Adaptogens, Stress and Cortisol

The stress is a non-specific reaction of an organism to various influences without dependence from their nature. It is known that the majority of pharmacological effects of adaptogens externally manifested as antistressor action (Kirilov, 1966*1). As it is considered that General Adaptation Reaction (GAR) begins with irritating of the peripheral terminals of nervous system, stimulation of a reticular formation, the central nervous system which through a hypothalamus activates secretory function of a forward lobe of a pituitary gland, which is followed by biosynthesis and release of ACTH, which in its turn stimulates the hyper secretion of the steroid hormones by the adrenal glands. It results in their functional hypertrophy. The adrenal cortex releases hormones of two kinds – gluccorticoids and mineralocorticoids. In conditions of stress basically is enlarged the amount of glucocorticoids to which the cortisol (Hydrocortisone) and its analog at rats – Corticosteron belong to. So, where the hormonal rearrangement of an organism in conditions of stress is directed to? Considering that all adaptive hormones (cortisol, catecholamine and insulin) the major factors of physiological regulation or energy metabolism, is possible to tell with confidence that it is directed first of all on its activation.

The leading role in realization of nonspecific reactions of an organism is played by catecholamines and glucocorticoids. The main glucocorticoids in humans is cortisol (Hidrocortizon) and with rats Corticosteron. However they (first of all cortisol), providing the development of a resistance of an organism, also enhance the catabolic processes. Such is the picture of the alarm stage of GAR. The organism cannot exist for a long time in such forced regimen. The mechanisms are turning on that lowering the production and hence the contents in a blood of counter-hormone of cortisol – insulin. Though it is realized the numerous effects in relation to regulatory influence of catecholamins and glucocorticoids in an organism. There come a stage of resistance of GAR.

Concentrations of cortisol in blood in a phase of a resistance can vary depending from the force of stressor and its periodicity (Panin, 1983*2).

In a phase of exhaustion there is a critical depletion of functional reserves, which cannot be compensated by tension of regulatory mechanisms any more therefore falling a level of functioning of adrenal glands is observed. There comes a death of an organism because of infringement of energy supply of adaptation process.

Application of adaptogens substantially modifies the general picture of hormonal rearrangement of an organism in conditions of stress. First of all adaptogens enhance the level of adrenal – glucagons reactions (mobilization of glucose) in a shock phase of alarm stage of GAR the development of which is not enough (Kulagin, 1976*3). At stressor influence after the adrenal glucagons reactions the system hypothalamus-hypophysis-adrenal cortex (HHAC) starts to be activated. Adaptogens influence its activity in various stages of GAR unequally.

During a shock phase GAR concentration of corticosteron (cortisol) under adaptogens grows faster, stimulating, thus development of adaptation process in an organism. This process allows an organism to achieve a counter shock stage of GAR much faster, preserving thus energy deposits of an organism which is in a phase of shock are not spent especially intensively.

Thus, influence of adaptogens on a system HHAC depends on its functional condition. In optimum doses adaptogens do not influence its activity in intact animals. In a shock stage of GAR they accelerate the intact animals. In a shock stage of GAR they accelerate development of stress reactions and in a counter shock stage display antistressor activity due to modulating action of the appropriate hormonal influences.

In a resistance stage, when the increased concentration of glucocorticoids is not so necessary for passing of adaptation processes and provokes predominance of catabolic processes above anabolic, adaptogens reduce their level. Thus they preserve functional reserves of an organism, providing essential extending of duration of a resistance stage. One of the possible mechanisms for reducing of glucocorticoids in blood exists in free and in bound state. Only free steroids cause a biological activity. Corticosteroids bound to protein play a role of reserve and are biologically inactive. So if at stressed animals in comparison with the control the binding activity of transcortin grew up by 50%, administration of an eleutherococcus against a background of stress enlarged those in 4 times. Similar action also rendered the administration of ginseng (Golotin, 1968*5). It is interesting to note that administration of eleutherococcus and ginseng to rats – long livers not subjected to stress, also resulted in sharp elevating of the binding activity of transcortin – 4.5 times and 6 times accordingly. This fact allows making rather exciting assumptions to which we shall return a little bit later. Thus the elevating of the ginding activity of transcortin not only reduces concentration of corticosteroids in blood but also causes building their reserve for use during resistance stage of GAR. It promotes not only extension of its duration but also prevents the dystrophy of adrenal cortex due to decreasing of its hyperactivity.

