1,500 pharmacological and clinical published studies),. Adaptogens have even been described as "medicine[sic] for healthy people". In 1998, however, the term adaptogen was allowed as a functional claim for certain products by US Food and Drug Administration and the European Medicines Agency claims The concept of adaptogens is sufficient to be considered in the assessment of traditional herbal medicinal products (e.g. monograph on Eleutheroccocus root).
Adaptogens in other cultures
The concept of adaptogens as "medicine for the healthy" or in helping the body cope with stress is a great deal similar to many remedies common in chinese herbology, as well as other forms of traditional medicine.
Ayurveda traditional medicine operates with the concept of rasayana. Various substances are classified in this tradition as rasayanas, meaning that they are believed to promote physical and mental health, improve defense mechanisms of the body, and enhance longevity. Rasayanas are referred to as adaptogens by some researchers. 
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The mechanism of action of adaptogens has been hard to rationalize. However, by 1965, it had been demonstrated that the adaptogenic effect is dependent on cellular transcription By 1980, it was clear that the effect operates on the sympathetic nervous system.
A series of recent pharmacological studies have provided rationale for the effects at the molecular level. The stress-protective activity of adaptogens has been found to be associated with activation of molecular chaperonin Hsp70, and other key mediators of the stress response such as cortisol, nitric oxide, stress-activated protein kinase JNK and DAF-16. Studies have demonstrated that heat-shock factor 1 (HSF1) and Neuropeptide Y might be primary upstream molecular targets of adaptogens in neuroglia cells, but the results were only suggestive not conclusive. One recent analysis revealed that a claimed adaptogen extract ADAPT-232, and some of its components individually, regulates the transcription of genes involved in cellular signaling pathways, the most notable ones being those of G protein-coupled receptors.
Repeated vs. single-dose administration
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The stress-protective effect by repeated intake is not the result of inhibition of the stress response but of adaptive changes in the organism to the repeated stress-mimetic effect of the drug. Adaptogens are stress agonists and not stress-antagonists.
Adaptogens vs. stimulants
|This section's factual accuracy is disputed. (January 2014)|
In spite of their theoretical normalizing effect, certain dosing regimens of supposed adaptogenic plant extracts are claimed to have stimulating effects on the central nervous system. Plant adaptogens are said to stimulate the nervous system by mechanisms that are totally different from those of conventional stimulants as associated with metabolic regulation of various elements of the stress system and modulation of stimulants-response comply.[clarification needed] Adaptogens are also claimed to be efficacious in the treatment of anxiety disorders.
List of plants with purported adaptogenic effects
Note: This is a list of plants only claimed to have adaptogenic effects. It does not constitute a list of substances safe for administration or having no interactions with other medicines!
|Plant||Effect from single dose?||Effect from repeated dose?|
|Eleutherococcus senticosus (Siberian ginseng)|
|Rhodiola rosea||Yes||Yes|
|Schisandra chinensis||Yes||Yes|
|Panax ginseng||No (effect after 1–4 weeks)||Yes|
|Gynostemma pentaphyllum (Jiao Gu Lan)|
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- EMEA/HMPC/102655/2007. Reflection Paper on the Adaptogenic Concept. European Medicines Agency, London, 8 May 2008.
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- Lesser, Frank (18 September 1980). "Letters: Eleutherococcus". New Scientist 87 (1219): 885. Retrieved 10 January 2013. "Soviet authors in this field ... lay emphasis not on the treatment of disease but on the use of eleutherococcus and ginseng among others 'as medicines for healthy people', as Professor Brekhman said in a lecture at Chelsea College last year."
- Indian J Exp Biol. 2000 Feb;38(2):119-28. http://www.ncbi.nlm.nih.gov/pubmed/11218827
- Phytother Res. 1999 Jun;13(4):275-91. http://www.ncbi.nlm.nih.gov/pubmed/10404532
- Panossian, A.; Wikman, G. (September 2009). "Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity". Current Clinical Pharmacology 4 (3): 198–219. doi:10.2174/157488409789375311. PMID 19500070.
- Panossian, A.; Wikman, G.; Kaur, P.; Asea, A. (June 2009). "Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones". Phytomedicine 16 (6–7): 617–622. doi:10.1016/j.phymed.2008.12.003. PMID 19188053.
- Panossian, A.; Wikman, G.; Kaur, P.; Asea, A. (2010). "Molecular Chaperones as Mediators of Stress Protective Effect of Plant Adaptogens". Heat Shock Proteins and Whole Body Physiology. Heat Shock Proteins 5. Springer. pp. 351–364. doi:10.1007/978-90-481-3381-9_20. ISBN 978-90-481-3380-2.
- Panossian, A; Wikman, G; Kaur, P; Asea, A. (2011). "Adaptogens (ADAPT-232) stimulate neuropeptide Y expression in neuroglia cells. 59th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research, 4th-9th September 2011, Anatalya, Turkey". Planta medica 77 (12): 1248.
- Panossian, Alexander G.; Wikman, Georg; Kaur, Punit; Asea, Alexzander (2012). "Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells". Frontiers in Neuroscience 6: 6. doi:10.3389/fnins.2012.00006. PMC 3269752. PMID 22347152.
- 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 Targets Instights 1, 39-54.
- Wiegant, F. A. C.; Surinova, S.; Ytsma, E.; Langelaar-Makkinje, M.; Wikman, G.; Post, J. A. (February 2008). "Plant adaptogens increase lifespan and stress resistance in C. Elegans". Biogerontology 10 (1): 27–42. doi:10.1007/s10522-008-9151-9. PMID 18536978.
- Panossian, Alexander G.; Hamm, Rebecca; Kadioglu, Onat; Wikman, Georg; Efferth, Thomas (2013). "A1. Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells.". Frontiers in Neuroscience 7: 16. doi:10.3389/fnins.2013.00016. PMID 23430930.
- Panossian, A.; Wagner, H. (October 2005). "Stimulating effect of adaptogens: An overview with particular reference to their efficacy following single dose administration". Phytotherapy Research 19 (10): 819–838. doi:10.1002/ptr.1751. PMID 16261511.
- A. Panossian and G. Wikman (2005), "Effect of adaptogens on the central nervous system", Arquivos Brasileiros de Fitomedicina Científica 3: 29-51)