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Review of adaptogenic mechanisms: Eleuthrococcus senticosus, Panax ginseng, Rhodiola rosea, Schisandra chinensis and Withania somnifera.

Objective

To identify the precise mechanisms of action of the five most common adaptogens currently used in Western Herbal Medicine in order to understand their therapeutic significance in a clinical situation.

Research design and method

Searches of data bases including MEDLINE, EMBASE, PROQUEST and EBSCO were conducted in order to isolate as many animal studies that elucidated mechanisms of action of the different adaptogens. The library catalogue of the National Herbalists Association of Australia and the E-journal catalogue at Sydney University were searched. Many relevant articles were not in English and therefore could not be included. Because this paper aims to investigate how adaptogens work rather than their efficacy and safety, articles that deal with clinical trials have been excluded. Thirty nine articles that examined mechanisms of action of Eleutherococcus senticosus, Panax ginseng, Rhodiola rosea, Schisandra chinensis and Withania somnifera were selected. These are the five most commonly used adaptogens by western herbalists, as western herbal medicine in the post modern era incorporates herbs from Chinese, Ayurvedic and other cultural traditions. The adaptive mechanisms identified in this body of articles have been organised in table form for each herb. Six of the 39 articles are reviews. They clarify the conceptual rationale for the use of adaptogens in the non-specific adaptation to stressors that may be perpetuating the disease process. Their conclusions are discussed and summarised.

Results

Adaptogenic activity was seen in all herbs. Mechanisms of action to improve adaptation to stress were as follows: E. senicocus showed activity on the HPA axis and on enzyme inhibition; P. ginseng demonstrated activity on the CNS on the HPA axis, on mitochondrial function, and demonstrated antioxidant action; Rhodiola spp demonstrated possible CNS activity, antioxidant and anti-inflammatory actions; W. somnifera demonstrated activity on the HPA axis, on the CNS and also had an antioxidant action; S. chinensis displayed antioxidant activity as its main mechanism to improve adaptation to physical stress. For a small number of studies the mechanism of action was unclear.

Conclusions

Mechanisms of action for adaptogenic activity seem to fall into 3 categories: those that act to regulate the stress response via the neuro-endocrine HPA axis, those that act as antioxidants and those that either inhibit or enhance CNS activity. Anti-inflammatory and enzyme inhibition or stimulation was also reported albeit rarely.

Introduction

In the 1940s research was conducted by the Soviet Academy of Science in Vladivostok, Siberia in order to investigate substances that were already known to increase resistance in a non-specific way. They found a strong and widespread traditional use of herbs with harmonising, tonic and adjustive actions by the well established medical systems of the world including Persian, Ayurvedic, Chinese and Japanese medicine. Although the term 'adaptogen' is a recent one and was first coined by Dr NV Lazarov in the 1950s, herbs with adaptogenic activity have existed for many centuries. Unlike conventional western medicine that treats the malady or dysfunctional system in isolation, the traditions of both Eastern and Western herbal medicine relate disease or malfunction to the whole body system including the psyche (Davydov 2000). The use of these broad acting herbs is fundamental to a holistic based therapeutic approach.

Knowledge of the mechanisms of action that improve adaptation may elucidate the specific actions and indications of adaptogens which can then be applied more reliably in a clinical situation. Panossian has reviewed both the earlier and more recent mechanisms of action of modern adaptogens. While the earlier studies focus on protein synthesis, glucose metabolism and antioxidant actions, studies from the 1990s have attributed the main mechanism of action to its effect on the neuroendocrine and immune systems that are affected and mediated by the stress response. Cortisol is recognised as a hormone common to both the endocrine and immune systems and it has been suggested that cortisol regulation by adaptogens may have an impact on both the immune and nervous systems (Panossian 1999a).

An understanding of the dynamic nature of the stress response and maintenance of "stability through change" (Spelman 2004) may also assist in understanding how adaptogens work. Adaptation occurs in response to physiological and psychological stressors including climate changes, pollution, disease and social encounters. The fundamental nature of an organism's relation to the environment sets up a dynamic where constant change or stress is being accommodated by shifts in the body's internal environment.

Allostasis describes this state where stability is maintained in the face of stress or change and is defined by neuroendocrine, autonomic nervous system and immune system activity. The burden of constant stress causes a state of allostatic load, which occurs as the necessary chemical mediators that would normally maintain stability through change fail. This prevents a smooth transition to restoration and often marks the beginnings of a slow decline in health (Panossian 1999a, Spelman 2004).

While some adaptogens reduce stress and improve immunity by intervening at the neuroendocrine level to counteract the adverse affects of excessive switch on / switch off stress responses (Panossian 1999a) the findings of Davydov (2000) in his review of the adaptogen E. senticosus led him to conclude that nonspecific resistance may occur as a result of antioxidant, anticarcinogenic, immune modulating, cholesterol lowering, hypoglycemic and choleretic actions (Davydov 2000).

Research design and methods

The five most commonly used adaptogens were chosen in order to investigate their main mechanisms of action. MEDLINE, EMBASE, EBSCO and PROQUEST were searched to find original research papers on individual mechanisms of action based on animal studies. Human trials were excluded since they focus on outcomes related to efficacy and safety rather than the actual mechanisms of action. The library catalogue of E-journals at Sydney University and the library catalogue of the National Herbalists Association of Australia were also searched.

Because research of adaptogens was first conducted by the Russians in the 1960s much of the literature is in Russian and therefore could not be included. Other relevant material was excluded due to limited access to the fully published work. As published research on adaptogens and their mechanisms of action is scarce, the search was not limited by a date of publication. Of all the adaptogens, literature on E. senticosus was the most difficult to obtain.

Results

Eleutherococcus senticosus

The original research on E. senticosus is in Russian therefore a thorough understanding of the herb has been confined to literature in English which is in itself limited. A comprehensive review by Davydov (2000) concludes that the adaptogenic effect of E. senticosus may be due to its antioxidant effect that exerts a protective and/or inhibitory action on endogenous and exogenous factors that compromise health including free radicals (Davydov 2000).

This conclusion is arrived at from various studies into the potential pharmacological actions of the plant's constituent profile and knowledge of these constituents from other plant chemistry studies.

