throughout the 70 s of the 20th century , investigations on a new class of pharmacologically active substances actoprotectors ( aids for improving human s physical and mental efficiency ) were guided by professor vladimir vinogradov .
these investigations resulted from the development of the first and the most commonly used actoprotector , bemitil ( chemical structure 2-ethylbenzimidazole hydrobromide ) ( fig .
1 ) . later , other actoprotectors were created , such as bromantane . for the last 20
yr , people synthesized and studied other compounds with actoprotecive properties belonging to different chemical classes : thiazoloindole derivatives , 3-hydroxypyridine derivatives , nicotinic acid derivatives , 1-oxa-4-aza-2-silacyclanes etc [ 3 - 5 ] . at the same time , experimental studies and analyses of pharmacological properties of certain herbs proved that some phytochemicals , while having a very low toxicity , are also aids that improve human s physical and mental efficiency . among such herbs ,
there are interesting plant adaptogens : panax ginseng and other species from genus panax , eleutherococcus senticosus , pfaffia paniculata , withania somnifera , schisandra chinensis , gynostemma pentaphyllum , rhodiola rosea , etc .
actoprotectors are preparations that enhance the body stability against physical loads without increasing oxygen consumption or heat production , increasing the efficiency factor .
actoprotectors fall under the metabolic drugs of non - consumptive class of action and possibly possessing antihypoxic characteristics at either higher or lower extent .
the agents differ from antihypoxants since actoprotectors primarily stimulate protein synthesis and increase working capacity . moreover
, the preparations exert an antihypoxic effect under hypoxic conditions , which may advance as a result of mitochondrion - decreased ability to oxidize substrates under higher physical loads . however , this is not the case in hypoxic conditions of other etiology .
the principal difference of actoprotectors and psychostimulants ( caffeine , sydnocarb , phenamine , methylphenidate , modafinil , adrafinil etc . ) is that actoprotectors are agents of non - exhaustive actions . in actions of actoprotectors
, there is no increase in oxygen consumption or heat production ; differing with nootropic agents  actoprotectors increase not only mental , but physical work capacity as well .
vinogradov presumed that actoprotectors did not have enough theoretical background to be labeled as a new class of pharmacological compounds .
this separation appeared as a result of development of military medicine to improve physical strength .
our opinion about this connection is that the actoprotectors are considered as synthetic ( and possibly , natural origin ) adaptogens with strong positive influence on physical work capacity .
it means , for the convenience of pharmacological classification , some synthetic adaptogens that highly increase the physical performance can be determined as 
for example , benzimidazole derivatives dibazol ( bendazol ) , levamisole and afobazol are all regarded in scientific literature as adaptogens .
dibazol s adaptogenic action was initially realized in adaptation in difficult environment conditions through immune mechanisms [ 18 - 27 ] .
levamisole s adaptogenic activity is also connected primarily with adaptive changes in the immune system [ 28 - 31 ] .
afobazol has neuroprotective properties established in vitro on survival of ht-22 neurons in the model of oxidative stress and glutamate toxicity , and its adaptogenic action was determined through central nervous system adaptation [ 33 - 35 ] . since benzimidazole derivatives have adaptogenic properties , these compounds are similar to bemitil , but their influence on physical work capacity is either absent or minimal .
we think that briefly , actoprotectors can be mentioned as  synthetic or natural origin adaptogens with significant capacity to increase physical and mental performance. the classic reference actoprotector is bemitil ; in its chemical structure , bemitil is 2-ethylthiobenzimidazole hydrobromide ( fig .
currently , only two compounds , among all actoprotectors , are permitted for medical administration : bemitil ( commercial name antihot , certified in ukraine as dietary supplement ) and bromantane ( commercial name ladasten , certified in russia as a drug ) ( fig .
1 ) . adaptogenic herbs are more available all over the world . in many countries
it becomes more convenient in the usage for people with active lifestyle or whose professional activity is related with heavy physical and/or mental loads ( athletes , military service men , firefighters , crew members , computer operators , night shift doctors and nurses , etc . ) .
therefore , adaptogenic herbs as potential actoprotectors have not just only theoretical importance for the understanding of mechanisms of their pharmacological action , but also practical applications in sport and occupational medicine .
a primary analysis of actoprotector s effect under heavy physical loads observed its influence on carbohydrates and energy metabolism : slight decreases of glycogen and creatine phosphate content in the liver and muscles , and of glucose in the blood and lower accumulation of lactates in the tissues and blood , and lower increases in heat production and oxygen consumption .
after the period of exertion ended , rehabilitation of the factors under study was accelerated , and indeed , some factors showed super compensation .
