ArticlePDF AvailableLiterature Review

Stimulating effect of adaptogens: An overview with particular reference to their efficacy following single dose administration

October 2005
Phytotherapy Research 19(10):819-38

DOI:10.1002/ptr.1751

Source
PubMed

Authors:

Alexander George Panossian

Phytomed AB

Hildebert Wagner

Ludwig-Maximilians-Universität in Munich

Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors. The beneficial effects of multi-dose administration of adaptogens are mainly associated with the hypothalamic-pituitary-adrenal (HPA) axis, a part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation. In contrast, the single dose application of adaptogens is important in situations that require a rapid response to tension or to a stressful situation. In this case, the effects of the adaptogens are associated with another part of the stress-system, namely, the sympatho-adrenal-system (SAS), that provides a rapid response mechanism mainly to control the acute reaction of the organism to a stressor. This review focuses primarily on the SAS-mediated stimulating effects of single doses of adaptogens derived from Rhodiola rosea, Schizandra chinensis and Eleutherococcus senticosus. The use of these drugs typically generates no side effects, unlike traditional stimulants that possess addiction, tolerance and abuse potential, produce a negative effect on sleep structure, and cause rebound hypersomnolence or 'come down' effects. Furthermore, single administration of these adaptogens effectively increases mental performance and physical working capacity in humans. R. rosea is the most active of the three plant adaptogens producing, within 30 min of administration, a stimulating effect that continues for at least 4-6 h. The active principles of the three plants that exhibit single dose stimulating effects are glycosides of phenylpropane- and phenylethane-based phenolic compounds such as salidroside, rosavin, syringin and triandrin, the latter being the most active.

Results of human studies involving single dose effects of plant adaptogens on physical and mental performance

Figures - uploaded by Alexander George Panossian

Content may be subject to copyright.

Content uploaded by Alexander George Panossian

Content may be subject to copyright.

STIMULATING EFFECT OF ADAPTOGENS 819

PHYTOTHERAPY RESEARCH

Phytother. Res. 19, 819– 838 (2005)

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ptr.1751

REVIEW ARTICLE

Stimulating Effect of Adaptogens: An Overview

with Particular Reference to their Efﬁcacy

following Single Dose Administration

A. Panossian1* and H. Wagner2

1Swedish Herbal Institute, Viktor Rydbergsgatan 10, SE-411 32, Gothenburg, Sweden

2Centre of Pharma-Research, Pharmaceutical Biology, Butenandtstr. 5, University of Munich, D-81377 Munich, Germany

Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors

and to avoid damage from such factors. The beneﬁcial effects of multi-dose administration of adaptogens are

mainly associated with the hypothalamic–pituitary–adrenal (HPA) axis, a part of the stress-system that is

believed to play a primary role in the reactions of the body to repeated stress and adaptation. In contrast, the

single dose application of adaptogens is important in situations that require a rapid response to tension or to

a stressful situation. In this case, the effects of the adaptogens are associated with another part of the stress-

system, namely, the sympatho–adrenal-system (SAS), that provides a rapid response mechanism mainly to

control the acute reaction of the organism to a stressor. This review focuses primarily on the SAS-mediated

stimulating effects of single doses of adaptogens derived from Rhodiola rosea, Schizandra chinensis and

Eleutherococcus senticosus. The use of these drugs typically generates no side effects, unlike traditional

stimulants that possess addiction, tolerance and abuse potential, produce a negative effect on sleep structure,

and cause rebound hypersomnolence or ‘come down’ effects. Furthermore, single administration of these

adaptogens effectively increases mental performance and physical working capacity in humans. R. rosea is the

most active of the three plant adaptogens producing, within 30 min of administration, a stimulating effect that

continues for at least 4– 6 h. The active principles of the three plants that exhibit single dose stimulating effects

are glycosides of phenylpropane- and phenylethane-based phenolic compounds such as salidroside, rosavin,

Keywords: adaptogens; stimulating effect; single dose effect; clinical trials.

Received 13 June 2005

Accepted 20 September 2005

* Correspondence to: Professor A. Panossian, Swedish Herbal Institute,

Viktor Rydbergsgatan 10, SE-411 32, Gothenburg, Sweden.

E-mail: ap@shi.se

INTRODUCTION

Sensory adaptation is deﬁned as the change in the

excitability of a sense organ during continuous stimula-

tion, the result of which is that increasingly intense

stimuli are required to produce the same response.

Physiological adaptation is deﬁned as a biochemical

change in an organism that results from exposure

to certain environmental conditions or stressors and

generates a more effective response to them. Such

adaptive changes convey the organism from its normal

steady state (homeostasis) to a heightened level of

dynamic equilibrium (heterostasis) or to the so-called

state of non-speciﬁc resistance (SNSR) (Lasarev, 1962;

Brekhman and Dardymov, 1968) of the stress system

(a function of the neuroendocrine-immune complex)

(Chrousos and Gold, 1992). The general adaptation

syndrome has three stages: the alarm reaction, being

the point at which the body detects the external

stimulus; adaptation, during which the body engages

defensive countermeasures against the stressor; and

exhaustion, where the body begins to run out of

defences (Selye, 1950). Stress, including both eustress

820 A. PANOSSIAN AND H. WAGNER

and distress (roughly meaning challenge and overload,

respectively), may be the result of negative or positive

events. Whilst eustress is essential to life (in the sense,

for example, that exercise is required to avoid muscular

atrophy), distress can cause disease. Eustress, however,

raises the levels of adrenaline and prostaglandins in the

body, which in turn increases the heart-rate, respira-

tion and blood pressure and places greater physical

stress on the body organs. Long-term stress can induce

heart disease, high blood pressure, strokes and other

illnesses (Chrousos et al., 1995; Fink, 2000).

In the mid 1900s it was suggested that SNSR could

be achieved either by gradually training the organism

to withstand the effect of the stressor, or by application

of biological response modiﬁers, i.e. chemicals that could

directly raise the organism to a state of heterostasis.

Such pharmacologically active compounds were given

the name ‘adaptogens’ (Lasarev, 1962). As originally

deﬁned, an adaptogen was a substance that: (a) showed

some non-speciﬁc effect, such as increasing bodily

resistance to physically, chemically or biologically

noxious agents or factors; (b) had a normalizing

inﬂuence on a pathological state, independent of the

nature of that state; and (c) was innocuous and did not

disturb body functions at a normal level (Brekhman

and Dardymov, 1968). More recently, plant adaptogens

have been deﬁned as compounds that increase the

ability of an organism to adapt to environmental

factors and to avoid damage from such factors

(Panossian et al., 1999a).

The repeated administration of adaptogens gives

rise to an adaptogenic, or stress-protective, effect in

a manner analogous to that produced by repeated

physical exercise, leading to prolonged SNSR and

increased endurance and stamina under extreme

conditions (Dardymov, 1976; Lupandin and Lapajev,

1981; Viru, 1981; Saratikov and Krasnov, 2004). Such

repeat doses of adaptogens have been shown to be of

particular value in sports medicine in which the anti-

fatigue effect can lead, for example, to the increased

endurance of long distance runners during competition

or to a more rapid recovery from a strenuous event

(Korolevich and Lupandin, 1967; Levchenko, 1971;

Lapajev, 1982; Lupandin, 1990; Bucci, 2000).

A characteristic feature of adaptogens is that they

act as eustressors or challengers (Panossian et al., 1999b).

Thus, a single administration of an adaptogen mainly

produces a challenging (stimulating or stress-agonizing)

effect (Nörr, 1993; Panossian et al., 1999b, c; ESCOP

Monographs, 2003a, b), a fact that is used in sports

medicine where a single dose of adaptogen can increase

the performance of sprinters by making them more alert

(Astanin et al., 1943; Murtazin, 1946; Dalinger, 1966;

Tuzov, 1968). It follows that the stress-protective effect

achieved by multiple administration of adaptogens

is not the result of inhibition of the stress response of

an organism, but actually of adaptive changes in the

organism as a response to the repeated stress-agonistic

effect of the drug. In other words, using pharmacological

terminology, adaptogens are stress-agonists and not

stress-antagonists (Panossian et al., 1999c).

The beneﬁcial effect of repeated treatment with

adaptogens is mainly evident in patients suffering

from chronic disease or a disturbed state (Krasik et al.,

1970a, b; Lebedev, 1971; Lapajev, 1978; Lupandin and

Lapajev, 1981; Mikhailova, 1983; Panossian et al., 1997;

ESCOP Monographs, 2003a, b; Saratikov and Krasnov,

2004). Such effects are mainly associated with the

hypothalamic–pituitary–adrenal (HPA) axis, a part of

the stress system that is believed to play a primary role

in the reactions of the body to repeated stress and

to adaptation by balancing the releases of adrenaline

(the ‘switch-on’ hormone), corticosteroids (the feed-

back regulatory ‘switch-off’ hormones that protect an

organism from overreaction), and nitric oxide (that

modulates the biosynthesis and effects of many hor-

mones and autacoids, and plays a role in the nervous,

cardiovascular, immune, gastrointestinal and endocrine

systems).

In contrast, the application of adaptogens in a single

dose is important in situations that require a rapid

response to strain or to a stressful situation. In such

cases, the effects are associated with another part of

the stress-system, namely, the sympatho–adrenal-

system (SAS). This system provides a rapid response

mechanism that mainly controls the acute response of

the organism to a stressor, resulting in increased levels

of catecholamines, neuropeptides, ATP, nitric oxide and

eicosanoids. The present review will focus primarily on

the characteristic SAS-stimulating effects of the plant

adaptogens.