Thus in a shock phase of GAR (suspension of rats for skin cervical fold for 30 minutes) concentration of corticosteron (analog of human cortisol at rats) in a blood was increased more that in 4 times and under influence of summary glucoside fraction of eleutherococcus against a background of stress in 5 to 6 times.

In conditions of 15-hours stress ( a counter chock stage of GAR) concentration of corticosteron in a blood of control animals was 3 – 5 times higher that at intact animals while at rats administered with the summary of eleutherococcus flycosides in 1,6 times. Therefore the adaptogen rendered anti-alarm action (Dardymov, 1982*4). Similar results have been received in experiments with 24-hours immobilization. The sharp elevation of contents of 17-ketosteroids (17-KS) decomposition product of corticosteron) was marked in urine up to 8 times. Under influence of the summary of eleutherococcus the alarm reaction has been less expressed, and the content of 17-KS in urine has increased only in 4 times.

In experiment with application of stress factor of 15-minute intensive forced swimming with a load on tail, the following results have been received. The stress invoked the rising of concentration of 11-oxycortocosteroids in a blood 4 times. Preliminary administration of the summary fraction of eleutherosides 1 hour prior to swimming prevented such considerable accumulation of 11-oxycortocosteroids, which made 150% from a control level.

In other series of experiments the 15-minute swimming of rats invoked rising the concentration of corticosteron in blood in 2,6 times and decreasing in insulin to level of 54% from the control. Preliminary administration to animals of eleutherococcus extract prevented from the sharp exhibition of stress reaction. Concentration of Corticosteron made 122% level of insulin 61% from control (Dardymov, 1993*6). Ability of adaptogens prevented from the decreasing of insulin level is very important as prevents development of diabetes of tension. In addition to this, according to the modern concept of the biochemical mechanisms of stress the concentrations of corticosteron (cortisol) and insulin are closely interconnected and at a ratio of its concentration expressed in percentage reflects the compensatory abilities of an organism. In intact organism it makes 1. In above mentioned experiment with swimming in a group of animals subjected to stress it made 4.7 and in conditions of swimming against on a background of eleutherococcus administration – 2 i.e. came nearer to normal.

Thus adaptogens render a stress protective activity in a counter shock phase of the alarm stage of GAR with decrease of changes of catabolic nature in metabolism.

Coming back to the data on increasing of transcortin in binding activity under action of adaptogens at rats long-livers, it is possible to assume that this phenomenon can be one of factors of adaptogens determine the ability to enlarge lifetime of animals up to 10% (Golotin, 1972 *7). It is known that with the years in an organism the concentration of cortisol that reflect a level of cumulative stress during vital activity in enlarged. An important role during aging plays the activization of transcortin binding activity is capable to transfer the cortisol to the bound inactive form, reducing thus negative consequences of its catabolic activity.

ADAPTOGENS - OR WHAT WE CAN PUT ON THE WAY OF STRESS.

The stress is the major problem on the Earth. All are subject to stress - from neonatal up to the ailing old man.

Some consider that the person in the modern world is in less stressful situation, than the person of past epoch. Rather on the contrary. It is impossible to argue with the Selye, that the fear and trembling of the primitive hunter before a predator invoked the same stressful reaction, as well as fear of the modern employee before the terrible chief. Endocrine - biochemical alterations probably similar, but in the second case is absent an opportunity for merely physical relaxation (an offence, escape behavior), emotions are not discharged, and it is necessary to suppress them. The primitive person had less rich imagination (he was not skilful “to make mountains out of a molehill”); he touched much less variants possible, particularly remote, consequences of a dangerous situation, reducing probability of development of a mental stress. According to the modern data four from five adults suffer from any form of a strain and alarm. Despite of all modern conveniences making our life “easier”, we taste in one day more stress, than our primitive ancestors in month or year. Except that, technical progress results in formation of principally new stressful factors, such as radiation, products of the chemical synthesis, the modified forms of causative organisms, toxic byproducts, environmental pollution etc. One of latest and thus the most dangerous on its consequences for broad masses of the population the stressful factor is the international terrorism. Acts of exhibiting, which invoke deep depression in a society, down stroke of creative and vital potential of the most productive, highly educated and consequently most vulnerable part of the population.