2 illustrates the influence of benzimidazole actoprotector on glycogen content in rat liver during recovery .
interestingly , the 4 hour time - point showed a reversed pattern for all of the parameters .
the authors assumed that at this point of the recovery period , the energy resources are expended on different biosynthetic processes , leaving the energy supply for muscular activity is severely limited .
thus , in this situation ,  switching  of intracellular metabolism to the anabolic reactions , rather than catabolic predominantly , occurs .
this is why the work capacity settles at a relatively low level and can not be increased using pharmacological agents .
noted the increase of the heart and not the liver glycogen content by the 4th hour of the recovery period , and drew conclusions about the importance of the liver glycogen content to the capacity for work .
however , this phenomenon reflects a more complex mechanism that can not be explained on the aforementioned basis alone and requires further research .
the significant decrease of total rna content in the 4th hour of the recovery period in liver under benzimidazole actoprotector administration is believed to be the evidence behind this reasoning ( fig .
it has been established that the therapeutic effect of actoprotectors ( bemitil , as an example ) is a function of its complex mechanism entailing cell genome activation , optimization of mitochondrial oxidation , oxidative stress reduction , and stimulation of cellular immune response .
recently p. ginseng ( known also as ginseng and korean ginseng ) is one of the most well - known and studied adaptogens .
it is grown in china , korea , japan , and russia while having a long - time ( some thousands years ) history of its administration in oriental medicine .
nowadays , p. ginseng as a dietary and medicinal custom is not only in asia ( especially korea and china ) , but is also used world - wide .
ginseng is available in many forms : whole root , root powder ( white ginseng ) , steamed root powder ( red ginseng ) , heat processed root powder ( sun ginseng ) , steamed and dried roots for 5 d and 9 times respectively ( black ginseng ) , teas , tinctures , and standardized root extracts containing known and reproducible amounts of ginseng saponins in every batch [ 37 - 40 ] . in some countries ,
other species from genus panax ( p. bipinnatifidus , p. japonicus , p. notoginseng , p. pseudoginseng , p. quinquefolius , p. stipuleanatus , p. trifolius , p. vietnamensis , p. wangianus , p. zingiberensis ) are not as well - known as p. ginseng , but they are also used in oriental medicine . among the diverse constituents of ginseng , steroid - like phytochemicals with adaptogenic properties named ginsenosides have been found to be major components responsible for their biological and pharmacological actions .
ginsenosides are a special group of triterpenoid saponins that can be classified into two main groups by the skeleton of their aglycones : panaxadiol group ( rb1 , rb2 , rb3 , rc , rd , rg3 , rh2 , and rs1 ) and panaxatriol group ( re , rf , rg1 , rg2 , and rh1 )   ( fig .
more than 150 naturally occurring ginsenosides have been isolated from roots , leaves / stems , fruits , and/or flower buds of ginseng .
ginsenosides have been the target to many researches as they are believed to be the main active components behind the claims of ginseng s efficacy .
these steroid - like phytochemicals , which are known to counter the negative influence of stress , are beneficial for health property .
the glycosides act on the adrenal glands , helping to prevent adrenal hypertrophy and excess corticosteroid production in response to stress .
ginseng stimulates the formation of blood vessels and improves blood circulation in the brain , thereby improving memory and cognitive abilities .
ginseng is also used as treatments of diabetes , migraines , infections , cancer , radiation and chemotherapy protection , sleep aid , and appetite stimulation [ 42 - 44 ] .
the ginsenosides content in ginseng preparations can vary depending on the species , the age , portion of the plant , the preservation method , the season of harvest , and the extraction method [ 45 - 47 ] .
for example , comparative study on the ginsenosides of 47 samples of ginseng products derived from different panax species was conducted using a reverse - phase hplc method .
the results showed that the ginsenoside compositions in ginseng products of different origins were considerably variable .
chikusetsu - ninjin derived from p. japonicus ( japan ) was found to have the highest content ( 192.80 - 296.18 mg / g ) and a product from p. ginseng to be the lowest ( 5.78 - 15.63 mg / g ) .
two main groups suggested by phytochemical data were clearly observed : group i mainly containing dammarane saponins consisted of p. ginseng , p. quinquefolius , p. notoginseng , p. vietnamensis and p. vietnamensis var .