THE STIMULATING EFFECT OF

ADAPTOGENS

The earliest studies of adaptogens (see Table 1) were

concerned primarily with demonstrating their ability to

increase the mental and physical working capacity in

humans (Medvedev, 1963; Dalinger, 1966; Tuzov, 1968)

and in animals following administration of single or

repeated doses (Lebedev, 1971; Lapajev, 1978; Lupandin

and Lapajev, 1981; Panossian et al., 1997; ESCOP

Monographs, 2003a, b; Saratikov and Krasnov, 2004).

It soon became clear, however, that there were very

important differences between the stimulating effects

of adaptogens and those of other stimulants of the CNS

and these are summarized in Table 2 (Fulder, 1980).

Stimulants, deﬁned as drugs that increase the activity

of the sympathetic nervous system, produce a sense of

euphoria and can be used to increase alertness and the

ability to concentrate on mental tasks. Stimulants such

as caffeine, nicotine, amphetamines and cocaine, are

also used, and sometimes abused, to boost endurance

and productivity. However, long-term stimulant abuse

can impair mental function and lead to psychotic symp-

toms. Furthermore, traditional stimulants that possess

addiction, tolerance and abuse potential, produce a

negative effect on sleep structure, and cause rebound

hypersomnolence or ‘come down’ effects. By deﬁnition,

plant adaptogens do not exhibit such negative effects:

in fact one plant adaptogen, that derived from Rhodiola

rosea, has been shown signiﬁcantly to regulate high-

altitude sleep disorders and to improve sleep quality

(Ha et al., 2002).

Plant adaptogens stimulate the nervous system

by mechanisms that are totally different from those

of traditional stimulants, being associated rather with

metabolic regulation of various elements of the stress-

system and modulation of stimulus-response coupling

(Petkov, 1978; Bombardelli et al., 1980; Hasan Samira

STIMULATING EFFECT OF ADAPTOGENS 821

Table 1. Results of human studies involving single dose effects of plant adaptogens on physical and mental performance

Reference to

study

Aksenova

et al.

, 1968

Andrejev and

Georgijev, 1958

Astanin

et al.

1943

Berdyshev, 1995

Study

design

PC, SB

C, CO

PC, CO

Number of

subjects in

the study (

)

357 sailors

Age range

of subjects

20–28

Daily dose

2.5 mg

25 drops

2mL

0.25, 0.5,

1.0, 2.0,

4.0 and

8.0 mL

Type of preparation

tested

Salidroside

Schizandra chinensis

fruits 70% tincture, 1:3

S. chinensis

tincture,

phenamine, caffeine,

48% ethanol

Eleutherococcus

senticosus

extract

S. chinensis

extract

Duration

of study

Acute

Classiﬁcation of

evidence level

according to

WHO, FDA

and EMEA

IIa

III

IIb

IIa

Effects recorded

Improved mental performance; reduced the

number of errors in Anﬁmov’s correction test;

stimulating effect lasting 4 h or more

Increased muscular working capacity

Improved running time in 60% of athletes

E. senticosus

improved mental performance

in correction test; increased activity of the

adrenal cortex (excretion of 17-ketosteroids in

the urine), the activity of the sympathetic

adrenomedullar system (in orthostatic test),

the intensity of metabolic processes (excretion

of vitamin C in the urine), and the intensity

of red-ox processes. In stress conditions

E. senticosus

decreased adrenal cortex activity

and sympathetic nervous system; increased

the tonus of the parasympathetic nervous

system; moderately intensiﬁed excitation of

the CNS and of energy metabolism; improved

endurance to hypoxia

S. chinensis

stimulated the activity of the

CNS at night (activated excitation processes

and normalized nervous processes ratio);

increased tonus of the sympathetic part of the

autonomic nervous system (having no effect

on the parasympathetic part) after night duty;

activated the adrenal cortex activity;

increased the activity of the cardiovascular

and respiratory systems; intensiﬁed

oxidation-reduction and metabolic processes;

improved working ability parameters;

reduced parameters of non-speciﬁc resistance

the organism

822 A. PANOSSIAN AND H. WAGNER

Table 1. (continued)

Reference to

study

Study

design

Number of

subjects in

the study (

)

Age range

of subjects Daily dose

Type of preparation

tested

Duration

of study

Classiﬁcation of

evidence level

according to

WHO, FDA

and EMEA

Effects recorded

Bogatova and

Malozemov, 1994

Bogatova

et al.

, 1997

Dalinger, 1966

De Bock

et al.

, 2004

Eglit

et al.

, 1965

Galochkina, 1948

5 cosmonauts

76 skiers at

four levels

of training

28 athletes

PC, CO,

PC, DB,

R, PC,

DB, CO

Open

study

20–25

19–22

3 capsules

4mL

2 capsules

2, 5, 10 and

15 mL

1.6 g

ADAPT-232, ﬁxed

combination of

standardized extracts

Rhodiola rosea

(salidroside 3 mg),

E. senticosus

(syringin

3 mg),

S. chinensis

(schizandrin 4 mg),

in capsules

ADAPT-232, ﬁxed

combination of

standardized extracts of

R. rosea

E. senticosus

S. chinensis

, in capsules

E. senticosus

tincture

Standardized extract

R. rosea

, 100 mg

in capsule

S. chinensis

seed

20% tincture

S. chinensis

fruit

powder

Compared with placebo, ADAPT-232

signiﬁcantly increased short-term memory,

speed and reliability in the understanding of

information, and precision and accuracy in

the ability to reproduce the information in

repeated highly sophisticated computer-based

tests (Monotonic 2). ADAPT-232 was most

effective against a background of pronounced

fatigue induced by monotonous night work.

The effect was most pronounced in

complicated tests and under

extreme conditions

ADAPT-232 signiﬁcantly decreased the number

of mistakes (

cf.

with placebo) in complicated

psychometric tests 4 h after administration

and increased working capacity 1.5 and 4 h

after administration to Russian cosmonauts

during their training in prolonged isolation

(90 days) under conditions of long-term,

monotonous work. No signiﬁcant effect was

observed in non-complicated tests

Single dose increased working capacity,

shortened recovery period in prolonged

physical load and at low temperatures

Acute intake of

R. rosea

improved endurance

exercise capacity but showed no effect after

daily intake over a 4-week period

Improved the function of the respiratory and

cardio-vascular systems, increased muscle

power of the hand muscles; reduced the time

required by athletes to complete the course

Best results were obtained with doses of 5

and 10 mL

Improved eye retina sensitivity to red

25–30 min after administration

Acute

Acute,

40 min

or 1.5 h

before a

competition

Acute and

for 4 weeks

Acute

IIa

IIb

III

STIMULATING EFFECT OF ADAPTOGENS 823

Table 1. (continued)

Reference to

study

Study

design

Number of

subjects in

the study (

)

Age range

of subjects Daily dose

Type of preparation

tested

Duration

of study

Classiﬁcation of

evidence level

according to

WHO, FDA

and EMEA

Effects recorded

200

sailors

80 healthy

students

(control

group) and

70 patients

with neurosis

8 males

122 students

? students

PC, SB

CO, PC,

20–50

20–22

2mL

200 mL

10 drops

or 3 × 10

drops a day

40 drops

or 3 × 10

drops a day

30 mL

2mL

3 capsules

S. chinensis

tincture

E. senticosus

tincture

Black tea Coffee

R. rosea

extract

and

Rhaponticum

cartamoides

extract

S. chinensis

berry

dry,

S. chinensis

berry

tincture

S. chinensis

berry

decoction

S. chinensis

seed

tincture

Water and 70%

ethanol (controls)

S. chinensis

seed

powder

Panax ginseng

tincture

S. chinensis

seed

powder, 0.5 g in

capsules

Acute and

repeated

Acute and

10 days

Acute

Acute and

multiple

IIb

IIa

IIb

IIa

Grigorenko and

Berdyshev, 1988

Kaliko and

Tarasova, 1966

Karo, 1945;

Lazarev, 1946

Kochmareva,

1958

Kokhanova

et al.

, 1950

S. chinensis

showed a tonic effect for 4–7 h

in those on night duties.

E. senticosus

was

inactive

Repeated uptake (for more than 2 weeks)

of coffee and

S. chinensis

produced similar

negative effects (insomnia, excitability, etc.)

Single and repeated administration of

adaptogens improved functional state of the

CNS in patients with neurosis as characterized

by normalization of the speed and power

of neural processes in Ivanov-Smolenski’s

verbal test with speech-supported

locomotor-conditioned reﬂex measurement.

The memory improved and attention became

more stable

Increased physical working capacity

and physical force of men 1–3 h after

administration; tincture of

S. chinensis

seed

was most active

Improved attention in text correction 2 h after

drug administration. Both extracts increased

quality and quantity of mental work

performed

Increased physical working capacity starting

from 2.5 h after single dose administration

and lasting for 3 h. More pronounced effect

was established against a background of

fatigue. After multiple administration

S. chinensis

showed no stimulating effect

824 A. PANOSSIAN AND H. WAGNER

Classiﬁcation of

evidence level

according to

WHO, FDA

and EMEA

IIa

IIb

III

IIa

III

IIa

IIb

Table 1. (continued)

Reference to

study

Study

design

Number of

subjects in

the study (

)

Age range

of subjects Daily dose

Type of preparation

tested

Duration

of study Effects recorded

Komar

et al.

