Adaptogen
An adaptogen is a metabolic regulator which increases the ability of an organism to adapt to environmental factors, and to avoid damage from such factors. Environmental factors can be either physiological (external), such as injury or aging, or psychological (internal), such as anxiety.
An adaptogen must have a normalizing effect, i.e. counteracting or preventing disturbances to homeostasis brought about by stressors. Moreover, it must be innocuous with a broad range of therapeutic effects without causing any major side effects. The adaptogen concept does not fit easily into the Western model of medicine
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[edit] History of the concept
The concept adaptogen was originally created by the pharmacologist A.V. Lazarev in 1947 to describe novel effects of dibazol 12-benzyl benzimidazol, an arterial dilator developed in France.[citation needed] This concept was later (in the former Soviet Union) applied to describe remedies that increase the resistance of organisms to stress in experimental and clinical studies.[1][2][3] 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.[1][2][4]
This definition has been updated and today adaptogens are defined as a "new class of metabolic regulators which increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors."[2][4]
In spite of an extensive amount of research in the USSR, (by 1984, more than 1,500 pharmacological and clinical published studies),[4] the concept is not generally recognized in Western countries as it seemed to be in contrast to some of the key-concepts of modern pharmacology: potency, selectivity and with efficacy balanced by and accepted level of toxicity.[2][3] In 1998, however, the term adaptogen was allowed as a functional claim for certain products by US Food and Drug Administration and it is now a generally accepted concept,[2] also by the European Medicines Agency and EFSA.[5][6][7] Crude drugs that meet the criteria of being adaptogens are Eleutherococcus senticosus (Siberian ginseng), Rhodiola rosea, Schisandra chinensis and Panax ginseng.[2]
[edit] Mechanism of action
The mechanism of action has been hard to rationalize. However, by 1965 it had been demonstrated that the adaptogenic effect was dependent on the DNA-dependent synthesis of RNA.[1][4] By 1980, it was clear that the effect operated on the sympathetic nervous system.[3]
A series of recent pharmacological studies have provided a rationale for the effects at the cellular molecular level. The stress-protective activity of adaptogens has been found to be associated on the cellular level via activation molecular chaperons Hsp70,[8][9][10][11][12] and other key mediators of the stress response such as cortisol, nitric oxide, stress-activated protein kinase JNK[13] and DAF-16.[14] Heat-shock factor 1 (HSF1) and Neuropeptide Y might be primary upstream molecular targets of adaptogens in neuroglia cells.[11][12]
[edit] Repeated vs. single dose administration
The repeated administration of adaptogens gives an effect analogous to that produced by repeated physical exercise by a transition from homeostasis to heterostasis. The effect is mainly related to the HPA-axis (Hypophys-Pituitar-Adrenal-axis). Repeat dose administration of adaptogens has been shown to be of values in sports medicine and can lead to increased endurance for long distance runners, cross-country skiers etc, or to a more rapid recovery from a stressors events.[2] It should be pointed out that 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.[2][15]
Administration of adaptogens in a single dose is relevant when a rapid response to stress and strain is required. This effect is associated with the sympatho-adrenal (SAS) system. Suitable crude drugs for this purpose are Eleutherococcus senticosus (Siberian ginseng), Rhodiola rosea and Schisandra chinensis, which also can be used for repeated administration.[2]
Panax ginseng, on the other hand gives an adaptive effect only after repeated administration for periods of one to four weeks.[2]
[edit] Adaptogens as stimulants
There are important differences between the stimulating effect of adaptogens and other stimulants of the central nervous system as summarized:[2][3][16]
| Effect | Stimulant | Adaptogen |
|---|---|---|
| Recovery process after exhaustive physical load | Low | High |
| Energy depletion | Yes | No |
| Performance in stress | Decrease | Increase |
| Survival in stress | Decrease | Increase |
| Quality of arousal | Bad | Good |
| Insomnia | Yes | No |
| Side effects | Yes | No |
| DNA/RNA and protein synthesis | Decrease | Increase |
| Example | Amphetamine | Ginseng |
In contrast to conventional stimulants, such as caffeine, nicotine, amphetamine, etc, which can impair mental function and lead to addiction and tolerance with long term use, adaptogens by definition and from numerous studies do not exhibit such negative effects.[1][2][3]
One plant adaptogen that is derived from Rhodiola rosea has been shown to significantly regulate high-altitude sleep disorders and improve sleep quality. Plant adaptogens stimulate the nervous system by mechanisms which are totally different from those of traditional stimulants as associated with metabolic regulation of various elements of the stress system and modulation of stimulants-response comply.[citation needed]
[edit] References
- ^ a b c d Brekhman, II, and Dardymov, I. V. (1969). New substances of plant origin which increase nonspecific resistance. Annu Rev Pharmacol 9, 419-430.
- ^ a b c d e f g h i j k l Samuelsson, G., and Bohlin, L. Drugs of Natural Origin: A Treatise of Pharmacognosy, 6 ed., Swedish Academy of Phramaceutical Sciences, Stockholm, Sweden, 2009. Pp. 226-228.
- ^ a b c d e Fulder, Stephen (1980) [1982]. The Tao of medicine: Ginseng, Oriental remedies, and the Pharmacology of Harmony (First American ed.). New York: Destiny Books. ISBN 0-89281-027-0.
- ^ a b c d Panossian, A., Wikman, G., and Wagner, H. (1999). Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode of action. Phytomedicine 6, 287-300.
- ^ EMEA/HMPC/102655/2007. Reflection Paper on the Adaptogenic Concept. European Medicines Agency, London, 8 May 2008.
- ^ EFSA Consolidated list of Article 13 health claims of the European Food Safety Authority (EFSA) ; http://www.efsa.europa.eu/EFSA/ efsa_locale-1178620753812_article13.htm.
- ^ Legal and regulatory framework for herbal medicines. Association of the European Self-Medication Industry (AESMI). Brussells, April 2010. Pp.151-158.
- ^ Panossian, A., and Wikman, G. (2009). Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol 4, 198-219.
- ^ Panossian, A., Wikman, G., Kaur, P., and Asea, A. (2009). Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine 16, 617-622.
- ^ Panossian, A., Wikman, G., Kaur, P., and Asea, A. Molecular chaperones as mediators of stress protective effect of plant adaptogens. In: A. Asea, and B. K. Pedersen, (Eds.), Heat Shock Proteins and Whole Body Physiology, Springer, Dordrecht, The Netherlands, 2010, pp. 351-364.
- ^ a b Panossian A, Wikman G, Kaur P, Asea A. 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. 2011;77 (12), 1248.
- ^ a b Panossian, Alexander G.; Wikman, Georg; Kaur, Punit; Asea, Alexzander (13 January 2012). Malagon, Maria M.. ed. "Adaptogens stimulate neuropeptide Y and Hsp72 expression and release in neuroglia cells". Frontiers in Neuroendocrine Science (Frontiers Media S.A.) 6 (6). doi:10.3389/fnins.2012.00006. http://www.frontiersin.org/neuroendocrine_science/abstract/17819. Retrieved January 28, 2012.
- ^ 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., Surinova, S., Ytsma, E., Langelaar-Makkinje, M., Wikman, G., and Post, J. A. (2009). Plant adaptogens increase lifespan and stress resistance in C. elegans. Biogerontology 10, 27-42.
- ^ 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.
- ^ Fulder S. (1980). The Drug that builds Russians. New Scientists. 21, 83-84.