fuscidiscus and group ii containing a large amount of oleanolic acid saponins was composed of p. japonicus ( japan ) , p. zingiberensis , p. japonicus ( china ) , p. japonicus var .
the ratios of the subtotal of dammarane saponins to that of oleanolic acid saponins were found to be > 1.9 and < 0.25 for groups i and ii , respectively .
the product samples derived from the same botanical origin revealed similar constituent patterns , in other words , each panax taxon showed its own characteristic chromatographic profile , which appeared in the specific shape of an 11-direction radar graph constructed on the basis of the result of quantitative analysis .
similarities of chemical constitution were seen among the closely phylogenetically - related taxa , including p. ginseng and p. quinquefolius , p. vietnamensis and p. vietnamensis var .
fuscidiscus , p. japonicus ( china ) and its varieties , except for p. japonicus ( japan ) and p. zingiberensis 
 .
as mentioned above , except for ginsenosides , plants from genus panax contain other active compounds ( carbohydrates including polysaccharides , vitamins , alkaloids , fat soluble components , organic acids , microelements and macroelements , etc . ) which make important contributions in their pharmacological activity , but the quantity and composition of these compounds differ among the different species [ 49 - 53 ] . all together
these facts explain why pharmacological properties of plants from genus panax are similar , but not the same ; moreover , pharmacological activity of different preparations from the same part ( roots , leaves etc . )
of the same species can be different depending on the season of harvest and the extraction method .
finally , differences between different ginseng preparations can have an influence not just only in their potency , but also in kinds of their pharmacological activity .
recently , the most widely standardized ginseng extracts , both commercially and for research purposes , are g115   and products of korea ginseng corporation ( seoul , korea ) , concentrated aqueous extracts from p. ginseng root , which are standardized to contain a certain amount of ginsenosides .
poor standardization can cause difficulties in evaluation of data received from the animal experiments and human studies related with pharmacological activity of adaptogens including ginseng .
it means that sometimes data from different laboratories connected with pharmacological properties ( including neurocognitive and actoprotective activity ) of preparations from the same species can not be compared ( or , at least , their comparison is very complicated ) . in conclusion
, data on pharmacological activity of preparations received from different species from genus panax should be evaluated separately .
analyses of scientific literature connected with influence of preparations from plants of genus panax on physical work capacity is more complicated when compared with that of their influence on cognitive functions .
similar to the situation with memory and attention , most studies are connected with preparations from p. ginseng .
results of many animal experiments attest that p. ginseng preparations can significantly increase physical work capacity .
administration preparations with different qualities from this plant in different dosages increase exhaustion time for swimming in mice [ 55 - 58 ] and rats   and exhaustion time for treadmill running in rats [ 60 - 62 ] . short - term ( 4 d ) , although not acute , treatment with complex of ginseng saponins ( 10 and 20 mg / kg / d ) significantly prolongs the aerobic endurance of non - trained rats exercising at approximately 70% vo2max 
 .
wang et al .   established that pec ( the oral liquid which consists of p. quinquefolius , epimedium brevicornum , s. chinensis bail and cervus eplaphus ) administration could prolong swimming duration of mice in water tank and increase the tolerant ability against oxygen - deficiency . however at the same time , results of some other experimental studies show no significant influence of ginseng on physical work capacity . martinez and staba   established that saponin extracts from different kinds of p. ginseng ( korean red , shiu - chi red , kirin red and sanchi ginseng ) and p. quinquefolius ( canadian , american white and american red ginseng )
ergogenic stems from the greek roots  ergon and  genes, meaning  work and 
any means of enhancing energy production or utilization may be described as an ergogenic aid .
it defines ergogenic aids as substances , foods , or training methods that enhance energy production , in use or recovery , while providing athletes with a competitive advantage .
regarding to herbs currently being used to enhance physical performance , bucci   subscribed that they can have different reasons for use including their adaptogenic properties , testosterone - like ( anabolic ) effect , stimulating effect on central nervous system , effect on capacity to increase endogenous testosterone production ( testosterone booster ) , and alpha - adrenergic agonist properties etc .
a wide understanding of ergogenic aid makes this term a practical definition in the field of sport science and sport medicine but not pharmacology . according to modern pharmacological classification
, p. ginseng and most other herbs from genus panax should be definite adaptogens due to their ability to increase physical work capacity in a healthy person , this being one of the important components of adaptogens action .