According to these studies syringin protects against radiation, reduces radiation induced leucopenia and is immunostimulatory. Sesamin is hypocholesterolemic and has been known to reduce LDL cholesterol as well as being immunostimulatory, hepatoprotective and anticancer. [beta]-sitosterol has anticancer, antiinflammatory, antipyretic, hypocholesterolemic, antihyperglycemic actions and is insulin reducing; isofraxidin is anticancer and choleretic; caffeic acid is antioxidant; and coniferyl aldehyde has anticancer, antibacterial and antioxidant properties (Davydov 2000).

In a study by Kimura et al (2004) swimming time, natural killer (NK) activity and corticosterone levels in forced swimming stressed mice were reduced by E. senticosus root bark in which eleutheroside E was predominantly expressed (Kimura 2004). Given the knowledge that glucocorticoids play a role in adaptation to stress via the neuroendocrine pathway and immune systems (Panossian 1999a), these results support the theory that adaptogens may modify stress via an effect on the HPA axis and the sympathoadrenal system (SAS).

Another study testing the effect of E. senticosus on mast cell dependant anaphylaxis demonstrated an inhibitory effect on anti-dinitrophenyl IgE-induced production from mast cells and inhibited anaphylaxis from mast cell mediated anaphylaxis. While this shows promising results, the dose in this study was too high to be of therapeutic significance however speculation that E. senticosus may regulate mast cell granulation by stabilising membrane fluidity was postulated (Yi 2002). In his analysis of the stress response, Panossian discusses the role of corticosteroids as regulators and protectors from overreacting to stress stimuli (Panossian 1999a). Anaphylaxis can be viewed as an over reaction to a stimulus marking a failure of adaptation. In this case intervention at the corticosteroid level would be a useful modulator of the stress response.

Glucocorticoid action may also be evident in a study to test the effect of E. senticosus on the prevention of bone resorption from steroid induced osteoporosis. The urinary excretion of calcium and hyydroxyproline decreased by 3.7 - 1.4 times (5118%) respectively compared to controls (p<0.05) in vivo. These results matched treatment with Ipriflavone a synthetic daidzein derivative. Concentrations of calcium and phosphorus were also normalised in the treatment group. Breaking strength of femoral diaphyses and vertebrae increased by 42.3+29.4% in treatment group (insignificant result), but similar to ipriflavone (Kropotov 2002). These results demonstrate that E. senticocus reduces bone resorption which may lead to osteoporosis induced by corticosteroids. While the mechanism of action was not arrived at, nor was it the purpose of this study to do so, it was included because the bone resorption had been caused by excess glucocorticoids which are known to be excessive in some states of stress. E. senticosus has been shown to decrease corticosteroids as an adaptive response to stress.

Panax ginseng

P. ginseng has been researched since the 1960s in order to understand how it exerts its nonspecific action. Extrapolations from pharmacological studies have revealed that P. ginseng has a profound effect on the whole body as it aids in the resistance to stress and aging.

According to the literature reviewed in this paper the mechanisms of action that are responsible for this effect are those that resist stress via an antioxidant action, those that act on the CNS and those that regulate neuro-endocrine level pathways (Nocerino 2002).

Facino et al (1999), Sha et al (2005), Kim et al (2005) and Oliveira et al (2005) in four different studies have all associated P. ginseng with a strong antioxidant action. The prevention of myocardial damage from post ischemic reperfusion occurs according to Facino et al as P. ginseng quenches oxygen radicals, saving the heart endothelium from oxidative stress. Additionally it was proposed to stimulate the transcription of cupric zinc superoxide dismutase (Cu/Zn SOD) or coronary endothelium nitric oxide (NO) synthase and endothelial cyclic GMP (Cgmp) production of NO which is now considered to be an important antioxidant (Facino 1999).

By testing P. ginseng on a global and focal model of ischemia, Shah et al (2005) have attributed the herb's protective effect on ischemic-induced neuronal damage to an antioxidant action where lipid peroxidation is reduced and scavenger enzymes (GSH, GR, CAT, GST, [GP.sub.x] and SOD) * are increased. Lipid peroxidation (LPO) is now known to occur during stress as a nonspecific response and scavenger enzymes are believed to enhance defence of neuronal tissue leading to a reduction in damage (Shah 2005).

Kim et al (2005) also found that P. ginseng exerted an antioxidant action in a study to test its effect on exercise induced exhaustion. It was reported to have stimulated the production of CAT and SOD scavenger enzymes leading to a decrease in lipid peroxidation (Kim 2005). De Oliveira et al (2005) found P. ginseng to be protective of exercise induced muscle due to a reduction in protein oxidation.

Another indicator of the adaptive response to exercise is an increase in capillary density and mitochondrial volume. Ferrando et al (1999) found that P. ginseng exerted a similar effect to exercise on muscle oxidative capacity and capillary density however it did not have a cumulative effect when administered during exercise.

The adaptogenic effect of P. ginseng is also believed to occur due to its action on the HPA axis of the neuroendocrine pathway. According to the review by Nocerino et al (2000), adaptation is enhanced due to ginsenoside stimulation of steroidogenesis by indirectly acting on the pituitary gland. In this way it is believed to affect memory, learning and exercise endurance (Nocerino 2000). The studies of Petkov et al (1993) support this theory even though they did not set out to test the mechanism of action on stress.

Their results showed decreases in adrenaline and prolactin (in older rats) and increases in adrenocorticotrophic hormone (ACTH) in both young and old rats with P. ginseng administration. Because ACTH and adrenaline are involved in the neuroendocrine stress response these studies suggest that up or down regulation of these hormones may affect the adaptive response.

Other CNS mechanisms were observed by Provalova et al (2002), Park et al (2005) and Ni et al (1993). A reduction in bone marrow erythropoeisis during paradoxical sleep deprivation (PSD) was used as a study model to test the effect of adaptogens by Pravalova et al. P. ginseng more than the other adaptogens in this study, was seen to stimulate bone marrow erythropoeisis during PSD via modulation of neurotransmitter systems including serotonergic and cholinergic structures in the brain (Provalova 2002a).