1981

Lebedev, 1951a

Lebedev, 1967

Lebedev, 1955

Lebedev, 1967

Marina

et al.

1994

Medvedev, 1963

Murtazin, 1946

254

125

Study A 45

soldiers;

Study B

58 subjects

C, open

CO, PC

PC, SB,

19–22

21–22

21–24

21–23

20 drops

0.3 g

3g,

0.036– 0.168 g

0.02 g

0.01 g

0.005 g

0.02 g

0.5 g

30 mL

0.02 g

0.5 g

1, 5, 10 and

20 mg

5 drops

2mL

6 capsules

Rhodiola rosea

40%

ethanol tincture

E. senticosus

40%

ethanol tincture

Extract of

R. rosea

rhizome

S. chinensis

seed,

extract and fractions,

tablets and capsules

Schizandrin

Phenamine

Glucose

S. chinensis

seed

tincture

P. ginseng

, 3% tincture

Phenamine

Glucose

Tyrosol

R. rosea

extract

E. senticosus

tincture

P. ginseng

tincture

S. chinensis

seed

powder, 1 g in

capsules

Acute

Improved mental performance; reduced the

number of errors in Anﬁmov’s correction test;

increased the accuracy, working capacity and

speed of information perception. Stimulating

effect lasted 4 h or more

Improved accuracy in error correction test.

Most active stimulating effect was revealed by

a crystalline substance identiﬁed as the lignan

schizandrin

Schizandrin improved accuracy in the work of

telegraph operators at exhaustion compared

with control group and those given

phenamine

Schizandrin signiﬁcantly decreased running

time in a competition at 3000 m

cf.

with

control group

P. ginseng

and

S. chinensis

improved

accuracy in the work of telegraph operators

at exhaustion compared with controls and

phenamine

Improved mental performance, reduced the

number of errors in Anﬁmov’s correction test

Decreased errors in data sent by radio

operators 1 h after drug uptake. Stimulating

effect of

E. senticosus

was stronger and more

stable than the effect of Ginseng, which was

insigniﬁcant

Mean running time of verum group was

shorter than that of the control group in a

20 km marathon ski under stress conditions.

Fatigue, muscular pain, shortness of breath

and dryness of the mouth were reduced

STIMULATING EFFECT OF ADAPTOGENS 825

Classiﬁcation of

evidence level

according to

WHO, FDA

and EMEA

IIa

IIb

Table 1. (continued)

Reference to

study

Study

design

Number of

subjects in

the study (

)

Age range

of subjects Daily dose

Type of preparation

tested

Duration

of study Effects recorded

Roslyakova

et al.

, 2000

Shevtsov

et al.

, 2003

Strokina, 1967

Trusov, 1953

Trusov, 1958a

Tuzov, 1968

Yeﬁmova

et al.

, 1954

Zotova, 1965

?, data not listed or unavailable; CO, crossover; DB, double-blind; SB, single blind, NC, not controlled; PC, placebo-controlled; C, controlled; R, randomized.

Ia, Meta-analyses of randomized and controlled studies; Ib, Evidence from at least one randomized study with control; IIa, Evidence from at least one well-performed study with control

group; IIb, Evidence from at least one well-performed quasi-experimental study; III, Evidence from well-performed non-experimental descriptive studies as well as comparative studies,

correlation studies and case-studies; and IV, Evidence from expert committee reports or appraisals and/or clinical experiences by prominent authorities.

161

120 pilots

150 healthy

males

PC, DB

DB, R,

PC, DB

PC, SB

PC, SB,

PC, CO,

19–21

23–55

21–26

18–24

20–22

20–28

2, 3 capsules

120 mg

2mL

15 drops

2mL

5–10 drops

Rodelim, ﬁxed

combination of

standardized extracts

Rhodiola rosea

E. senticosus

S. chinensis

, in tablets

Standardized

R. rosea

extract, 185 mg

in a capsule

E. senticosus

dry

extract

S. chinensis

seed

powder, capsules

S. chinensis

seed

powder, capsules

E. senticosus

extract

Rhodiola rosea

, extract

Rhaponticum

cartamoides

extract

P. ginseng

extract

Pyridrol

S. chinensis

seed

powder, 0.5 g in

capsules

Rhodiola rosea

40%

ethanol tincture

Acute

Acute and

3 weeks

Acute

Acute and

repeated

Acute

Rodelim improved mental working capacity

in computer and correction tests against a

background of fatigue

Improved visual perception, short term

memory capacity, attention span and ability to

switch attention and anti-fatigue effect in the

psychometric tests

Improved mental performance determined by

a letter correction test

Improved night vision 50–70 min after

administration by some 1.5–2-fold for 7–8 h

Improved eye retina sensitivity to light under

dark conditions for 3.5 h in 90% of subjects

1.5 h after drug administration

Rhodiola rosea

E. senticosus

and

Rhaponticum cartamoides

increased working

capacity at maximal intensity for 30 s (sprint)

and duration of work of preset high-intensity

35 min after administration. The effects were

more signiﬁcant under conditions of fatigue

Increased physical working capacity by up to

222%

cf.

with control. After repeated

administration

S. chinensis

did not increase

working capacity, but after a wash-out period,

the stimulating effect returned

Improved mental performance, reduced the

number of errors in Anﬁmov’s correction test:

the stimulating effect lasted 4 h or more

826 A. PANOSSIAN AND H. WAGNER

Table 2. The difference between adaptogens and other stimulants

Stimulants Adaptogens

1. Recovery process after exhaustive physical load Low High

2. Energy depletion Yes No

3. Performance in stress Decrease Increase

4. Survival in stress Decrease Increase

5. Quality of arousal Bad Good

6. Insomnia Yes No

7. Side effects Yes No

8. DNA/RNA and protein synthesis Decrease Increase

et al., 1985; Wagner et al., 1994; Panossian et al., 1999c;

Panossian, 2003). Depending on the mediators of

the stress-system involved in the adaptogen-induced

stress-response, an immediate (single dose effect) or a

long term (after multiple administration) stimulating

effect may be observed. Whilst the efﬁcacy of repeated

administration of adaptogens in improving mental per-

formance over various time periods is well documented

(Darbinyan et al., 2000; Spasov et al., 2000a, b), reports

on single dose effects are fragmentary and have yet

to be given comprehensive consideration. This article

reviews the results that have been recorded in human

subjects and, to a lesser extent, in laboratory animals

following single treatment with plant adaptogens.

STUDIES INVOLVING ANIMAL MODELS

It has been shown that small doses of an extract of

R. rosea, or of its active ingredient salidroside (1),

increases the spontaneous bio-electrical activity of

the brains of test animals, presumably by direct effects

on the ascending and descending reticular forma-

tion in the brainstem (Saratikov et al., 1965, 1978;

Marina, 1968; Marina and Alekseeva, 1968). Unlike

tranquillizers, however, medium range doses of the

adaptogen enhance the development of conditioned

avoidance reﬂexes in rats, and facilitate learning based

on positive reinforcement (Saratikov et al., 1965). In a

staircase experiment, involving a device consisting of

13 steps and four feeders, rats were starved for 23 h

and then trained to climb to the 12th step in order to

receive their food ration: one training session was

carried out with each animal for 5 successive days and

the criterion for learning was the number of trained

animals recorded on day 5 (Petkov et al., 1986). With

positive (food) reinforcement, a single administration

of an extract of R. rosea (0.1 mL per animal ) produced

a signiﬁcant increase in the number of trained animals

(Fig. 1). In passive avoidance tests, however, no sig-

niﬁcant differences were recorded between the control

animals and those treated with multiple administrations

for up to 10 days. The results obtained clearly depended

on the test methods employed and the differences noted

could indicate different neurochemical mechanisms

underlying the training methods.

In a maze test with negative (punitive) reinforcement,

signiﬁcant enhancements in learning and retention were

detected in rats following the single dose application of

an extract of R. rosea at a rate of 0.1 mL per animal

(Petkov et al., 1986). The experiments were carried out

using a multi-chamber, semi-automatic maze: a quiet

Figure 1. The effect of an extract of

Rhodiola rosea

on learning

in rats using an active avoidance method with positive (food)

reinforcement. (Figure drawn from the data of Petkov

et al.

1986.)

buzzer was used as the conditional signal, followed by

punitive reinforcement in the form of a small electrical

current on the ﬂoor grid that was maintained until the

rat entered the goal-section of the maze. Training was

performed in one session until the test animal had found

its way to the goal-section in six successive attempts.

Retention parameters were considered to be the number

of correct responses (entry of the test animal into the

goal-section) and their latencies 24 h after training, and

these parameters improved signiﬁcantly following treat-

ment with the plant adaptogen (Figs 2 and 3). Repeated

administration of the drug at the same dose level showed

similar effects.

Extracts of R. rosea have been reported to exhibit

interesting dose-dependent effects on the duration of

thiopental-induced sleep in mice (Fig. 4), ranging from

stimulation at low doses (10 mg/kg), where the sleep

period was reduced by 12.5 times, to sedation at high

doses (500 mg/kg), where the sleep period was increased

3-fold (Kurkin et al., 2003).