however on the other hand , different adaptogens have different capacities to increase physical performance .
that is why adaptogens with the strongest potency to increase physical work capacity are referred to actoprotecors .
according to conventional wisdom , it is reasonable to refer agents from actoprotectors class to synthetic adaptogens and to regard their strong actoprotective effect as one of their components of adaptogenic action .
it should be stressed that the focus of this study is on the ability to enhance physical work capacity and not on the adaptogens origins , synthetic or natural . according to this point of view
, adaptogens of natural origin also can be referred to actoprotectors if they have potent influence on physical work capacity
. some mechanisms of antifatigue action can be included into adaptogen action ; but other mechanisms can be different . as we see regarding to ginseng ,
its actoprotective properties are very discussible , but antifatigue properties have even more evidence supporting this along with proofs . from the results of experimental and human studies on the influence of ginseng preparations on physical performance and restoration after loads , there are many other controversies besides those mentioned about critical points of protocols and experimental techniques , including administration of different quality and composition ginseng supplements .
detail analyses of experimental results demonstrated no influence by ginseng based on the swimming exhaustion time of rats and mice indicating critical points .
for example , in one study some experimental groups included very few animals ( 3 - 4 ) . in this study ,
results of the swimming test generally showed variable swimming time ( 205 - 592 min ) .
it can not be excluded that such various individual results can possibly be connected with methodological defects because of the difficulties in managing swimming test ( water of room temperature was preferred to avoid gas sorption on hair but could not use fresh tap water ) along with insufficient quantity of animals in some experimental groups . in jung
et al.s study , very high doses of ginseng extract were used ( 500 mg / kg / d ) during a long time period ( 4 wk ) , although it is well - known that too high of dose of adaptogens can lead to inverse effects .
results of human studies with plants from genus panax on physical performance ( adapted with modifications from ) # , data not listed or unavailable ; co , crossover ; db , double - blind ; dmae , dimethylaminoethanol ; f , female ; fsh , follicle stimulating hormone ; lh , luteinizing hormone ; m , male ; nc , not controlled ; panas , positive and negative affect schedule ; pc , placebo - controlled ; poms , profile of mood survey ; r , randomized ; rer , respiratory exchange ratio ; rpe , ratings of perceived exertion ; sb , single - blind ; ve , expiratory ventilation .
results from numerous human studies , which are summarized in table 1 , are also controversial . similar to animal experiments ,
( cited in ) demonstrated that ginseng supplementation had no effect but had a very small sample size ( 5 athletes in experimental group and 6 in placebo group ) .
ziemba et al .   established that ginseng administration does improve psychomotor performance during exercise without affecting exercise capacity in their study with soccer players , but used non - specific method for this kind of sport test ( incremental bicycle ergometer exercise test ) .
.   demonstrated substantial ergogenic effects but for ginseng combined with dimethylaminoethanol bitartrate , vitamins , minerals , and trace element .
established that ginseng supplementation does not exert an ergogenic property on aerobic fitness enhancement in well - fit individuals with 60 young men ( 30 in experimental and 30 in control group ) , but used non - standardized 100% ginseng instead of any standardized ginseng preparation such as g115 , products of korea ginseng corporation . or any other standardized extract .
two separate studies forgo et al , 1981 and 1982 respectively ( both cited in ) , showed significant change in aerobic capacity , lactate level , and heart rate under ginseng administration but failed to show either placebo or control conditions .
forgo   did , however , extend these studies with a double blind placebo - controlled investigation into the effects of 9 weeks administration of g115 , g115 plus tocopherol , or placebo , on physiological and hormonal measures ( luteinizing hormone , testosterone , and cortisol ) in athletes .
he reported the significant increase in oxygen uptake and significant decreases in both exercise blood lactates and heart rate , but no change in hormone levels for both of the active treatments in comparison to placebo .
this was followed by a further double blind study investigating the duration of the effects of 9 weeks administration of g115 ( 100 mg twice daily ) during exercise .
results reported a significant increase in oxygen uptake and forced expiratory volume and significant decrease in heart rate and visual reaction times .
some of these differences persisted at 3 weeks at the end of administration of g115 ( forgo and schimert , cited in ) .
liang et al .   reported that 30 d administration of p. notoginseng improves endurance time of exhaustion , and lowers mean blood pressure and vo2 during endurance exercise in healthy untrained adults .
other studies do not support the view on ginseng as supplementation increases physical work capacity .