On a question about if it was possible to live without stress? Only the negative answer follows. To live without stress is impossible and even harmful. The question is different: How to live in conditions of stress? According to Selye it means to provide to itself a “stress without distress” (such Selye has entitled one of his last books (1); a distress - harmful, unpleasant stress). For achievement of this purpose the Selye offers correctly estimate a situation and to switch on one (cattotoxic) or another (syntoxic) group of hormones. The first - for “fight”, for “war”, the second - for complacency. Selye considers that we too roughly react on that, actually does not demand such reaction. That the person itself should define for himself an optimum level of a stress. How to achieve it? The founder of the doctrine about a stress correctly recommends to estimate the forces and not to try to solve a problem which is higher than opportunities of the given person.

Well and what in general has saved up experience of mankind what may be put against stress? Let's review the active methods of rising of the general resistance (ability to resist to factors of external influence) of organism. They can be divided into three groups.
The first group includes the methods using physical factors of influence. It is physical training, physical conditioning, an acupuncture, staying of people in conditions of a mid-land. The second group: autogenic training, psychotherapy, hypnosis. And the last, third group of methods of rising of a resistance of an organism is related to application of the biologically active substances. Professor Brekhman I.I. called it -pharmacosanation.

From all possible methods and agents of adaptation people have preferred biologically active substances.

Huge amounts of biologically active substances get into an organism with nutrition, wine, soft drinks and medicinal preparations.

Undoubtedly, that the diverse vegetative nutrition plays the important role in modern conditions of human life. It brings up in an organism not only a limited set of vitamins, but also the much greater number of the diversified biologically active substances. People from ancient times understood and appreciated useful influence of these fetuses of the ground and sun. It is possible to believe, that reduction of this one part of nutrition is seriously reflected in a state of health of people and their resistance to a stress.

Avicenna and other adherents of Oriental medicine widely used “medicinal nutrition”, or “alimentary medicine” which was separate plants acted or more often their complex mixtures. Among medicinal plants of Oriental medicine of some countries food plants make about half.
Stress protection – is a decision of peculiar engineering problem. As for example there are mechanisms that may work in conditions of high temperature and humidity, and in our case there is a person who is necessary for making steady against a stress. He should pass through stressful influence and remain alive minimally damaged, kept the capacity for acting.

Agents are necessary which would raise body resistance to stresses and would not decrease thus its work capacity.

The specified purpose may be achieved only by optimization of the physiological processes inherent to the organism providing a natural general nonspecific resistance. This way has been chosen by professor N.V.Lazarev, which has offered together with professor M.A.Roziny the new remedy - Dibazolum, and named new group of medicinal substances - adaptogens. Further the doctrine about adaptogens has received development in works of Great Russian scientific and my teacher, professor I.I.Brehman. The big role in formation of the group of remedies characterizing as adaptogens has played the Eleutherococcus.

So, what are adaptogens? Adaptogens - a new class of biologically active agents, basically of the connatural parentage, creating in an organism a state of the nonspecific raised resistance, and at long consuming rising of adaptable abilities of an organism. As was already mentioned earlier, the state of the nonspecific raised resistance arises at muscle trainings and has some similarity to a stage of a resistance of the general adaptation reaction, though is not completely identical to it.

Numerous experiments with Eleutherococcus, one of the most investigated and popular adaptogens have shown that it is a pharmacological agent which relaxes the manifestations of stress and simultaneously enlarges resistance and durability of an organism.

This property of an Eleutherococcus was repeatedly confirmed in observations in studies with volunteers. In long sea voyage the Eleutherococcus has lifted body resistance of rank-and-file members of crew up to a level of the qualified sportsmen (2) which tolerated tropical conditions more easily. Other well-known adaptogen - the leusea carthamoides was successfully used for improving a function state of nervous system, augmentation of mental and physical efficiency at sailors in conditions of long Arctic navigation (3). Preventive action of an Eleutherococcus successfully utilized for downstroke of a sickness rate among workers on chemical production (4) and other production enterprises, and also workers of agriculture (5). The most numerous (up to 60 000 workers) was study on Volzhsk automobile factory in Tolyatti where the sickness rate an influenza has decreased on 30-35 %, and work-losses - on 20-30 %. Rather convincing is the study which have been carried out with the truck drivers which received with tea (in voyages they took thermoses with the same tea) daily a 0, 25 ml of Eleutherococcus extract within 2 months. Such courses of prophylaxis carried out 2-3 times per one year within 6 years. Such application of an Eleutherococcus reduced the sickness rate with influenza and other illnesses, such as an ischemia and a hypertonia (6) few times.