Ten days after oral administration of an aqueous

extract of R. rosea, the levels of norepinephrine (NE),

dopamine (DA) and serotonin (5-HT) in the brainstem

of the experimental animals increased considerably

compared with the levels in the same cerebral structure

in control animals. In the cerebral cortex, the levels of

NE and DA decreased signiﬁcantly, whilst the 5-HT

level increased sharply. In contrast, in the hypothalamus

of rats treated with extracts of R. rosea, the formation

of NE and of DA increased about 3-fold compared

with the control group, whilst the 5-HT content de-

creased (Stancheva and Mosharrof, 1987). Treatment

with adaptogen also enhanced the effects of neuro-

transmitters on the brain by increasing the per-

meability of the blood–brain barrier to precursors

of DA and 5-HT. It has been suggested (Saratikov

et al., 1965, 1978; Marina, 1968; Marina and Alekseeva,

1968; Saratikov and Krasnov, 2004; Kurkin and

STIMULATING EFFECT OF ADAPTOGENS 827

Figure 2. The effect of an extract of

Rhodiola rosea

on learning in rats in experiments involving active avoidance tasks with negative

(punitive) reinforcement. Maze training started 30 min after oral administration of

R. rosea

extract. Values shown are mean ± SEM.

(Figure drawn from the data of Petkov

et al.

, 1986.)

Figure 3. The effect of an extract of

Rhodiola rosea

on memory in rats in experiments involving active avoidance tasks with negative

(punitive) reinforcement. The memory test was applied 24 h after training and on 9 subsequent days following the ﬁrst retention test:

maze training started 30 min after oral administration of preparation. Values shown are mean ± SEM. (Figure drawn from the data

of Petkov

et al.

, 1986.)

been demonstrated that 4 exhibited the largest stimu-

lating effect after a single oral administration (Figs 7–9;

Sokolov et al., 1990, Zapesochnaya et al., 1995) and

also showed the highest bioavailability (Zapesochnaya

et al., 1995). Moreover, whilst nearly all of the 27 pure

compounds isolated from R. sachalinensis (including 1

and 2) screened against propyl endoperoxidase (which

is known to play a role in the degradation of proline-

containing neuropeptides involved in the process of

learning and memory) showed inhibitory activity, the

most potent was 1,2,3,6-tetragogouyl-glucose (Fan et al.,

2001).

STUDIES INVOLVING HUMAN SUBJECTS

The results of such studies are summarized in Table 1

in which the type and level of evidence gathered has

been classiﬁed according to the WHO, FDA and EMEA

systems. The most important effects reported were

increases in: (i) mental working capacity, (ii) physical

working capacity, (iii) the accuracy of movement, and

(iv) the visual functions of the eye.

Effect of adaptogens on mental working capacity

The effect of a single dose of an extract of R. rosea

on the mental performance of 85 healthy males and

females, in the age range 20–28 years old and working

under the same conditions, was studied by Zotova (1965)

using Anﬁmov’s table, which provides the possibility

of obtaining numerically comparable data characteriz-

ing the quality and quantity of work performed. The

subjects were asked to cross through letters A and C in

Figure 4. The effect of a single dose of

Rhodiola rosea

extract (administered 30 min before thiopental) on thiopental

(50 mg/kg, i.abd.) induced sleep in mice. The duration of sleep

was measured by the time that each animal remained laying

on its side. (Figure drawn from the data of Petkov

et al.

, 1986.)

Zapesochnaya, 1986) that treatment with extracts of R.

rosea promotes the release of NE, DA and 5-HT in the

ascending pathways of the brainstem thus activating

the cerebral cortex and the limbic system. Consequently,

the cognitive functions (thinking, analysing, evaluating,

calculating and planning) of the cerebral cortex, and

the attention, memory and learning functions of the

prefrontal and frontal cortex are enhanced.

Using animal models, bioassay-guided fractionation

of various extracts of plant adaptogens has shown

that the active principles are mainly phenylpropane

and phenylethane derivatives including salidroside (1),

rosavin (2), syringin (3), triandrin (4), tyrosol (5), etc

(Lebedev, 1951a, 1967; Aksenova, 1969; Aksenova et al.,

1968; Dardymov, 1976; Kurkin and Zapesochnaya,

1986; Nishibe et al., 1990; Zapesochnaya et al., 1995;

Saratikov and Krasnov, 2004). Of these, 1 was reported

to be the most active in a number of different test

systems (Figs 5 and 6; Barnaulov et al., 1986). How-

ever, in a more recent comparative study, it has

828 A. PANOSSIAN AND H. WAGNER

Figure 5. (a) The stimulating effect of salidroside on mice kept continuously on poles until complete exhaustion; (b) The anti-hypnotic

effect of salidroside (s.c. injection at a dose of 100 mg/ kg) and of Rhodiola administered 1 h before the induction of sleep in mice

by Medinal. (Figure drawn from the data of Barnaulov

et al.

, 1986.)

Figure 6. The stimulating effects of compounds isolated from

roots of

Rhodiola rosea

. Preparations were administered six

times within 3 days to the test animals and their investigated

behaviour compared with that of a control group of rats. Sub-

jects were assessed using a ‘free ﬁeld’ method involving count-

ing the number of oriented standing up activities and entries

into segments of an arena for 3 min. On day 4, the drug was

administered to the rats who were then subjected to an electri-

cal current (12 mA for 10 s), in order to decrease their uncondi-

tioned oriented reﬂex, and ‘free ﬁeld’ counting was conducted

15 min after the electrotrauma. (Figure drawn from the data of

Barnaulov

et al.

, 1986.)

Figure 7. The effect on spontaneous movement activity in rats

after single dose administration of triandrin, rosavin and

syringin. (Figure drawn from the data of Sokolov

et al.

, 1990.)

Figure 9. The stimulating effect of triandrin, rosavin, syringin and cinnamoyl alcohol after single dose administration to sodium

barbital anaesthetized mice. (Figure drawn from the data of Sokolov

et al.

, 1990.)

Figure 8. The arousing effect of triandrin, rosavin and syringin after single dose administration to chloral-hydrate anaesthetized mice.

Values shown are mean ± SEM. (Figure drawn from the data of Sokolov

et al.

, 1990.)

a text within a ﬁxed time of 5 min. Subjects were

grouped, and each group was treated separately with

different doses of R. rosea extract and ﬁnally with

placebo (coloured, 40% aqueous alcohol): in this

manner, any possible improvement in the results

occasioned by learning how to perform the test were

STIMULATING EFFECT OF ADAPTOGENS 829

eliminated. Each subject performed the task twice, once

before treatment with the extract/placebo and a second

time 1 h after the treatment. The results indicated that,

compared with treatment with the placebo, applica-

tion of R. rosea extract did not affect the quantity of

characters correctly crossed through, but considerably

reduced the number of errors made. Doses of 5–10

drops were found to be the most effective, reducing

the number of errors by an average of 46% (Fig. 10a).

At a dose of 5 drops, the treatment with the extract led

to a reduction in the number of errors in 88% of the

subjects tested, but to an increase in the remaining 12%.

Application of the placebo produced a reduction in the

number of errors in 35% of the subjects, an increase

in 58% and no change in the remaining 7% (Fig. 10b).

It was found that at a dose of 7 drops, the extract

exhibited a pronounced stimulating effect that lasted

some 4 h or longer (Zotova, 1965). In a complementary

study, the effect of salidroside (1) alone was shown to

be highly comparable to that of the extract of R. rosea

(Fig. 10) (Aksenova et al., 1968).

A similar study protocol was employed by Komar

et al. (1981) in order to compare the effects of pre-

parations of R. rosea and Eleutherococcus senticosus

on human mental activity. In this work, 254 men and

women were treated with an adaptogen extract or with

a tincture of Mentha as the control. The R. rosea ex-

tract was more active than that of E. senticosus in terms

of increasing working capacity (the difference in the

number of corrected symbols), efﬁcacy (performance,

decreasing the number of errors) and speed of infor-

mation processing and perception. Unfortunately, it

was not stated if the trial was randomized and blind,

or if the differences between the results of the verum

and control groups were statistically signiﬁcant. From

a separate series of tests conducted up to 8 h after

administration of the R. rosea extract, the same authors

claimed that the stimulating effect lasted for at least

4h, but again the statistical status of the signiﬁcance of

these results remains unknown.

In another study involving text correction using

Anﬁmov’s tables and the ability to memorize paragraphs

of text, 82 volunteers were treated with either 5 drops

of extract of R. rosea or a dose (1, 5, 10 or 20 mg) of

pure tyrosol (5; an active component of R. rosea)

(Marina et al., 1994). The mental working capacities of

the subjects were evaluated after treatment, and it was

demonstrated that whilst neither preparation produced

an effect on the time taken to perform the correction

task, both improved the quality of performance, reduc-

ing the percentage of errors by 29%–35% compared

with the control, and increasing the volume of the

short-term memory as represented by the number

of text paragraphs recalled. The differences between

the results of groups taking different doses of 5 and

of the extract were not statistically signiﬁcant (Marina

et al., 1994).

More recently, a randomized, double-blind, placebo-

controlled parallel group clinical study with an extra

non-treatment control group was performed (Shevtsov

et al., 2003) in order to measure the effect of a single

dose (2 or 3 capsules) of a standardized extract of

R. rosea (SHR-5; 180 mg per gelatine capsule) on the

capacity for mental (psychometric tests) work against a

background of fatigue and stress. The analysis, which

involved 161 cadets, demonstrated that both doses of

the extract produced statistically signiﬁcant ( p < 0.001)

anti-fatigue (stimulating) effects, together with similarly

signiﬁcant beneﬁcial effects on pulse pressure, compared

with the placebo.