.   reported that acute p. ginseng supplementation does not affect the endurance of running performance of the heat - adapted male recreational runners in the heat .
morris et al .   found that 1week administration of two different doses of ginseng does not show better effect on any of the physiological indices under investigation ( oxygen , free fatty acids , lactate , and glucose ) than placebo in a placebo - controlled , cross - over study .
allen et al .   reported , in a randomized double - blind , placebo - controlled study involving 28 healthy young adults , that the administration of 200 mg ginseng extract for 21 d did not significantly affect heart rate or perceived exertion at 150 and 200 w ergometric exercise and claimed that it did not affect vo2 , exercise time , workload , plasma lactate , or hematocrit at peak levels of exercise .
did not establish any increasing of physical work capacity after its course administration in a many - years series of ergogenic properties of g115 .
thus , engels and wirth   failed to demonstrate any effect of 8-weeks administration of ginseng on o2 consumption , respiratory exchange ratio , minute ventilation , blood lactic acid levels , heart rate , or perceived effort in a randomized double blind placebo - controlled g115 trial involving 36 healthy men .
engels et al .   found no effect of 400 mg / d g115 for 8 wk on supramaximal exercise performance and postexercise heart rate in 19 healthy women .
engels et al .   failed to demonstrate improvement of physical performance and heart rate recovery of individuals undergoing repeated bouts of exhausting exercise of 8-weeks administration of ginseng ( g115 , 400 mg / d ) in a double - blind , placebo - controlled , randomized study involving 38 active healthy women .
morris et al .   found that no influence of short ( 7 d ) administration of p. quinquefolius water - ethanol extract (
8 or 16 mg / kg / d ) on cycle time to exhaustion and physiologic responses for loads in healthy people .
direct increasing of physical work capacity after acute or course administration ( actoprotective properties ) should be separated from increasing of recovery speed after previous physical or other heavy loads for the convenience of administration of ergogenic aids in practice of sport preparedness as well as for pharmacological study of their mechanism of action .
the property of increasing of recovery speed after previous physical or other heavy loads can be defined as 
drugs and dietary supplements with antifatigue properties are very important in some types of sports with demand for repeated performance after short intervals ( academic rowing , kayak and canoe paddling , different styles of wrestling , etc . ) .
positive influence of p. ginseng on parameters of recovery after exhaustive physical loads has been proved by numerous animal experiments since the 1970 s .
the first article published in 1974   studied the effects of extracts obtained from p. ginseng root ( 50 - 200 mg / kg intraperitoneal , immediately following the exercise ) on recovery from exhaustion ( four hour oscillation movements ) using six methods : exploratory movement ( em ) , hole cross ( hc ) , rotating rod ( rr ) , sliding angle ( sa ) , spring balance ( sb ) and rectal temperature ( rt ) tests .
water extract significantly accelerated the recovery after em , increased motor activity index in em test , and elevated rectal temperature
. however , water extract decreased the index in hc test and grip tone in sb test .
lipophilic fraction significantly sped up the recovery from fatigue in em , rr , rt , and sb tests while delaying recovery in hc and sa tests .
later , banerjee and izquierdo   studied antistress and antifatigue properties of p. ginseng preparation on swiss albino mice which were exposed to various experimental models of stress in comparison with piracetam .
both ginseng and piracetam were administered chronically in drinking water for 16 to 18 d as well as acutely 30 to 60 min prior to the experiments by injection .
reactivity of the mice , loss of body weight , amount of feces , length of endurance , and incidence of mortality were graded and measured .
both piracetam and ginseng treatment provided good protection against electroshock stress when compared to untreated mice . fighting scores , incidence of tonic convulsion , and mortality
were significantly less in the treated groups . in the heat stress experiments , both piracetam and ginseng provided significant protection to the heat - exposed mice . in the fatigue stress of forced swim test ,
ginseng treatment was provided to be effective on adaptation to fatigue and ginseng also increased the endurance in both male and female mice .
piracetam , on the other hand , only showed some antifatigue effects in the male mice . in the locomotor activity tests ,
ginseng did not depress motility , while piracetam did as described in the later part of the tests . from human studies on healthy people and clinical studies on patients who suffered from fatigue , the antifatigue property of p. ginseng preparations can be confirmed .