Another study testing the neuroprotective effect of P.ginseng by Park et al (2005) on a hypoxic ischemic model revealed a protective effect that could be attributed to an increase in calmodulin-dependant kinase II (CaMKII). Finally Ni et al 1993) tested the effect of P. ginseng using a spatial working memory disruption model. P. ginseng was seen to dose dependently improve maze performance disruption and performance deficits. Interaction of P. ginseng with cholinergic function was suggested as the main mechanism of action.

Rhodiola rosea spp

Research into the adaptogenic effects of the herb has revealed that there are many different species of Rhodiola, however R. rosea is the most extensively researched. Although most of the research in this review is conducted on R. rosea, two papers on other species were included as they shed some light on the herb as an adaptogen.

In a Review by Brown et al (2002), phytochemistry and mechanisms of action are discussed at length. Hypotheses from scientific research as to how learning and memory is affected by R. rosea include activity on neurotransmitters in neuronal pathways, suppressed inhibition of acetylcholine ACh) with age associated memory loss and reduction in oxidative damage all of which are consequences of stress. Original research by Hillhouse et al (2004) supports ACh modulation as an acetylchline esterase (AChE) inhibitor which may be the mechanism of action for improved memory.

R. rosea has been seen to reduce symptoms of physically and psychiatrically induced asthenia and to increase intellectual capacity. It has been shown to improve the effects of tricyclic antidepressants TCA) and decrease their side effects. Dopaminergic activity has been suggested as a mechanism behind relieveing parkinsonian symptoms as a side effect of neuroleptics (Brown 2002).

Other reviewed studies suggested that increased resistance to nonspecific stress may be due to a serotonergic action, an increase in [beta]-endorphins and that it moderates opioid peptide, an excess of which may damage the brain and heart. R. rosea was seen to act on the neuroendocrine system similarly to other adaptogens and to have strong antioxidant properties where toxicity from drugs is decreased and some anticancer drug actions can be enhanced (Brown 2002).

Laboratory research generally confirms the above actions. Ohsugi et al (1999) isolated 19 active compounds that had oxygen scavenging activities against superoxide anion radical and hydroxyl radical. They have hypothesised that the antiaging activity may be due to oxygen scavenging molecules that reduce imbalanced redox reactions and restore defense against free radicals.

Induction of iNOS gene expression by R. sachalinensis leading to NO synthesis was another proposed mechanism of action (Seo 2001). Changes in ATP content in mitochondria are indicative of stress from exercise. Abidov et al (2004) suggested that improved tolerance to exercise in an exhaustive swimming test model may be due to stimulation of ATP production.

While Boon-niermeijer et al (2000) found R. rosea to be protective against lethal heat shock and superoxide radical, a mechanism of action could not be arrived at. The hypothesis that synthesis of stress proteins as an adaptive response was responsible for this action was excluded.

The regulatory effect of adaptogens including R. rosea, E. senticocus, Bergenia and P. ginseng on granulomonocytopoeisis may be due to neurotransmitter activity (Provalova 2002b). Additionally a study to test the effect of Astragalus and Rhodiola species on noise stress observed a reduction in hepatic glycogen, lactic acid and cholesterol which may be ultimately controlled by the HPA axis as an adaptive response (Zhu 2003).

Finally an anti-inflammatory action was seen as a mediator of adaptation as levels of C-reactive protein (CRP) and creatine kinase (CK) were reduced in untrained volunteers before exercise in treatment group (Abidov 2003).

Schisandra chinensis

According to a review by Hancke et al (1999) increases in GST in the liver and inhibition of LPO as measured by reductions in malondialdehyde (MDA) is a major antioxidant action of S. chinensis and this action may be largely responsible for its adaptogenic activity. Ip et al (1995), Zhu et al (1999) and Chiu et al (2002) have all observed modulation of the hepatic detoxification enzymes including of GST, glutathione reductase (GRD), 6-phosphate dehydrogenase and [gamma]-glutamylcysteine, Cyt P450, serum glutamic oxaloacetic transaminase (SGPT) and serum glutamic pyruvic transaminase (SGOT) and these have been associated with hepatoprotection from C[Cl.sub.4] toxicity.

Its effect on physical performance has been associated with reductions in transaminase, creatine phosphse kinase (CPK) and lactate levels as well as increases in antioxidant status measured by decreases in LPO and MDA. An anticarcinogenic effect of the herb may be due to a stimulating effect on cytP450 enzyme action and GST which are associated with the elimination of polycyclic aromatic hydrocarbons which are known carcinogens (Zhu 1999).

Kim et al (2004) observed a reduction in intracellular calcium by isolated lignins of S. chinensis alongside protection of glutamate induced toxicity. NO is driven by calcium dependant channels and is also associated with glutamate toxicity due to the generation of reactive oxygen species (ROS) by NO. A decrease of NO due to a reduction in calcium and therefore calcium dependant enzymes was the proposed mechanism of action.

Panossian et al (1999) also demonstrated a connection between S. chinensis and NO. Salivary NO was seen to increase after treatment similar to athletes and to decrease after physical exercise. In the same study a rise in cortisol similar to athletes and a decrease after physical exercise were also observed. Because NO and cortisol play a role in the switch on (NO) switch off (cortisol) phases of the neuroendocrine stress axis they may be used as markers for stress and their activation and suppression may be indicative of the adaptive process. The authors concluded from this that S. chinensis has a pro-stressor effect as NO and cortisol are stimulated in order to improve adaptation.

A study by Hernandez et al (1988) on the other hand claimed that S. chinensis had no effect on stress induced gastric ulceration which suggests that the cortisol-immune pathway may not have been affected.

In his review of S. chinensis, Hancke (1999) discusses the suggestion of a stimulating effect on the CNS and cholinergic activity as inhibition of barbiturate activity was revealed under experimental conditions. Together with antioxidant activity in the brain this may account for increased memory and intellectual performance associated with the herb.

Withania somnifera

In a review of W. somnifera by Mishra et al (2000), the authors found minimal material on the mechanisms responsible for the adaptogenic actions of the herb. Original papers using mainly animal studies however do shed some light on potential mechanisms of action that elucidate the complexity of the herb.