Whereas adaptogens use the steady popularity, many explorers and the commercial companies frequently hasty rank as adaptogens mass of new drugs, those not is being. With sufficient confidence it is possible to attribute to adaptogens only some agents: preparations of a ginseng (Panax ginseng C.F.Mey), Eleutherococcus (Eleutherococcus senticosus Maxim.) (7; 8; 9), leusea (Leuzea carthamoides DC.), rhoddiola (Rhodiola Rosea L.) (10), echinopanax (Echinopanax elatum Nakai), aralias mandzhurica (Aralia mandshurica) (11), acantopanax (Acantopanax sessiliflorum), schizandra (Schizandra chinensis) (12), Pantocrinum and rantarin. At present, in connection with the big scope of scientific data obtained we can attribute to a class of adaptogens the Olygomeric Proanthocyanidin complexes (13), possessing the necessary set of biological activities (14). Considering, the fact, that olygomeric proanthocyanidins represent the basic part of a polyphenolic complex of a grapes, wine, apple and cider, its consuming by the humans counts already more than 6000 years (15.) such age has viniculture and winemaking (16). All this allows us to express the statement about evolutionary adaptedness of an organism of the human for perception of these biologically active substances (13) which is proved by numerous studies of pharmacological activity of this group of substances.

The listed preparations, not looking on some differences in properties, nevertheless have much in common on the basic “adaptogenic” properties. They are “Generators of Adaptation”. They have a wide spectrum of protective activity against numerous unfavorable factors. They raise fastness of animals to an overheating and a frigorism, to the raised muscular load and to a hypokinesia, to a centrifugal acceleration and to a hypoxia, have a protective action to toxic influence of various chemicals and too many infection contaminations, and stimulate detoxication function of a liver.

On a normal background adaptogens have rather modest promoting effect. Their basic property - to recover, restore physiological functions, including ones during the activity. In difference from stimulators of Phenaminum class, which effect is carried out as a result of the “exhaustive mobilization” of energy resources invoking subsequently long droop of function activity, adaptogens do not render such “squeezing out” effect.

Demands to which there should conform an adaptogen were formulated by professor I.I.Brehman (8):

This definition of properties of adaptogens is made more than 20 years back. The basic sense of requirements to adaptogens were kept and until now, but appeared new facts demand addition of corrective amendments. To the perfect harmlessness of adaptogens it is necessary to add - in optimal doses. Functionally changed background is the basic condition of exhibiting of a biological effect of an adaptogen. However this “condition” does not work at chronic disease in result of steadfastly generated new pathogenetic relations, becoming normal for the given organism. For exhibiting of adaptogenic effect of it is necessary some “shakeup” of stress origin, for example surgery.

Thus, essence of action of adaptogens in rendering finally a positive effect on a function shape of an organism, without dependence from a direction of function alteration, optimizing physiological processes inherent to the organism, providing augmentation of a natural general nonspecific resistance.

Referenced Literature...

ADAPTOGENS AND ATHLETES (ADAPTOGENS IN SPORTS)

One of the most important results of the biological properties of adaptogens is the effective application for people exposed to high physical and nervous loading, i.e., for athletes.

It is well known, that muscular activity and nervous loading causes the reaction of stress or stress-reaction that is prevented by usage of adaptogens and, in particular, eleutherococcus.

In order to understand the mechanics of stress-reaction decreasing under the influence of adaptogens, it is necessary to understand the process of activation of the adrenal cortex during stress. General adaptation reaction (GAR) begins with excitation of the peripheral terminal of the nervous system, which through the hypothalamus gland activates a secretory function of the frontal lobe of hypophysis. A synthesis and "release" of adrenocrticotropic hormone (ACTH) follows, which in turn stimulates secretion of cortciosteroids (including cortisol) by the adrenal cortex. An increased state of stress is supported not only by former stress factors, but also by the internal bodily conditions, which have changed as a result of stress, such as the surplus of cortciosteroids that has already become a toxic factor.