( cited in ) reported that administration of ginseng extract during 12-weeks improves postexercise recovery .
later , postexercise recovery under ginseng administration was confirmed by ng and ng ( cited in ) , mcnaughton et al .
evaluated the effect of the traditional chinese medicine tongxinluo and ginseng which had a good effect on the excess fatigue rats using metabolomics approach .
a metabolomics study was performed on the excess fatigue rats treated with traditional tongxinluo or ginseng based on ultra - fast liquid chromatography coupled with ion trap - time of flight mass spectrometry .
the plasma metabolic profiling data of the control rats , excess fatigue rats , and excess fatigue rats treated with tongxinluo or ginseng were acquired .
the orthogonal partial least squares analysis was applied for the multivariate statistics , leading to the discovery of important differential metabolites distinguishing the excess fatigue rats treated with tongxinluo or ginseng from the control rats and excess fatigue rats .
the results showed that tryptophan , bile acid , and lysophosphatidylcholine metabolism were disturbed in the excess fatigue rats .
the metabolic pattern including the related metabolic pathways of the rats , after being treated with tongxinluo or ginseng , was adjusted towards the normal state .
clinical studies of p. ginseng administration in treatment of unexplained chronic fatigue of unknown etiology demonstrated as effective in 56% cases ; p. ginseng and p. quinquefolius preparations can be regarded also as perspective compounds to improve cancer - related fatigue . in the last 20 yr of scientific literature ,
has been widely discussed [ 67,97 - 101 ] . based on modern understanding of pharmacology terms and definitions
, it seems logical to concretize this debate by dividing it into two questions :  is p. ginseng an actoprotector  and  is p. ginseng an antifatigue supplementation ?  such division has a principal character and needs separate explanation .
analyses of data from properly controlled studies on p. ginseng preparations ( table 1 ) allow us to make the preliminary conclusion that the controversies related to this study are connected with different doses , duration of courses being used in different studies , and physical condition of subjects who participated in these studies .
enhancement of physical work capacity was only observed in studies when : 1 ) higher doses of ginseng supplementation ( over 200 mg / kg / d of standardized extract ) were used , 2 ) there were longer durations of study ( not less than 8 wk ) , 3 ) had larger subjects number , indicating greater statistical power , and 4 ) subjects were in relatively poor physical condition .
one of the explanations that ginseng supplementation has no positive influence on physical performance was made by ferrando et al . .
in their experiments , the effects of the ginseng extract on various biochemical and hematological parameters in male wistar rats subjected to a treadmill exercise protocol were studied for 12 wk .
the increase was the largest for the animals treated with the extract during the third month of the study .
the exercise alone also led to the increase in these parameters , while the combination of both exercise and ginseng extract produced smaller increase .
this study shows a clear physiological response due to the ginseng extract administration that reproduces many of the effects obtained after long - term exercise .
authors made conclusion that the combination of exercise and treatments seems to support the theory that there is no clear synergic effect when compared with the performance of exercise .
in other work , the same authors established that treatment with p. ginseng increases the capillary density and the mitochondrial content of the red gastrocnemius muscle of rats .
the results suggest that prolonged treatment with p. ginseng increases the capillary density and the oxidative capacity of the muscles with greater aerobic potential in a manner similar to the performance of physical exercise .
this explanation can be accepted as one possibility , but it generally can not be a foundation for the conclusion that any effects of physical training and ginseng supplementation may be obtained separately but not when combined .
the facts mentioned above allow us to conclude that p. ginseng ( and other plants from genus panax , possibly ) can be regarded as a potential actoprotector and antifatigue preparation with further research of its influence on physical work capacity , endurance and restoration after exhaustive physical loads in comparing with reference actoprotector bemitil .
possible biochemical mechanisms for increasing the endurance after ginseng administration are connected with its influence on 1 ) carbohydrate and fat metabolism [ 57,63,104 - 106 ] , 2 ) immune and endocrine mechanisms , and 3 ) regulation of oxidative balance [ 106 - 111 ] .
it seems possible , that in realization of the actoprotective and antifatigue properties of ginseng preparations , saponins are not the only components that have big importance .
wang et al .   established that ginseng polysaccharides have anti - fatigue activity , reflecting in the effects on the physiological markers for fatigue .
it seems logical that such controversies are connected with different doses , duration of courses used in different studies , as well as with administration of different quality and composition of ginseng supplements .
such a conclusion also allows ginseng to be regarded as potential actoprotector and allows for further research on its influence on physical work capacity , endurance and restoration after exhaustive physical loads in being compared to reference actoprotector , bemitil .