In 1988, Grigorenko and Berdyshev, reported that

a single daily dose of S. chinensis tea produced, for

at least the ﬁrst 7–10 days of treatment, a tonic effect in

sailors who were keeping watch. After 2–3 weeks of

continuous use of the tea, some subjects developed

sleeplessness, excitability and a low level of general well-

being, although these negative side effects could be

eliminated by interludes with black tea. In an extension

to this work, a systematic placebo-controlled cross-over

study of various aspects of single dose administration

of both E. senticosus and S. chinensis on the mental

performance of 357 sailors on watch duty was performed

(Berdyshev, 1995). Subjects took different doses of the

preparations prior to their watch period and, 30–60 min

before such administration, a correction test was used

to evaluate mental performance. A similar correction

test was conducted immediately (30–60 min) after the

watch, and subjects were further tested before and

after watch duty every 4–5 days in order to exclude a

possible cumulative effect of the treatment.

Single doses of between 0.25 and 8 mL of E. senticosus

extract were administered to sailors before the watch,

and a dose of 4 ml was found to be the most effective

in improving working ability. Doses up to 1 mL did not

have the desired effect on most of the subjects, whilst

doses larger than 4 mL did not improve the results in

the test group. At a dose of 8 mL, only 49% of subjects

showed a positive effect and, moreover, the subjective

condition and several objective parameters of some

subjects in this group (11 out of 62) became worse, i.e.

for a short period (20–40 min) the subjects felt sleepy

and ﬂabby, whilst the indirect parameters associated

with their working ability and blood pressure decreased.

In order to study the daily dynamics of the effect of

a single 4 mL dose of E. senticosus extract, additional

studies were carried out involving 72 of the original

sailors carrying out similar tasks inside the ship whilst

on different watches. The considerable differences

revealed in the efﬁcacy of E. senticosus were found to

be related to the individual typological features of the

subject, including daily and seasonal biorhythms. In the

morning, positive effects on working ability occasioned

by the adaptogen were most pronounced in subjects

presenting the morning type of biorhythmic activity

(83% of the subjects) compared with only 39% of

the subjects exhibiting the evening type of activity. In

Figure 10. The effect of a single dose of

Rhodiola rosea

extract

(10 drops) and salidroside (2.5 mg) on the mental performances

of 46 healthy subjects as measured by a text correction test

applied 1 h after administration in comparison with a control

test applied 1 h before administration. (Figure drawn from the

data of Aksenova

et al.

, 1968.)

830 A. PANOSSIAN AND H. WAGNER

the evening, the results were quite different in that the

adaptogen showed much better results in subjects with

the evening type of biorhythmic activity. At night, when

the overall effect of the preparation was relatively

low, the correlation with biorhythmic type practically

disappeared.

In order to determine if the efﬁcacy of the extract of

E. senticosus was associated with the functional state

of the organism, a correlation analysis was carried out

on the same group of sailors with respect to the initial

(before work) values of various biochemical parameters

(Table 3). For sailors working on all watches, positive

relationships between the efﬁcacy of the adaptogen

and the activity of the adrenal cortex (excretion of

17-ketosteroids in the urine), the activity of the sympa-

thetic adrenomedullar system (orthostatic test), the

intensity of metabolic processes (excretion of vitamin

C in the urine) and the intensity of oxidation-reduction

processes (Rotter test) could be demonstrated. In con-

trast, the activity of the parasympathetic nervous system

(clinostatic test), non-speciﬁc resistance (percentage

phagocytosis, phagocytic index, vascular resistance, and

osmotic resistance of erythrocytes) and the endurance

to hypoxia (Hench test with retention of breathing

at exhalation) all showed negative correlations with

efﬁcacy of the drug.

In a similar, comparative analysis (Berdyshev, 1995),

44 sailors (whose duties involved hard work under

severe winter conditions) were administered placebo,

4mL of E. senticosus extract, or 3 mL of S. chinensis

tincture, each on a separate test day, and then exam-

ined before and after completing their watches. Using

a paired correlation method, the relationship between

the effect of the adaptogens (determined individually

according to the working ability of the subject) and

the differences in functional changes during the watch

(compared with the placebo values for that subject)

were calculated for each sailor (Table 4). On the basis

Table 3. The values of the correlation coefﬁcients associated with comparisons of effects of

Eleutherococcus senticosus extract (4 mL) and initial levels of functional parameters in sailors

during watches in middle altitudes

Correlation coefﬁcient

Parameter Morning (8:00) Evening (20:00) Night (4:00)

Excretion of 17-ketosteroids in urine 0.57 0.31 0.22

Eosinophils of the blood −0.22 −0.35 −0.26

Orthostatic test 0.59 0.63 0.31

Clinostatic test −0.68 −0.52 −0.36

Vitamin C excretion in urine 0.62 0.37 0.17

Rotter test −0.55 −0.4 −0.21

Hench test −0.48 −0.25 −0.12

Phagocytosis percentage −0.41 −0.34 −0.23

Phagocytic index −0.55 −0.43 −0.28

Vascular resistance −0.53 −0.36 −0.32

Osmotic resistance of erythrocytes −0.66 −0.42 −0.2

Table 4. The values of correlation index between the effects of Eleutherococcus senticosus and

Schizandra chinensis extracts and changes in functional parameters during a day watch under

unfavourable conditions

Index of pair correlation

Eleutherococcus Schizandra

Parameter

senticosus chinensis

Excretion of 17-ketosteroids in urine −0.55 0.21

Eosinophils of the blood 0.42 −0.16

Energy metabolism 0.34 0.83

Rotter test −0.33 −0.59

Respiration coefﬁcient 0.15 0.5

Tonus of the sympathetic adrenomedullar system −0.27 0.78

Tonus of the parasympathetic nervous system 0.69 −0.21

Vitamin C excretion in urine −0.22 0.4

Total nitrogen excretion in urine −0.3 0.38

Breathing retention at exhalation 0.58 −0.35

Phagocytosis percentage 0.41 −0.24

Phagocytic index 0.53 −0.16

Vascular resistance 0.39 −0.4

Osmotic erythrocyte resistance 0.45 −0.27

CNS excitation 0.21 0.69

Excitation/inhibition balance in the CNS 0.48 −0.17

Heart rate −0.36 0.49

Systolic blood pressure 0.18 0.45

Coefﬁcient of the cardiovascular system endurance −0.46 −0.29

Body temperature −0.3 0.37

STIMULATING EFFECT OF ADAPTOGENS 831

of these results, the author suggested that in subjects

working under stress the effect of a single dose of

E. senticosus was occasioned by a pronounced increase

in the tonus of the parasympathetic part of the auto-

nomic nervous system, a moderate intensiﬁcation of

excitation of the CNS and of energy metabolism with

practically unchanged respiratory coefﬁcient, a tendency

towards the intensiﬁcation of oxidation-reduction pro-

cesses in tissues, improvement of cortical processes and

balance, and in cardiovascular system activity thanks to

slower pulse and increased pulse pressure, a decrease

in adrenal cortex activity, catabolic processes, and

the tonus of the sympathetic part of the autonomic

nervous system, and a reduction in the increase of body

temperature. It was concluded that the increase in work-

ing ability following treatment with the adaptogen

was associated with improved endurance to hypoxia

and improvement in the parameters of non-speciﬁc

resistance of the subject. Furthermore, treatment with

an extract of E. senticosus was claimed to reduce exces-

sive exertion of the organism by virtue of its effect on

adrenal function and tonus of the autonomic nervous

system.

On the other hand, the results of the correlation

analysis suggested that the increase in work capacity

induced by a single dose of S. chinensis was brought

about by a quite different mechanism. Thus, improve-

ment in mental performance correlated positively with

increased energy metabolism and catabolic processes,

increased tonus of the CNS, and intensiﬁed activities of

the sympathetic adrenomedullar, the adrenal and the

cardiovascular systems. This, in turn, coincided with an

increase in body temperature, a lowered endurance to

hypoxia, and a decrease in some parameters of non-

speciﬁc resistance of the subject. These facts indicate

that the effects of this adaptogen are associated with

the additional mobilization of energy resources, i.e.

S. chinensis is, evidently, a mild stimulant.

The differences in the effects produced by E.

senticosus and by S. chinensis on working ability and

function of subjects at night time can be explained

in terms of the differences in mechanism of action

of the two drugs. Table 5 shows the levels of various

functional parameters determined in groups of sailors

after performing their duties under conditions of

high temperature and humidity between the hours of

midnight and 4 a.m. (Berdyshev, 1995). The subjects

were administered either a placebo or one of the test

drugs directly before their watch, and were examined

immediately after having performed their duty (between

4 and 5 a.m). The results show that, in contrast to E.

senticosus, treatment with S. chinensis stimulated the

activity of the CNS at night (activated excitation proc-

esses and normalized nervous processes ratio), increased

tonus of the sympathetic part of the autonomic nerv-

ous system (having no effect on the parasympathetic

part), activated the adrenal cortex activity, increased

the activity of the cardiovascular and respiratory sys-

tems, intensiﬁed oxidation-reduction and metabolic

processes, improved working ability parameters and, at

the same time, reduced parameters of non-speciﬁc re-

sistance the organism and cellular structure resistance

and increased body temperature (Berdyshev, 1995).