Adaptogens thus adjust the metabolic processes in tissue in such a way, that intervention of adaptive hormones becomes less necessary. By the principle of a feedback, the level of activity of the hypophysis - adrenal system is reduced, which results in keeping an optimum level of stability within an organism.

It has been proven that the level of energy expended necessary for an organisim to survive when going from a condition of full rest up to intensive muscular loading can vary ten times. We can present to you that, within this wide range of muscular loading, all physiological functions will be provided without inclusion of stress reactions taking place. This is due to the balanced power inputs. Such condition is referred to as physiological adaptation (in sports the equivalent of a training degree) when the body is adapted (is trained) to adequate conditions of environment and to adequate muscular loadings. Depending on the person’s degree of training, one person walking fast can be provided with energy, without activation of the adrenal cortex, whereas sitting will cause stress in another.

In conditions of the loading exceeding a level of physiological adaptation, i.e. in conditions of offensive stress, additional protective reactions of general adaptable syndrome (GAS) are executed, which can increase the stability of the body many times over. Increase in stability by initialization of GAR is provided due to mobilization of internal resources and cannot proceed for a long time. Further, the resources of an organism spent during stress, are restored. Thus, there is not simply restoration up to a former level but super-restoration. Sports training schedules are based on this phenomenon. The optimum mode provides that the beginning of the next training coincides with the peak of super-restoration, and only then it is possible to expect fast escalation of sports results, i.e. increase in the level of physiological adaptation. If sports training occurs too often, while the obdy has not yet compensated for former expenditures, there is a decrease in the level of physiological (the phenomenon of overtraining). With infrequent trainings, the level of physiological adaptation is not increased, and remains the same.

Similar processes occur to all organisms, which exist nature. Daily small, and average stressful influences cause time prevalence of catabolic processes, replacing at rest by anabolic ones, thus the habitual homeostasis is restored and there is an increase of a level of physiological adaptation takes place. Action of adaptogens besides regulating influence on metabolic processes is connected to creation in an organism a condition equivalent to alternation of the periods of easy stress that results in acceleration of process of adaptation and increase in its physiological level, i.e. training. The synergetic action of adaptogens and the training process results in an accelerated increase of reserve opportunities for the organism. Increasing the level of physiological adaptation provides much stability to an organism against external indignations and loadings at his greater energetic efficiency.

Therefore application of adaptogens in general and in sports in particular, is connected mainly to the fast increase in the level of physiological adaptation (level of a training) due to acceleration of the slowest enzymatic reactions in the anabolic (regenerative) processes and thus an increase in energy and plastic maintenance of specific protective systems. Therefore, improvement of functional maintenance activity of tissue with the help of adaptogens results in an increase in the level of physiological adaptation and makes unnecessary the stress-reaction - it is switched off by the principle of feedback.

Nonspecific resistance is energetically provided in two opposite ways: first, due to increase in the level of physiological adaptation (increase in capacity of key enzymes systems, providing glycolysis and aerobic oxidizing reactions); second, due to a glycogenolysis (use of the glycogen being the form of storage of carbohydrates in an organism) and a glyconeogenesis (formation of glucose not from carbohydrate precursors), mobilized by stress. Application of adaptogens for athletes, on the one hand promotes faster increase in the level of training, due to the more effective utilization of energy resources of an organism and to their faster restoration after trainings. On the other hand, adaptogens diminish the force of stressful influence in the case of muscle loadings that exceed a level of physiological adaptation, due to activation of processes of a glyconeogenesis and a glycogenesis (formation of a glycogen).

High efficiency of application of adaptogens during trainings and directly before competition is confirmed in a number of experimental studies.

In studying the influence of extracts of roots and leaves of eleutherococcus on the work capacity of athletes at static and dynamic loadings, it has been shown that wrestlers, weight-lifters and gymnasts receiving eleutherococcus leaves extract one time and receiving a mix of extracts of roots and leaves by gymnasts in the amount of 2 ml caused an increase in work capacity at static loading (keeping of a corner in thrust) on 6-8 %. In dynamic loading of the maximal capacity (30-second workout on a bicycle ergometer) for gymnasts, who took the mixture of extracts of roots and leaves, resulted in an increase in working capacity by 12% (Blokhin 1966).