Kaur et al (2003) tested the adaptogenic activity of W. somnifera by administering a previously untested) withanolide compound (1-oxo-5[beta], 6[beta]-epoxy-witha-2-ene-27-ethoxy-olide) on rats in a cold-hypoxia-restraint model (C-H-R-Stress). Stress parameters were reduced in treatment group compared to controls and blood parameters revealed a decrease in CPK, lactase dehydrogenase (LDH) and LPO in treatment group compared to controls. There was also a reduction in serum corticosterone in treatment group compared to controls.

While the authors did not specifically refer to antioxidant action as such, they did conclude that an increased tolerance to stress was in part due to a decrease in CPK, LDH and LPO. A reduction in corticosterone levels during stress was also seen in treatment groups. This suggests HPA axis activity where corticosteroid levels are known to modulate the stress response and either improve or hinder adaptation.

W. somnifera was also seen to suppress OVA-specific IgE antibody and to down regulate OVA-specific IgE antibody response (Amara 1999). The IgE hypersensitivity response is an example of poor adaptation to stress.

In testing adaptogenic and cardioprotective actions as well as biochemical parameters of blood coagulation in the forced swimming test model, upregulation of anabolic processes and activity on catecholamine and mitochondrial processes was also postulated as a mechanism of action (Dhuley 2000). Battacharya et al (2002) attributed the mechanism of action to an antioxidant action rather than CNS activity in reduced symptoms in a tardive dyskinesia model.

In another study swimming time increased (p<0.01) and body weight increased (p<0.05) in treatment groups compared to controls in a mice swimming stress model. The anabolic activity of the herb was attributed to the presence of steroid compounds. W. somnifera contains steroidal lactones called withanolides. It was also postulated that the anabolic effect may be due to an anti-seratonergic activity which would lead to an increase in appetite and therefore weight gain (Grandhi 1994). In another paper Battacharya et al (2000) attributed the anxiolytic and antidepressant actions of isolated glycowithanolides to GABA-mimetic activity.

Activity on the HPA axis was postulated as a mechanism of action by Battacharya et al (2003) in a study to test the adaptogenic effect of W. somnifera on chronic stress using a footshock model. The symptoms of stress from footshock manifest in a variety of nonspecific maladies including gastric ulcer, hyperglycemia, glucose intolerance, increased plasma cortisone, sexual dysfunction in males, cognitive deficits, immunosuppression and mental depression.

For all of the above symptoms administration of W. somnifera decreased stress induced by footshock (p<0.05). While this paper does not specify exactly how, it proposes that W. somnifera acts upon the HPA axis and increases the resistance phase of the stress response in order to prevent exhaustion.

This particular test supports its reputation as having a wide ranging action that is nonspecific.

Discussion

Much of the research on adaptogens and how they improve adaptation are extrapolated from animal research that tests specific effects of the herb by using experimental models. A definitive mechanism cannot always be found. On the other hand theories derived from these studies can be useful in understanding the herb scientifically as well as learning about the stress response and the successes and failures of human and animal adaptation.

The adaptogens dealt with in this paper have demonstrated activity on the CNS and the HPA axis as well as having profound antioxidant properties. Identified actions on the CNS include neurotransmitter function (catecholamines), ACh regulation and a serotonergic effect which may be responsible for memory enhancing and cognitive function. P. ginseng and W. somnifera demonstrated this particular mechanism of action most strongly.

All of the herbs demonstrated some activity on the HPA axis including cortisol and NO regulation, catecholamine activity such as adrenalin and noradrenalin, and steroidogenesis leading to anabolic effects. Panossian (1999a) interprets the regulation of cortisol as being pivotal to an adaptogenic activity where acute administration with the herb stimulates ACTH and steroidogenesis and chronic treatment regulates stress hormones which prevents exhaustion.

W. somnifera was the only herb that demonstrated a GABA-mimetic effect which plays an important role in reducing psychological stress, a well known factor in the evolution of diseased states (Sternberg 2000).

As research into antioxidants has developed in the last 20 years, their potential in adaptation is beginning to be more understood. Antioxidant action in herbal adaptogens is associated with increased physical and mental performance and was demonstrated most strongly in P. ginseng, Rodiola spp and S. chinensis.

This review was limited by availability and accessibility to original research. This is in part due to the fact that much of the research particularly on the adaptogenic action of E. senticocus is in Russian.

Because these herbs are from cultures other than Western, much of the research exists in foreign journals that were inaccessible. Unfortunately very little attention was paid to adaptogens and their role in immunity which involves the neuroendocrine and central nervous systems where cortisol is a hormone that is common to both systems.

Nevertheless this paper does reflect some of the most current research on adaptogens shedding light on their differences and similarities.

Undergrad copy is a section for the benefit of undergraduates of herbal medicine, to encourage the contribution of the excellent work that is frequently prepared by students during the course of their studies. Student material is not subject to the peer review process of the journal and is selected on its value at presentation.

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* GSH Glutathione; GR Glutathione reductase; CAT Catalase; GST glutathione-S-transferase; GPx Glutathione peroxidase; SOD superoxide dismutase

Laura Wilson

Email companionz@bigpond.com

Laura Wilson is a recently qualified herbalist and has just opened her own herbal medicine practice called "The Herbal Tradition" in Kiama on the south coast of NSW. This literature review was her final paper in herbal medicine at Nature Care College in Sydney. Laura has a major interest in herbal medicine for animals and also runs a natural therapy centre for cats and dogs.
Proposed mechanisms of action for the adpatogenic effect of
Eleutherococcus senticocus

 Objective/method
 Herb Reference of study

E. senticocus Kropotov AV et al To test prevention of steroid
 2002 induced osteoporosis (in vivo)

 Kimura Y et al To compare E. senticocus
 2004 extracts on swimming time, NK
 activity and serum cortisone
 (in vivo)

 Yi J-M et al 2002 To test effect on mast cell
 dependent anaphylaxis
 (in vivo, in vitro)

Proposed mechanisms of action for the adpatogenic effect of Panax
ginseng

P. ginseng Facino RM et al To test the effect of P.
 1999 ginseng on HBO induced post
 ischemic reperfusion and
 endothelial function
 (in vivo, in vitro)