Differences in the stimulating effects of various

adaptogens following single administration were demon-

strated by Medvedev (1963) in a study involving radio

operators. It was shown that, compared with placebo,

an extract of E. senticosus signiﬁcantly decreased the

number of errors in messages transmitted by tired

operators. The stimulating effect of E. senticosus

was strong and stable whilst that produced by Panax

ginseng was insigniﬁcant (Fig. 11).

A series of in-depth studies have been carried out

at the Centre for Space Medicine of the Institute of

Medicinal and Biological Problems (IMBD) and at the

Moscow Aviation Institute (Bogatova and Malozemov,

1994; Bogatova et al., 1997) in order to evaluate the

effect of a ﬁxed and standardized combination of

extracts of S. chinensis, E. senticosus and R. rosea

[ADAPT-232; capsules containing 3 mg of salidroside

(1), 4 mg of schizandrin (6) and 3 mg eleutheroside B

(7)]. The consequence on short-term memory, power

Table 5. Effects of extracts of Eleutherococcus senticosus and Schizandra chinensis on functional parameters in sailors during night

watches in middle latitudes

After a night watch (4:00)

Eleutherococcus Schizandra

Parameter Control

senticosus chinensis

Time of a simple sensorimotor response (ms) 230 ± 1.0 226 ± 1.4 212 ± 2.3a

Endurance to static effort (s) 24.9 ± 0.5 25.6 ± 0.6 27.8 ± 0.6a

Hench test (s) 26.8 ± 0.5 28.9 ± 0.4 26.5 ± 0.6a

Body temperature (°C) 36.30 ± 0.01 36.30 ± 0.01 36.60 ± 0.02a

Heart rate (bpm) 66.2 ± 0.8 68.4 ± 0.9 72.8 ± 1.1a

Systolic pressure (mm Hg) 100 ± 0.8 104 ± 1.3 108 ± 1.3a

Diastolic pressure (mm Hg) 60.5 ± 0.7 62.0 ± 0.9 70.0 ± 1.1a

Orthostatic test (bpm) 13.1 ± 0.6 14.1 ± 0.8 18.2 ± 0.9a

Clinostatic test (bpm) 16.5 ± 1.0 16.4 ± 1.1 16.2 ± 0.8

Respiration rate (breath/min) 12.4 ± 0.7 13.2 ± 0.6 15.6 ± 0.7a

Diuresis (mL/h) 32.0 ± 2.0 33.5 ± 2.3 41.5 ± 2.5a

Vitamin C excretion in urine (mg/h) 0.41 ± 0.02 0.43 ± 0.02 0.62 ± 0.02a

Excretion of 17-ketosteroids in urine 0.59 ± 0.01 0.52 ± 0.02 0.75 ± 0.03a

Phagocytosis percentage 60 ± 2.4 71 ± 2.8 53 ± 2.4a

Phagocytic index 13 ± 0.57 19 ± 0.62 12 ± 0.55a

Rotter test (min) 14.1 ± 1.3 13.6 ± 0.9 10.5 ± 0.7a

< 0.05

832 A. PANOSSIAN AND H. WAGNER

of comprehension, and oculomotor coordination in

ﬁve Russian cosmonauts treated with a single dose of

ADAPT-232 during their training in prolonged isola-

tion (90 days) under conditions of long-term, monoto-

nous work was evaluated in a placebo-controlled pilot

study. Computer-generated psychometric tests were

carried out at various times after treatment of the sub-

jects and the results demonstrated that, within 4 h of

application, ADAPT-232 signiﬁcantly decreased the

number of mistakes in complicated psychometric tests

but had no signiﬁcant effect in non-complicated tests.

In a follow-up study, 60 volunteers, selected from

a population of 97 on the basis of high results (≥7.5

out of 10) in a psychometric test, were divided into

six equal groups and each group was tested against

itself after taking ADAPT-232 (3 capsules once a day)

or placebo according to a cross-over design with a

wash-out period of 3 days. The study consisted of three

sections: (i) examination of mental performance during

24 h continuous work after a single-dose treatment,

(ii) examination of the mental and physical (mainly

cardiovascular) work capacity against a background of

fatigue or/and stress during repeated-dose treatment,

and (iii) assessment of the well-being of treated sub-

jects as determined from their subjective view of the

level of difﬁculty of the tests applied. The main aim of

the study was to determine the effect of adaptogens

during monotonous and long-term work under con-

ditions that simulated the environment on the space

stations SaIjut and Mir. For this purpose a highly

sophisticated computer-based test (Monotonic 2) was

employed, which consisted of a well-tried and validated

battery of assessments measuring mental performance

during space-like conditions.

Monotonic 2 was developed and reﬁned over a

period of 20 years and has proven to be much more

reliable than standard tests with pencil and paper.

The most important parameters assessed are speed,

reliability and the ability to comprehend, learn and

reproduce new information with high precision during

monotonous and long working shifts. In order to study

the dynamics of a single dose effect, as well as the on-

set of an effect, each subject performed 18 h of mono-

tonous work and then had to respond to the computer

program continuously during the test (which started at

2 a.m.). Scores representing (i) speed and reliability in

the understanding of information (t), and (ii) precision

and accuracy in the ability to reproduce the informa-

tion (h), were recorded every 30 min for each subject.

The lower the value of t, the higher the speed; the

higher the value of h, the higher the precision: taken

together, the values of t and h also provided an indica-

tor of the level of tiredness and concentration in

repeated tests. The results of the Monotonic 2 test con-

cerning mental work capacity are shown in Fig. 12 in

which the mean data for each group are displayed.

Regarding the on-set of the effect, the tests revealed a

signiﬁcant increase in performance after 1–2 h. With

respect to the parameters of speed and precision, an

increase in mental work capacity after intake of

ADAPT-232 is clearly seen in Fig. 12 from the dif-

ference in area between the two curves.

An alternative ﬁxed and standardized combination

of extracts of S. chinensis, E. senticosus and R. rosea

(Rodelim) has also been shown to increase signiﬁcantly

the mental working capacity of healthy volunteers when

applied in repeated or single-dose format (Vezirishvili

et al., 1999; Roslyakova et al., 2000). The assessment

was based on a study of the psycho-emotional and

psycho-physiological states, the professional and mental

working capacity, and the cardiovascular system of 60

computer operators on night duty under conditions that

simulated long monotonous activity inducing fatigue.

The methods of evaluation included mathematical ana-

lysis of the cardiac rhythm, computer tests, question-

naires and psycho-physiological tests, ophthalmologic

examinations and medical tests (heart rate, ECG and

respiration parameters, blood pressure, etc).

The effects of powdered seeds of S. chinensis on the

mental working capacity of 59 students was studied

(Lebedev, 1951a, b; Kochmareva, 1958) using a method

of text correction in which fatigue decreased the

accuracy but not the speed of work. Following treat-

ment, the performance of 38 subjects (65%) improved,

17 showing an increase in the number and quality of

corrections made, 14 demonstrating an improvement

only in quality of correction, and 7 an increase only in

Figure 11. The effects of extracts of

Eleutherococcus

senticosus

and

Panax ginseng

on the mental performance of radio opera-

tors assessed 1 h after drug uptake. (Figure drawn from the

data of Medvedev, 1963.)

Figure 12. The dynamics of object-stimulus ﬁxation: measurements of speed and precision were assessed 30 min after intake of

ADAPT-232 and for the following 4.5 h. (Figure reproduced from Bogatova

et al.

, 1994 with permission.)

STIMULATING EFFECT OF ADAPTOGENS 833

the amount of work performed. Six constituents were

isolated from the seeds of S. chinensis and the tests

repeated on 20 subjects, every one of whom received

each of the compounds individually. Schizandrin (6)

was found to be the most active substance present

in the seed material. A dose of 3.6 mg of 6 prevented

exhaustion-related errors in text correction by the sub-

jects: errors of the control group (treated with placebo)

amounted to 228% whilst those of the treated group

were only 95% (errors in the control test normalized to

100%) (Lebedev, 1951a, b, 1967).

In another study, involving telegraph operators

between the ages of 21 and 24 years, the same author

showed that single doses of either an extract of S.

chinensis (30 mL; 10% in 70% aqueous ethanol) or of

compound 6 (5, 10 and 20 mg) prevented exhaustion-

related errors in transmitting Morse code at maximum

speed for 5 min (Lebedev, 1967). In this duplicated

set of experiments (n1 = 20, n2 = 23) the frequency of

errors made by the control groups (given glucose or

70% aqueous ethanol as placebo) was 130%, whilst the

error frequency of the treated groups was 84%–103%

(errors in the control test normalized to 100%). Similar

results were obtained following treatment of the opera-

tors with P. ginseng or with phenamine: however, the

latter produced an effect of excitation that increased

speed but not performance.

Along with the demonstration that adaptogens

could improve mental capacity of healthy subjects, a

number of Russian researchers conceived the idea that

they could be used for the treatment of some neurotic

conditions. Kaliko and Tarasova (1966) studied the

effects of extracts of R. rosea and Rhaponticum carta-

moides on 80 healthy students and 70 neurotic patients

employing the so-called Ivanov-Smolenski verbal ex-

periment with speech-supported locomotor-conditioned

reﬂex measurement. In this test, 25 words conveying

exciting images were located in sequence with words

requiring a reﬂective oral response from the subject.