numerous animal experiments and clinical studies about the influence of ginseng preparations ( mainly preparations from p. ginseng ) on cognitive functions show less controversial results compared to studies connected with exercise performance .
several of them show memory improvement after ginseng administration . various memory - impairment models ( aged animals , scopolamine - induced memory deficit , ethanol - induced memory deficit , electroconvulsive shock - induced memory disturbances , muscarinic - induced memory deficit , dopamine - induced memory deficit , brain ischemia , cerebral infarct , sham or medial prefrontal cortex lesions , reserpine - induced orofacial dyskinesia , beta - amyloid - induced amnesia model , etc . ) have been used to evaluate the effects of ginseng and its active ingredients on a person s learning and memory .
results of experimental studies on normal animals and on mentioned above animal models are summarized in table 2 .
results of animal experiments with separated ginsenosides and preparations of plants from genus panax on cognitive functions # , data not listed or unavailable ; i.p . , intraperitoneal ; p.o . , per os ; wsf , water - soluble fractions ; lsf , lipid - soluble fractions ; pd , protopanaxadiol ; pt , protopanaxatriol ; pnb , p.
notoginseng burk ; bdnf , brain derivative neurotrophic factor ; pns , p. notoginseng saponins ; samp8 , senescence accelerated mouse prone 8 . in most studies ,
independent of experimental model used , course administration of p. ginseng preparations had as a final result with significant antiamnaestic effect .
in addition , positive results for cognitive functions enhancement were received from preparations of p. quinquefolium 
 , p. notoginseng 
  and p. pseudoginseng 
 . however ,
for example , saito et al .   found that extracts of ginseng inhibits conditioned avoidance response and discrimination behavior on pole climbing and shuttle box tests .
similarly , petkov and mosharrof   found that high doses of g115 impaired , rather than improved , conditioned reflex activity , and takagi et al .   and takagi et al .  
demonstrated decreasing exploratory activity and a specific blocking action of conditioned responses following the administration of a crude ginsenoside fraction .
some experiments were provided with isolated components of ginseng preparations , first with ginsenosides rg1 and rb1 . in passive avoidance test ,
rg1 improved learning and memory acquisition , consolidation , and retrieval , indicating that rg1 can improve all stages of memory .
later , to study the effect of rg1 on one s learning and memory loss induced by -amyloid , passive avoidance and performance in the morris water maze were assayed after the final treatment .
ginsenoside rg1 significantly decreased the latency and swimming distance , improved corresponding changes in search strategies in the morris water maze , and increased the step - through latency .
in other studies , rg1 significantly improved memory deficits in aged rats , ovariectomized rats , and cerebral ischemia - reperfusion rats ( qiu et al .
these results showed that ginseng extract and ginsenosides rg1 and rb1 facilitated acquisition and retrieval of memory .
moreover , ginsenosides rb1 and rg1 also antagonized memory loss and cognitive deficit under various pathological conditions , such as cerebral ischemia and dementia ( qiu et al .
, cited in ) . at the same time , other ginsenosides like rg3(s ) , rg5/rk1 , and rh2   and even nonsapongin fraction of red ginseng   also have antiamnaestic properties and may have some importance on prevention of memory impairment or treatment of memory disorders .
results of most human studies , connected with evaluation of influence of ginseng supplementation on cognitive functions , are summarized in table 3 .
some of these studies show positive effects of ginseng preparations even at acute [ 148 - 150 ] or short course   administration .
poor standardization of different preparations unfortunately does not allow for the comparing of results from different studies .
in this connection , it is necessary to put attention on row of studies provided with g115 [ 152 - 160 ] .
effects of acute administration of g115 on cognition in young healthy individuals were evaluated in randomized double blind placebo - controlled studies [ 152,156 - 158 ] where ginseng differentially improved scores on a  secondary memory factor ( a composite of four memory tasks ) . in the first study ,
secondary memory was found following 400 mg at four post - dose testing sessions while the lower and higher dosage reduced performance on the  speed of attention factor .
secondary memory. a later study assessed the effects of 200 and 400 mg ginseng during sustained cognitive demand - repeated cycles of serial threes , serial sevens , and the bakan rapid visual information processing ( rvip ) task .
serial sevens performance was improved by the 200 mg dose . in a follow - up study ,
it appears that p. ginseng or its constituents are capable of producing tangible cognitive enhancing effects and that 200 to 400 mg appears to be the optimal dose range for young healthy adults when administered acutely prior to a cognitive test .