 Shah ZA et al To test the neuroprotective
 2005 effect of P. ginseng on
 ischemia induced brain damage
 (in vivo)

 Kim SH et al To test the effect of P.
 2005a ginseng on oxidative stress
 markers in exercise induced
 exhaustion (in vivo)

 De Oliveira AC et To test the effect of P.
 al 2005 ginseng on exercise induced
 muscle NO oxidation, muscle
 protein oxidation and
 mitochondrial changes in
 muscular damage (in vivo)

P. ginseng Ferrando et al 1999 To test the effect of P.
 ginseng on enzymatic activity,
 typical muscle composition.

P. ginseng and Petkov VD et al To test the effects of P.
Ginkgo biloba 1993 ginseng and G. biloba on
 levels of biogenic amines
 prolactin, growth hormone,
 and ACTH (in vivo)

P. ginseng, Provalova NV et al To test the effect of herbal
E. senticosus, 2002a adaptogens on erythropoesis
R. rosea, after paradoxical sleep
bergenia and deprivation (PSD)
pantohematogen

P. ginseng Park JK et al 2005 To test the neuroprotective
 effect of P. ginseng on a
 hypoxic ischemic model (in
 vivo)

 Ni XH et al 1993 To test the effect of
 P. ginseng on spatial working
 memory disruption (in vivo)

Proposed mechanisms of action for the adpatogenic effect of
Rhodiola spp.

R. rosea Hillhouse B et al To investigate potential
 2004 acetylcholine esterase (AChE)
 inhibitory effect on mental
 performance (in vitro)

R. sacra Ohsugi M et al To evaluate 70 herbal
 1999 medicines for their oxygen
 scavenging activity in the
 prevention of ageing
 (in vitro)

R. sachalinensis Seo WG et al 2001 To examine the effect of R.
 sachalinensis on expression
 of iNOS gene to induce NO
 synthase (in vitro)

R. rosea Abidov M et al To test the effect of R.
R. crenulata 2003 rosea and R. renulata on ATP
 in muscle mitochondria using
 an exhaustive swimming test
 model (in vivo)

R. rosea Boon-Niermeijer To evaluate the protective
E. senticocus EK et al 2000 effect against stress induced
 embryos of snails and the
 role of heat shock protein
 synthesis (in vitro)

R. rosea Provalova NV et al To evaluate the potential of
E. senticocus 2002b herbs to modulate
Bergenia granulocytopoiesis on neurosis
P. ginseng induced paradoxical sleep
pantohematogen deprivation PSD

Astragalus and Zhu B-W et al 2003 To test the effect of both
rhoiolae spp. herbs on hepatic glycogen,
 lactic acid and cholesterol
 during noise stress

R. rosea Abidov M et al To test the effect of R. rosea
 2004 on levels of C-reactive
 protein (CRP) and creatine
 kinase (CK) in untrained
 volunteers before/after
 exercise

Proposed mechanisms of action for the adpatogenic effect of
Schisandra chinensis

S. chinensis Ip SP et al 1995 To test the effect of
 schisandran B on glutathione
 enzyme activity with
 C[Cl.sub.4] activity (in
 vitro)


 Zhu M et al 1999 To evaluate the potential of
 S. chinensis to restore
 hepatic drug metabolism in
 C[Cl.sub.4] damaged liver
 In vivo

 Chiu PY et al 2002 To compare the antioxidant
 action of sch. B and emodin
 by testing their effect on
 hepatic mitochond. GSH with
 C[Cl.sub.4] intoxification.
 (in vivo)

 Kim SR et al 2004b To test the neuroprotective
 effect of 5 lignins from S.
 chinensis on glutamate
 induced neurotoxicity
 (in vitro)

S. chinensis Panossian AG et al To test effect on serum NO
Bryonia alba 1999b and cortisol levels during
 physical
 exercise (in vivo)

S. chinensis Hernandez DE et al To evaluate the antiulcer and
Aralia elata 1988 antisecretory activity in
 models of gastric ulcer and
 gastric secretion (in vivo)

Proposed mechanisms of action for the adpatogenic effect of Withania
somnifera

W. somnifera Kaur P et al 2003 To test the isolated
 biological fractions and
 compounds for their
 adaptogenic activity on
 stress (in vivo)

 Amara S et al 1999 To test effect on down
 regulation of antigen
 specific 1gE antibody
 response

 Dhuley JN 2000 To evaluate the adaptogenic,
 cardioprotective, and
 coagulatory effects + other
 biochemical parameters

 Battacharya SK et To test the preventive effect
 al 2002 of W. somnifera on tardive
 dyskinesia (TD)

W. somnifera Grandhi A et al To compare the efficacy of
P. ginseng 1994 both herbs on antistress
 action and anabolic activity

W. somnifera Battacharya SK et To investigate the anxiolytic
 al 2000 and antidepressant activity
 of glycowithanolides compared
 to benzodiazapene

W. somnifera Battacharya SK et To test adaptogenic activity
P. ginseng al 2003 on chronic stress--gastric
 ulcers, hyperglycemia,
 glucose intol, plasma
 cortisol, sexual dysfn,
 cognitive deficits,
 depression, immunosuppression.

 Herb Reference Intervention

E. senticocus Kropotov AV et al Liquid extract of E.
 2002 senticocus

 Kimura Y et al 5 aqueous extracts of
 2004 E. senticosus bark
 with differing
 amounts of
 eleutheroside
 A,B,C,D & E

 Yi J-M et al 2002 Aqueous extracts of
 authenticated E.
 senticosus

Proposed mechanisms of action for the adpatogenic effect of Panax
ginseng

P. ginseng Facino RM et al P. ginseng extract
 1999 G115

 Shah ZA et al P. ginseng tea
 2005 (KGT) Korean
 ginseng tea

 Kim SH et al P. ginseng extract
 2005a (50% EtOH)

 De Oliveira AC et P. ginseng extract
 al 2005 G115

P. ginseng Ferrando et al 1999 Stand. Extract
 P. ginseng G115

P. ginseng and Petkov VD et al Std. Extract of P.
Ginkgo biloba 1993 ginseng G115

P. ginseng, Provalova NV et al
E. senticosus, 2002a
R. rosea,
bergenia and
pantohematogen

P. ginseng Park JK et al 2005 Ginsenoside Rb1

 Ni XH et al 1993 Aqueous extract of
 P. ginseng

Proposed mechanisms of action for the adpatogenic effect of
Rhodiola spp.