Excitation was assessed by the speed of formation, sta-

bility and intensity of reﬂex movements, whilst calming

effects were determined from the latent period between

a questioning word and the response, and also from the

character of the response. The verbal experiment was

performed twice (using a different set of 25 words on

each occasion) with each participant, once before drug

administration and once following a single or repeated

dose of the extract. It was found that, in single dose

form, neither extract induced an effect on the function-

ing of the CNS in healthy subjects. However, in patients

with neurosis, a single dose of Rhodiola rosea extract

brought about signiﬁcant changes in the functional state

of the CNS as characterized by normalization of the

speed and the power of neural processes. The latent

period of speech reﬂex decreased to between 1 and 3 s

(1.6 s was accepted as the normal latent period of speech

response), and stereotype answers and refusals dis-

appeared. Conditioned reﬂexes were formed at the ﬁrst

associations, their latent period decreased, the size of the

reﬂexes increased, generalized reactions disappeared,

transformation of positive-conditioned irritants into

negative ones arose after the ﬁrst associations, the

memory improved, and passive and (particularly)

active attention became more stable. Repeat testing

3 days after single dose administration showed that

the described improvement in functioning of the CNS

was only temporary (Kaliko and Tarasova, 1966). How-

ever, a more stable effect was achieved by multiple

administration of extracts of R. rosea and Rhaponticum

cartamoides over a 10 day period.

Effect of adaptogens on physical working capacity

Not only can the administration of plant adaptogens

improve mental performance, it can also stimulate

the brain cortex and thus increase physical capacity as

well. The working capacity and physical force of men

using the Dubua ergographic test was increased by 24%–

42% (cf control) after 1–3 h following administration

of a single dose of a 70% ethanol extract of the seeds

of S. chinensis (Karo, 1945; Lazarev, 1946): aqueous

extracts of seeds and extracts of berries, however,

showed no such activity. Following treatment with

capsules containing the powdered seeds of S. chinensis,

the stimulatory effect was observable within 2–2.5 h,

reached a maximum at 3.5 h and had disappeared

after 5.5 h (Kokhanova et al., 1950). Subjects who had

been fatigued by sawing wood for 5 min (at a frequency

of 45 saw movements/min) prior to treatment with S.

chinensis exhibited a more pronounced enhancement

of their working capacity (as measured by the Dubua

test), which increased from 27.5 kg/m in the control

group to 77 kg/m in the treated group.

Studies carried out using the classical ergometric bi-

cycle (60 kg load), in which the number of revolutions

completed by the subject was counted up to the point

of exhaustion, revealed an even greater stimulatory

effect of S. chinensis. Yeﬁmova et al. (1954) reported

that healthy subjects showed a more than 2-fold

increase in working capacity following administration

of a single dose of seed powder, whilst students tested

using similar methods exhibited an increase in working

capacity from 620 kg/m (mean control value for placebo

group) to 1736 kg/m. The classical ergographic proce-

dure was also used by Andrejev and Georgijev (1958)

who observed a 49.2% increase in the working capacity

of healthy subjects.

In athletes and rowers, a 20% tincture of S. chinensis

seed, administered in doses of 2, 5, 10 or 15 g and

applied 1, 2 or 3 h before physical exercise, improved

the function of the respiratory and cardio-vascular

systems, increased muscle power of the hand muscles,

and reduced the time required by the athletes to com-

plete the course (Eglit et al., 1965): the improvements

appeared to be particularly signiﬁcant for groups

of canoeists treated with the tincture 1 h before single-

handed races.

Powdered seed material of S. chinensis supplied in

capsule form to Red Army soldiers before they under-

took a 20 km ski run, reduced exhaustion and shortage

of breath, the feeling of thirst and dryness of the mouth,

and muscular pain compared with a control group who

had been given a placebo capsule (Murtazin, 1946). The

treated soldiers were able to complete the run in a

shorter time than the control group, and similar sets of

results were recorded for treated and control groups of

civilian skiers tested under the same conditions.

Results recorded for runners treated with pre-

parations of S. chinensis appear a little more complex,

however. Application of a tincture of S. chinensis pro-

duced a negative effect on the times taken for runners

834 A. PANOSSIAN AND H. WAGNER

to complete a 100 m course, but when the same sub-

jects were required to complete the longer distance of

1000 m, some 60% of the runners showed signiﬁcantly

improved times, and the overall average improvement

for all runners was 4.45 s (Astanin et al., 1943). After

receiving ethanol or caffeine, the times taken by these

runners to complete 1000 m were longer than those

recorded in preliminary runs (before which they had

received no treatment), and considerably longer than

the times recorded after receiving S. chinensis or am-

phetamine. In corroboration of these positive responses,

Lebedev (1967, 1971) reported that schizandrin (6: an

active component of S. chinensis) increased the work-

ing capacities of 20-year-old runners performing over a

distance of 3000 m such that their running times were

remarkably shorter than those of a control group that

had been treated with placebo (glucose). In all doses

tested, the stimulating effect of 6 was of the same order

of magnitude as that of phenamine.

A very detailed report is available concerning the

effects of E. senticosus on the activity of the cardio-

vascular system and the capacity for work of skiers. In

this study (Dalinger, 1966), groups of sportsmen took

part in one of a number of different events, i.e. ski

races of 20, 30 or 40 km, or a biathlon (a 20 km ski run

carrying a riﬂe and involving target shooting at various

locations during the race), or a 6-day ski hike over

150 km whilst carrying kit: each event was held under

severe conditions (air temperature of −28 to −23 °C with

a strong wind). Within each group, half were given an

alcohol extract of E. senticosus and the other half an

infusion of tea with a small amount of alcohol: both

preparations looked and tasted the same, and the skiers

did not know which they had been given. Before com-

mencing the competition, subjects underwent several

tests including a combined Letunov’s functional test,

oxyhemography with a functional test in the form of a

dosed delay of respiration for 50 s and a test with a

maximum delay of respiration (Stange’s test), whilst

the muscular tonus of the biceps and triceps brachia,

and the quadrate muscle of the thigh and the gastro-

cnemius was measured by means of a myotonometer

(Searman’s system). The tests were repeated immedi-

ately after completion of the event, during the ﬁrst

30 min and during the recovery period, and 6 h, 1 and

2 days later. The short-distance skiers were given their

preparation in the form of a single dose (4 mL) some

90, 60 or 45 min before the start of the event: the long-

distance skiers were given daily doses (2 mL each) of

preparation, the ﬁrst administration being 6 h after start-

ing the event, with a ﬁnal dose (4 mL) on the last day

of the hike.

Generally, those subjects who had received extract

of E. senticosus showed an increase in the capacity for

work (with easier breathing on the track), undertook

the ascents with greater energy, did not feel fatigue

after the extended work, noted a pronounced feeling

of muscular vigour, slept well, enjoyed a good appetite,

and were happy to return to training after completion of

the event. The athletes who had received the placebo

showed no such positive changes. The Letunov’s func-

tional test indicated that, in most cases, increases in

pulse rate and arterial pressure were less pronounced

in treated skiers in comparison with the appropriate

control group, and the elevated levels returned to

normal sooner (within 30–40 min rather than 80 min as

recorded for the control group). When subjected to

Stange’s test (at sub-maximal respiration) 30 min after

the event, athletes treated with E. senticosus presented

an average value of 110.8 s whilst the average value for

those given placebo was 103.9 s, indicating a higher

functional status of the cardio-vascular and nervous

system in the treated group. The oxyhemographic study

indicated that the adaptogen increased the athletes’

steadiness and resistance to hypoxemia. The results

of the delayed breathing test in combination with

oxyhemography, indicated an increase in resistance to

oxygen insufﬁciency in skiers who had taken the E.

senticosus extract, together with a more rapid restora-

tion of blood oxygenation after dosed delayed respira-

tion and after maximum delay of breathing.

An indication of the powerful restoring effect of the

adaptogen was demonstrated by its inﬂuence on mus-

cular tonus. After taking the preparation, skiers found

that it became easier to perform heavy muscular work

and the residual muscular tonus was less pronounced.

After 24 h there were practically no manifestations

of residual tonus in the treated skiers, whereas in the

athletes of the control group the residual tonus was still

somewhat pronounced. The decrease of the residual

tonus below initial values suggests that extracts of E.

senticosus stimulate a more active recovery following

heavy physical loading (Dalinger, 1966).

No difference was observed between the control and

the treated groups with respect to the average time

taken to cover the distance in the 20 km race but, of

the expert skiers who took part in the 30 km race, those

treated with E. senticosus extract produced signiﬁcantly

faster times than members of the placebo group. In the

biathlon, the treated group scored a signiﬁcantly higher

number of target hits in the shooting event compared

with the control group (14 vs 10, respectively). Within

the groups who had participated in the 6-day hike, those

receiving the verum claimed that they had not felt any

fatigue but had experienced a rapid restoration of

strength shortly after taking the preparation. The

restoration of pulse and arterial pressure to the initial

levels proceeded twice as rapidly (towards the end of

the ﬁrst 24 h) in the treated group compared with the

control group (delayed typically to the third day).