In the other studies the influence of the extract of eleutherococcus on the functional condition of cardiovascular system and working capacity of skiers (Dalinger 1966) was estimated. It appeared that an extract of an eleutherococcus in a dose of 4 ml 1-1, five hours prior to start not only reduced the timing of 30 km distance passage by 3%, but also reduced the time of restoration of reference values of pulse and arterial blood pressure by twice as much.

In conditions of a multi-day ski campaign (the group was without special preliminary preparation), all athletes receiving an extract of eleutherococcus, did not show fatigue. Restoration of pulse and arterial pressure occurred twice faster for them in comparison with a control group. All parameters came back to initial parameters by the end of the first day (weight, pulse, arterial pressure). For the control group of skiers, normalization of these parameters in most cases required three days.

Reflection of strong restoration action of the extract eleutherococcus is its influence on muscular tone. After receiving a preparation, the heavy muscular work was carried out easier, and the residual muscular tone has been expressed much more poorly. A day later the muscular tone in the group of skiers receiving eleutherococcus was lowered below initial parameters that reflected more active processes of restoration after the high physical loadings. Under action of an eleutherococcus increase of stability in oxygen insufficiency, and faster restoration of an oxygenation of blood on a dosed out and maximal delay of breath have been marked also. Thus the maximal delay of breath was the longer in duration in skilled group.

Positive influence of a powder of schizandra seeds in the amount of 0.5 g within 20 days resulted in an increase in work capacity of basketball players (Levchenko 1971). Reduction in the duration of normalization of the pulse rate was marked during intensive physical loadings.

Very impressive results were obtained during a 36-day training of swimmers with the influence of saponins from aralia mandzhurica (saparal) in a dose of 50 mg day on processes of restoration of functional parameters. (Sokolv, Monogarov et al. 1971). A wide spectrum of parameters were measured with the athletes, including the functioning of the respiratory system, the cellular blood count, and the functioning of the adrenal cortex, etc.

It is revealed, that the saparal causes reduction in the level of tissue hypoxia after physical loading due to an increase in the oxidation-reduction processes in tissue, promotes strengthening of protective properties of an organism, raising cytophagous activity of leukocytes. After receiving saparal, a more economical reaction of the body occurs in regard to the cardiovascular system and to other parameters. Smaller decrease in work capacity during the first two-three days after the high physical loadings was also evident.

In more detailed studies of the influence of the extract eleutherococcus on athletes (Badul and Badul 2000), swimmers in an experimental group received 2 ml of the extract eleutherococcus daily for 21 days. The experiment showed that Eleutherococcus improved performance essentially in the 50 and 200 m (by 7.6 % and 3.6% respectively). Thus, even after the termination of the dosage of eleutheroccoccus, the experimental group still had steady tendency to improvement of results for two weeks; whereas, productivity of swimmers in the control group tended to fall down. With swimmers in an experimental rate of restoration of pulse after heats has essentially increased, and its frequency right after a heat was stably lower. For swimmers in a skilled group, the improvement of parameters of a spirometry was noted (up to 23 % and carpal dynamometry was noted (up to 5.7 %), _________work of cardiovascular system.

One of factors (benefits?) of action of adaptogens is their action on the cardiovascular system through modulation of the mechanism of curtailing (slowing or thinning?) blood and the formation of nitrogen oxide. A 20-day course of receiving extracts of eleutherococcus and leusea reduced the coagulation potential of blood and activity of factors of curtailing, which grew in conditions of intensive trainings at athletes (Azizov 1997). The extract of a schizandra resulted in an increase in the contents of an nitrogen oxide in the saliva of the athletes and plasma of blood. This is a testament to the ability of adaptogens to promote relaxation of the vascular wall through formation of nitrogen oxide (Panossian, Oganessian et al. 1999).

Thus application of adaptogens by athletes in all cases promotes the accelerated training process or increase in a level of physiological adaptation, and the steady effect of an after-action is marked.

Referenced Literature List