R. rosea Hillhouse B et al Fractions of
 2004 R. rosea extract

R. sacra Ohsugi M et al
 1999

R. sachalinensis Seo WG et al 2001 Aqueous extract of
 R. sachilinensis
 (RSE)

R. rosea Abidov M et al Extracts of R. rosea
R. crenulata 2003 (rosavines and
 silidrosides 3.02%-
 0.89% dw)
 R. crenulata
 (salidroside 2.05%)

R. rosea Boon-Niermeijer Aqueous extract of
E. senticocus EK et al 2000 R. rosea and E.
 senticocus

R. rosea Provalova NV et al All herbs as aqueous
E. senticocus 2002b extracts
Bergenia pantohematogen
P. ginseng
pantohematogen

Astragalus and Zhu B-W et al 2003 Aqueous extracts of
rhoiolae spp. Rhodiolae and
 Astragali
 (spp not specified)

R. rosea Abidov M et al RHODAX/rosavine,
 2004 rosarine, rosine,
 salidroside,
 rhodalgin, rosirid-
 ine, acetylrhodalgin

Proposed mechanisms of action for the adpatogenic effect of
Schisandra chinensis

S. chinensis Ip SP et al 1995 Schisandrin B
 (Sch B) isolate

 Zhu M et al 1999 Aqueous extract of S.
 chinensis

 Chiu PY et al 2002 Schisandrin B

 Kim SR et al 2004b Dibenzocyclo-
 octadiene lignins-
 deoxyschisandrin,
 gomisin Ngomisin A,
 schisandrin,
 wuweizisu

S. chinensis Panossian AG et al S.chinensis tabs.
Bryonia alba 1999b Standardized to
 schizandrin and [gamma]-
 schizandrin

S. chinensis Hernandez DE et al Liquid extract of S.
Aralia elata 1988 chinensis 50% EtOH.

Proposed mechanisms of action for the adpatogenic effect of Withania
somnifera

W. somnifera Kaur P et al 2003 Withanolide--com-
 pound 1 (1-oxo-5[beta],
 6[beta]-epoxy-with a-2-
 ene-27-ethoxy-olide)

 Amara S et al 1999 W. somnifera extract
 (WSE)

 Dhuley JN 2000 Aqueous extract of
 authenticated
 W. somnifera root

 Battacharya SK et W. somnifera
 al 2002 glycowithanolides
 (WSG)

W. somnifera Grandhi A et al Aqu ext suspension
P. ginseng 1994 std to steroidal
 lactone in W. somnif
 & steroidal saponins
 in P. ginseng

W. somnifera Battacharya SK et W. somnifera
 al 2000 glycowithanolide

W. somnifera Battacharya SK et Aqueous extract of
P. ginseng al 2003 W. somnifera and P.
 ginseng

 Herb Reference Results

E. senticocus Kropotov AV et al [down arrow] urinary
 2002 [ca.sup.2] and hydroxyproline
 (p<0.05). Normalised plasma
 [Ca.sup.2] and Ph. [up arrow]
 Breaking strength of femoral
 diaphyses similar to
 ipriflavone.

 Kimura Y et al Eleutheroside E contributed
 2004 to recovery from fatigue,
 reduction in NK activity and
 inhibition of corticosterone
 production in swimming stress.

 Yi J-M et al 2002 Inhibited IgE induced
 TNF-[alpha]. Dose dependently
 inhibited passive cutaneous
 anaphylaxis and histamine
 release from mast cells.

Proposed mechanisms of action for the adpatogenic effect of Panax
ginseng

P. ginseng Facino RM et al P. ginseng prevented
 1999 myocardial ischemia, damage
 and impairment of end.
 Function due to [up arrow]
 ROS after HBO. L V function
 was restored and CPP was
 decreased with P. ginseng

 Shah ZA et al [down arrow] LPO and
 2005 [up arrow] scavenger enzymes
 after ischemia with KGT.
 [down arrow] brain water
 content with KGT. Reversed
 damage from acclusion and
 hypoperfusion with KGT.

 Kim SH et al [down arrow] MDA in Tx group
 2005a during exhaustive exercise
 (p<0.01) correlating with
 [up arrow] exercise
 tolerance. SOD and CAT were
 significantly increased in
 Tx group(p<0.01)

 De Oliveira AC et [down arrow] in muscle damage
 al 2005 in Tx group
 Inhibition of nitrite by
 stimulating NO synthase.
 Protected mitochondrial
 membrane injury
 in vastus and rectus muscles

P. ginseng Ferrando et al 1999 [up arrow] in capillary
 density [up arrow]
 mitochondrial content of red
 gastrocnemic muscle
 equivalent to exercise.

P. ginseng and Petkov VD et al G115 [down arrow] NA in the
Ginkgo biloba 1993 hippocampus [down arrow]
 serum prolactin, [down arrow]
 growth hormone, [up arrow]
 ACTH in old and young rats,
 [down arrow] seratonin

P. ginseng, Provalova NV et al Adaptogens prevent the
E. senticosus, 2002a [down arrow] in bone marrow
R. rosea, erythropoesis after PSD.
bergenia and Stimulated bone marrow
pantohematogen erythropoeisis during PSD

P. ginseng Park JK et al 2005 Rb1 was seen to protect
 neurons from hypoxic damage.
 [up arrow] [Ca.sup.2]/
 calmodulin dependent kinase
 II (CaMKII)

 Ni XH et al 1993 P. ginseng dose dependently
 improved maze performance
 disruption and performance
 deficits induced by stolamine

Proposed mechanisms of action for the adpatogenic effect of
Rhodiola spp.