course administration of ginseng preparations in most studies also showed positive effect on cognitive functions ( table 3 ) .
results of human studies with plants from genus panax on neurocognitive function ( adapted with modifications from ) # , data not listed or unavailable ; co , crossover ; db , double - blind ; dmae , dimethylaminoethanol ; f , female ; fsh , follicle stimulating hormone ; grs , ginseng - rhizome saponin ; lh , luteinizing hormone ; m , male ; nc , not controlled ; panas , positive and negative affect schedule ; pc , placebo - controlled ; poms , profile of mood survey ; r , randomized ; rer , respiratory exchange ratio ; rpe , ratings of perceived exertion ; sb , single - blind ; ve , expiratory ventilation .
detail analyses of mechanisms to determine underlying the positive impact on cognition under ginseng administration is out of the focus of this article .
they are already described in numerous review articles published in recent literature [ 146,156,171 - 180 ] .
it is necessary to subscribe that among these mechanisms is the capacity of ginsenosides to potentiate the cholinergic system in central nervous system .
other important neurotransmitters for learning , memory , and cognitive functions involved in mechanism action of ginsenosides are glutamate   and 5-ht .
similar to studies connected with physical performance , it seems logical that such inconsistencies in the results of different studies are connected with different doses , duration of courses used in different studies , as well as with administration of different quality and composition ginseng supplements . despite that , most studies show positive influences of ginseng supplementation on intellectual work capacity in normal subjects and those of decreased cognitive functions
. such conclusion also allows ginseng to be regarded as potential actoprotector and opens the way for further research of its influence on mental work capacity and cognitive functions in comparing with reference actoprotector , bemitil , and reference nootropic drug , piracetam .
related to the capacity of many plant adaptogens to increase physical and mental performance , the question that arose about actoprotectors class including not just only synthesized but also natural origin compounds has importance for fundamental theory of pharmacological science and practical administration of many phytochemicals .
the ginsenosides content in ginseng preparations can vary depending on the species , the age and part of the plant , the preservation method , the season of harvest , and the extraction method . in this connection ,
poor standardization can cause some difficulties in the evaluation of data received from animal experiments and human studies about the pharmacological activity of adaptogens including ginseng . despite these difficulties , large quantities of data received from animal experiments and human studies allow for making some preliminary conclusions about potential actoprotective properties of ginseng preparations : 1 ) results of some animal experiments and human studies attest that p. ginseng ( administered as extract ) can significantly increase physical and intellectual work capacity and the data allow ginseng to be referred as an actoprotector of natural origin ; 2 ) results related to the influence of ginseng on physical performance are more controversial than those connected with its influence on intellectual work capacity ; and 3 ) ginseng preparations can be regarded as potential actoprotectors and allow for further research of its influence on physical and mental work capacity , endurance , and restoration after exhaustive physical loads in comparing with reference actoprotectors ( bemitil ) and nootropic drugs ( piracetam ) .
pharmacological activity of preparations received from different species from genus panax should be evaluated separately , but extract preparation should be standardized .
comparison of ginseng preparations with preparations of other adaptogenic herbs will allow the decision of the most effective herbal actoprotectors .
composition based on additive effects of herbal actoprotectors and synthesized ones can become the more useful in clinical and preventive medicine .
 actoprotectors are preparations that increase the mental performance and enhance body stability against physical loads without increasing oxygen consumption . 
 actoprotectors are regarded as a subclass of adaptogens that hold a significant capacity to increase physical performance . 
 the focus of this article is studying adaptogen herbs of genus panax ( p. ginseng in particular ) and their capabilities as actoprotectors . some animal experiments and human studies about actoprotective properties of genus panax attest that p. ginseng ( administered as an extract ) significantly increased the physical and intellectual work capacities , and the data provided suggests that ginseng is a natural source of actoprotectors . 
 preparations of ginseng can be regarded as potential actoprotectors which give way to further research of its influence on physical and mental work capacity , endurance and restoration after exhaustive physical loads while compared with reference actoprotectors . 
INTRODUCTION
DEFINITION AND CLASSIFICATION OF ACTOPROTECTORS
COMPOSITION OF GINSENG PREPARATIONS AND THEIR STANDARDIZATION
EFFECT ON EXERCISE PERFORMANCE
EFFECTS OF GINSENG ON COGNITIVE FUNCTIONS
CONCLUSION