R. rosea Hillhouse B et al R. rosea fractions inhibited
 2004 AChE by 42+3.2%.
 Fractions contained properties
 that inhibiterd AChE by 30-80%

R. sacra Ohsugi M et al 19 active compounds were
 1999 isolated and shown to have
 strong inhibitory actions
 against superoxide anion
 radical (.[O.sub.2]-) and
 hydroxyl radical (OH).

R. sachalinensis Seo WG et al 2001 RSE synergistically induced
 inos gene expression with
 [gamma]-interferon but not
 alone.

R. rosea Abidov M et al Both herbs improved swimming
R. crenulata 2003 time in exhaustive swimming
 model

R. rosea Boon-Niermeijer Both herbs demonstrated a
E. senticocus EK et al 2000 protective effect against
 lethal heat shock. Protected
 against superoxide radicals
 induced by menadione.
 Small but insignificant
 protection against copper
 and cadmium

R. rosea Provalova NV et al E. senticosus stimulated
E. senticocus 2002b migration of neutrophils from
Bergenia bone marrow to peripheral
P. ginseng P. ginseng [down arrow]
pantohematogen immature and mature
 neutrophylic granulocytesin
 bone marrow
 R. rosea and E. senticocus did
 not modify granulocytpoiesis

Astragalus and Zhu B-W et al 2003 Rhodiloa radix suppressed the
rhoiolae spp. reduction in hepatic glycogen,
 lactic acid and cholesterol

R. rosea Abidov M et al Long term treatment with
 2004 RHODAX o reduced levels of
 CRP and CK in volunteers
 undergoing exhaustive exercise

Proposed mechanisms of action for the adpatogenic effect of
Schisandra chinensis

S. chinensis Ip SP et al 1995 Pre-Tx with Sch B for 3 days
 [right arrow] [up arrow] in
 GST and GRD. [down arrow] in
 MDA was observed.
 G6PDH and [gamma]-
 glutamylcysteine were down
 regulated

 Zhu M et al 1999 [up arrow] Elimination of
 drug 1/2 life (P<0.001) and
 [down arrow] clearance time
 with pre and post
 Tx. (p<0.01) Liver enzymes
 SGPT, SGOT and P450 were
 normalized with Tx

 Chiu PY et al 2002 Sch B [right arrow] [up arrow]
 GSH AO status and mtMDA
 [right arrow] [down arrow]
 oxidative stress compared to
 [alpha]-tocopherol used as
 control.
 Sch B protected against
 C[Cl.sub.4] toxicity

 Kim SR et al 2004b Deoxyschisandrin, gomisin N
 and wuweizisu [down arrow]
 intracellular calcium,
 [up arrow] GSH defense system
 and [down arrow] cellular
 peroxide formation

S. chinensis Panossian AG et al [up arrow] basil level of
Bryonia alba 1999b salivary NO and cortisol in
 athletes in the early stage.
 After physical exercise
 salivary NO and cortisol did
 not increase in Tx group
 compared to placebo.

S. chinensis Hernandez DE et al S. chinensis had no effect
Aralia elata 1988 on stress induced ulcer and
 gastric secretionsin these
 models.
 A. elata (possibly related
 to Aralia species found in
 north America which is a
 panacea in the Native
 American herbal tradition)
 (w&w) [up arrow] gastric Ph
 and [down arrow] gastric
 secretory volume + acidity.

Proposed mechanisms of action for the adpatogenic effect of
Withania somnifera

W. somnifera Kaur P et al 2003 [down arrow] serum CPK, LDH,
 LPO and cortisol in Tx group
 compared to controls in
 chronic stress model.

 Amara S et al 1999 Down regulation of OVA
 specific IgE antibody with WSE

 Dhuley JN 2000 [up arrow] swimming time,
 heart weight and myocardial
 hepatic glycogen.
 [up arrow] duration of
 contractility after
 strophanthin K injection.
 [up arrow] coagulation time.
 Variations in hepatic
 transaminases.

 Battacharya SK et WSG inhibited haloperidol
 al 2002 induced tardive dyskinesia

W. somnifera Grandhi A et al [up arrow] swimming times
P. ginseng 1994 WS (p<0.01), PG (0.001)
 [up arrow] body weight more
 significant in WS
 (p<0.05) than PG.(0.5)
 [up arrow] levator ani muscle
 (dry weight) in both
 groups (<0.01)

W. somnifera Battacharya SK et Anxioilyic effect comparable
 al 2000 to benzodiazepine. [down
 arrow] in tribulin (marker for
 anxiety). Antidepressant
 effect comparable to ipramine
 in swimming test

W. somnifera Battacharya SK et Stress (including all of the
P. ginseng al 2003 parameters listed) induced by
 footshock was decreased
 with WS and PG (p<0.05)

 Proposed Mechanism of
 Herb Reference action (MOA)

E. senticocus Kropotov AV et al No MOA stated.
 2002 Study included possible
 relationship with
 corticosteroid levels.

 Kimura Y et al ? modulate metabolic,
 2004 inflammatory, neuroendocrine
 and immunological factors that
 regulate stress.

 Yi J-M et al 2002 E. senticosus may regulate
 degranulation of mast cells
 by stabilising membrane
 fluidity.

Proposed mechanisms of action for the adpatogenic effect of Panax
ginseng

P. ginseng Facino RM et al Protects endothelium from
 1999 oxidative burden by quenching
 [O.sub.2] radicals.
 AO action may be due to
 stimulation of coronary
 endothial NO synthase and cGMP
 NO. NO is a powerful
 antioxidant

 Shah ZA et al Neuronal protection with KGT
 2005 occurs due to antioxidant
 effect where LPO is reduced
 and scavenger enzymes (GSH,
 GR, CAT, GST, GP and SOD)
 [right arrow] [up arrow]
 defence [right arrow]
 [down arrow] damage

 Kim SH et al P. ginseng stimulates CAT
 2005a and SOD scavenger enzymes
 [right arrow] [down arrow]
 LPO [right arrow] [down arrow]
 MDA. The antioxidant action
 may contribute to [down arrow]
 fatigue and [up arrow]
 exercise tolerance.

 De Oliveira AC et The protective effect of
 al 2005 P. ginseng on damaged muscle
 (vastus, rectus) occurs due to
 improvement in mitochondrial
 function and a reduction in
 protein oxidation.

P. ginseng Ferrando et al 1999 P. ginseng may [up arrow]
 tolerance to exercise by
 [up arrow] capillary density
 and oxidative capacity of
 muscles. [up arrow] capillary
 density and [up arrow]
 oxidative capacity of muscles
 may be an adaptive process
 in [up arrow] exercise.

P. ginseng and Petkov VD et al P. ginseng may regulate
Ginkgo biloba 1993 hormones that are secreted
 in response to stress such
 as adrenalin, prolactin and
 adrenaline. In this way it
 assists adaptation.

P. ginseng, Provalova NV et al Bone marrow stimulation
E. senticosus, 2002a during PSD has been linked
R. rosea, to functional activity in
bergenia and neurotransmitter systems in
pantohematogen the brain.

P. ginseng Park JK et al 2005 Rb1 may protect neurons from
 hypoxic damage due to an
 increase in CaMKII, the
 dysregulation opf which
 results in neuronal loss
 after hypoxic damage.

 Ni XH et al 1993 P. ginseng may interact with
 cholinergic function which
 may be responsible for
 improvement in spatial
 working memory.

Proposed mechanisms of action for the adpatogenic effect of
Rhodiola spp.

R. rosea Hillhouse B et al Inhibition of AChE would
 2004 prevent the degredation
 of Ach [right arrow]
 [up arrow] memory

R. sacra Ohsugi M et al Oxygen scavenging molecules
 1999 may be responsible for
 anti-aging effect by
 scavenging excess free
 radicals [right arrow]
 [down arrow] unbalanced
 redox reactions and restore
 defence against radical
 injury to prevent aging

R. sachalinensis Seo WG et al 2001 By inducing iNOS gene
 expression, R. sachalinensis.
 Increases NO synthesis which
 is involved in the mechanism
 of non-specific immunity.

R. rosea Abidov M et al Changes in ATP content in
R. crenulata 2003 mitochodria are indicative of
 exercise induced stress.
 R. rosea and R. crenulata may
 stimulate ATP synthesis or
 re-synthesis in muscles
 during exercise

R. rosea Boon-Niermeijer Mechanism of action unclear.
E. senticocus EK et al 2000 Protection was not caused by
 synthesis of heat shock
 proteins which play a role
 in modulating heat shock and
 stress

R. rosea Provalova NV et al The regulatory effect of
E. senticocus 2002b adaptogens on
Bergenia granulocytopoiesis may occur
P. ginseng due to neurotransmitter
pantohematogen activity

Astragalus and Zhu B-W et al 2003 Because hepatic glycogen,
rhoiolae spp. lactic acid and cholesterol
 are normally reduced with
 noise stress, suppression of
 this reduction may be
 improving adaptation.

R. rosea Abidov M et al Reduction in inflammatory
 2004 mediators would suggest that
 less inflammation occurs under
 stress leading to increased
 resistance and tolerance as
 part of the adaptive process

Proposed mechanisms of action for the adpatogenic effect of
Schisandra chinensis

S. chinensis Ip SP et al 1995 [up arrow] GSH is associated
 with hepatoprotection and down
 regulation of G6PDH and
 [gamma]-glut. Improves GSH
 status.

 Zhu M et al 1999 S. chinensis has a protective
 effect on phase I oxidative
 metabolism in the liver

 Chiu PY et al 2002 Sch enhances mitochondrial
 glutathione status leading to
 improved mitochondrial GSH,GRD
 and GST [right arrow]
 [up arrow] hepatoprotection
 from C[Cl.sub.4] toxicity

 Kim SR et al 2004b NO which is driven by calcium
 dependant channels is
 associated with glutamate
 neurotoxicity due to
 [up arrow] ROS. A reduction
 in intracellular calcium may
 be responsible for [down
 arrow] NO [right arrow]
 [down arrow] glutamate
 toxicity

S. chinensis Panossian AG et al S. chinensis may have a
Bryonia alba 1999b pro-stressor effect where
 NO and cortisol, which
 play a role in the switch
 on/switch off/ phases of
 the neuroendocrine stress
 response, are being
 regulated under stress

S. chinensis Hernandez DE et al Mechanism for anti-ulcer and
Aralia elata 1988 antisecretory action of A.
 elata may act on the
 sympathetic nervous system
 which stimulates defence of
 nervous and mucosal systems
 as part of a non specific
 response.

Proposed mechanisms of action for the adpatogenic effect of
Withania somnifera

W. somnifera Kaur P et al 2003 Decreased CPK may be
 associated with [up arrow]
 [O.sub.2] delivery. May
 reduce damage to injured
 cells. May work on HPA axis
 to modulate cortisol during
 stress.

 Amara S et al 1999 No mechanism of action
 provided.

 Dhuley JN 2000 [up arrow] heart weight and
 glycogen may be indicative of
 anabolic action. [up arrow]
 coaguability may be due to
 catecholamine regulation.
 [up arrow] transaminases
 activity may be due to the
 herbs action on mitochondrial
 processes.

 Battacharya SK et Because TD was not relieved
 al 2002 by GABA-mimetic antiepileptic
 drugs but was attenuated by
 400-800 mg vit E an
 antioxidant rather than GABA-
 mimetic effect was postulated.

W. somnifera Grandhi A et al Anabolic activity may be due
P. ginseng 1994 to steroids (lactones and
 saponins). Withanolides may
 be more anabolic that
 ginsenosides. Antiseratonergic
 activity may of WS may
 [up arrow] appetite [right
 arrow] [up arrow] weight

W. somnifera Battacharya SK et Anxiolytic and antidepressant
 al 2000 action may be due to
 GABA-mimetic activity

W. somnifera Battacharya SK et Herbs may act on the HPA axis
P. ginseng al 2003 on the second stage of Selyes
 stress model in order to
 prolong resistance and
 prevent the final stage of
 exhaustion.
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Title Annotation:Undergrad copy
Author:Wilson, Laura
Publication:Australian Journal of Medical Herbalism
Geographic Code:8AUST
Date:Sep 22, 2007
Words:8834
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