Tuzov (1968) conducted a placebo-controlled,

randomized, single blind comparative study of the

effects of E. senticosus, Rhodiola rosea, Rhaponticum

cartamoides and Panax ginseng on the muscular work-

ing capacities of 52 healthy athletes (aged between 18

and 24 years) who were exposed to various physical

loads. Experiments were performed either in the

absence or presence of background fatigue, and the

amount and intensity of work performed was evalu-

ated. In the ﬁrst set of experiments the study drug or

the placebo solution was administered to a subject who

then rested for 30 min before operating the bicycle in

sprint mode (maximum race speed) for 30 s. After a

5min rest the subject repeated the task, during which

time the resistance to rotation of the wheels was ad-

justed to suit the functional abilities of the athlete. The

aim of this procedure was to ensure that each subject

would be able to carry out continuous work at the

highest load intensity for a duration of 20–30 min

before exhaustion set in. The exact time taken for

each subject to reach exhaustion after working at their

appropriately chosen pace was recorded, together with

STIMULATING EFFECT OF ADAPTOGENS 835

the determined amount and intensity of work performed

during that period.

In a second series of experiments in which the sub-

jects were in a state of fatigue before measurements

were made, the drug or placebo was administered and,

rather than resting for 30 min, athletes were asked to

carry out standard dosed work for 25 min followed by

a 5 min rest before the prescribed 30 s sprints and timed

exercise began. Tests were repeated at intervals of 2–3

days, and on each occasion the subjects received 15

drops of Rhodiola rosea extract, or 2 mL of an extract

of E. senticosus, Rhaponticum cartamoides or P. ginseng,

or an equivalent volume of placebo with similar organ-

oleptic properties. The subjects had no knowledge of

the nature of the drug administered on any particular

occasion: in fact, application of adaptogens commenced

only after a period of adaptation to physical load when

the subject had got used to working on the training

equipment and the values of the intensity of muscular

work became relatively uniform. The results showed

that the efﬁcacy of the drug depended on the duration

of the physical loading and the background fatigue of

the subject. Thus, in the absence of prior fatigue,

adaptogens showed no effect on the intensity of the

sprint work. However, when the subjects were pre-

fatigued, the maximum intensity of the sprint was

increased moderately (9% vs placebo) but signiﬁcantly

(p < 0.05) by application of the extract of Rhodiola

rosea but not by the other extracts (Fig. 13a). In

contrast, under physical loading using a preset high-

intensity test, all studied adaptogens showed statistically

signiﬁcant stimulating effects (Fig. 13b) except for that

derived from P. ginseng. The best results were obtained

with the extract of R. rosea that, on pre-fatigued

subjects, gave rise to a prolongation of work by about

28% compared with the placebo (Tuzov, 1968). With

pre-fatigued athletes, improvements in the general state

and functional indices, as well as a reduction in the

recovery period, were observed in all subjects taking

herbal stimulants. Furthermore, an improvement in the

response of the blood circulation system to physical

load, presumably caused by an increase in the stroke

volume, was also observed in all athletes who had been

given the herbal stimulants. The largest improvements

in pulse rate and the highest blood pressure values

were observed in subjects who had been treated with

Rhodiola rosea. The adaptogens also showed a positive

effect on the muscular force of the back and of the hand

muscles as determined by spirometry (Tuzov, 1968).

In a recent double-blind placebo-controlled random-

ized study of the effects of acute and 4-week intake

of a standardized extract of R. rosea on the physical

capacity, muscular strength, speed of limb movement,

reaction time and attention in young volunteers, it was

demonstrated that treatment improved endurance in

exercise performance (De Bock et al., 2004). Compared

with the placebo group, acute intake of R. rosea extract

increased the time to exhaustion slightly but signiﬁc-

antly; however, daily intake of the drug for 4 weeks

produced no signiﬁcant difference compared with

placebo treatment. These results contrast with several

other studies in which signiﬁcant effects on mental and

physical performance following repeated administration

of R. rosea extract have been observed (Darbinyan

et al., 2000; Spasov et al., 2000a, b).

Very recently, a study involving a commercial, herbal-

based formula containing root of R. rosea appeared to

demonstrate that the preparation did not elicit positive

changes in cycling performance (Earnest et al., 2004).

The discrepancy of the results from this study com-

pared with the numerous other studies require explana-

tion. It might simply be that the batch of the drug

employed was not analysed prior to the experiment in

order to ensure compliance with speciﬁcation. As an

example of the necessity of such control, it should be

mentioned that in a systematic study of 25 commercial

samples of Ginseng and Eleutherococcus obtained from

a local health food store, the concentrations of active

ingredients varied by 15- and 400-fold (Harkey et al.,

2001).

Effect of adaptogens on the visual functions of eye

Increases in the peripheral sensitivity of the retina have

been reported (Galochkina, 1948) after administration

of a single dose of the air-dried powder of fruits of S.

chinensis (mixed with starch and glucose) followed by

50–60 min of adaptation to darkness. This treatment

also increased sensitivity to red light (600 nm) but de-

creased sensitivity to green light (520 nm), an outcome

that is possibly associated with a parasympathomimetic

effect of the drug.

In a related placebo-controlled study involving

healthy subjects (Trusov, 1953), the single administra-

tion of capsules containing 3 g of S. chinensis seed

powder was shown to enhance night vision and to

accelerate adaptation to darkness. For each individual,

Figure 13. The effect of stimulants on (a) the working capacity at maximal intensity for 30 s (sprint) determined 30 min after

administration, and (b) the duration of work at a preset high intensity determined 35 min after administration. (Figure drawn from

the data of Tuzov, 1968.)

836 A. PANOSSIAN AND H. WAGNER

sensitivity to light and acuity of vision, and visual ﬁeld

margins of colours were measured, respectively, 1.5 and

3h after drug administration, and the results compared

with those obtained in an initial evaluation of visual

function carried out 10–15 min before treatment. It was

clearly demonstrated that S. chinensis increased visual

acuity under low illumination and extended the visual

ﬁeld margins for white and red light by 8° to 25°. A

later extension of this work (Trusov, 1958a, b) employed

two further scales for the measurement of visual sensit-

ivity, namely, the time taken to recognize an object

in darkness, and the maximum level of darkness that

permitted such object recognition (an evaluation of

adaptation to darkness). Ninety percent of healthy sub-

jects who received a single dose (3 g) of S. chinensis

seed powder showed signiﬁcantly increased visual sensit-

ivity. Some 4.5 h after application of the adaptogen,

the time required for visual recognition of an object in

darkness had decreased from 32.3 to 18.4 s and adapta-

tion to darkness had improved markedly.

Since S. chinensis increased the rate of increase of

visual sensitivity, but not the ﬁnal level of sensitivity, it

was concluded that the adaptogen affects the neural

mechanisms of adaptation to darkness rather than

the photochemical processes in the retina of the eye

(Trusov, 1958a, b). This same study also provided

some indication of the mode of action of S. chinensis,

since pharmacological agents that mainly affect the brain

cortex are known to induce equal changes in visual

sensitivity in all regions of the visible spectrum, whilst

agents that act on the vegetative nervous system and/or

the hypothalamus–pituitary system have opposite effects

on red and green vision.

STRUCTURE–ACTIVITY RELATIONSHIP

It appears that plant adaptogens that exhibit a stimu-

lating single dose effect, namely, R. rosea, S. chinensis

and E. senticosus, all contain relatively high amounts

of phenolic compounds, particularly phenylpropane or

phenylethane derivatives. These compounds are struc-

turally related to the catecholamines, and presumably

play important roles in the SAS and CNS systems.

In contrast, plants such P. ginseng, Bryonia alba, E.

senticosus etc, which contain relatively large amounts

of tetracyclic triterpenes that are structurally similar to

corticosteroids, reveal their stress protective effects and

adaptation to stressors after repeated administration

for periods of 1–4 weeks. In these cases, the active

components play key roles in the HPA axis-mediated

regulation of the immune and neuroendocrine systems.

It is worth noting that, along with the common

feature associated with all plant adaptogens, namely,

induction of a state of non-speciﬁc resistance in stress,

these drugs exhibit various speciﬁc effects under dif-

ferent conditions. For example, it seems that the most

important effects of R. rosea extract relate to improve-

ments in mental performance, memory and learning.

On the other hand, the extract of S. chinensis shows

a hepatoprotective effect, produces an improvement

in eye vision in darkness, increases stamina, physical

performance and working capacity, particularly in tired-

ness, and is recommended for treatment of patients

presenting asternic- and astheno-depressive states.

E. senticosus exhibits a pronounced adaptogenic effect,

increasing the non-speciﬁc resistance of the organism

to viral and bacterial infections and to other harmful

stressors (radiation, cold, noise, negative emotions,

and physical load). Furthermore, a dry extract of this

adaptogen, taken at a rate of 300 mg/day for 8 weeks,

increases the quality of life of elderly patients (Cicero

et al., 2004). Chisan®, a ﬁxed combination of all three

of these plant adaptogens, has also been shown to

increase the quality of life of patients with pneumonia

when taken daily during the illness (Narimanyan et al.,

2005). In a similar manner, P. ginseng signiﬁcantly

increased the quality of life in 338 patients each taking

one capsule per day for 12 weeks compared with a

control group of 163 patients (Caso Marasco et al., 1996).

CONCLUSIONS

Only three of the known plant adaptogens, namely

R. rosea, S. chinensis and E. senticosus, exhibit a harm-

less, ‘adaptogen-type’ stimulating effect on humans

leading to improvements in mental performance and

learning efﬁcacy after single dose administration: the

most active stimulant is that derived from R. rosea. The

stimulating effects of these drugs are apparent within

30 min after administration and last for at least 4 – 6 h.

The active principles associated with the single dose

stimulating effect of the three plant adaptogens are

phenylpropane and phenylethane phenolic glycosides,

in particular, salidroside (1), rosavin (2), syringin (3)

and triandrin (4), the latter showing the strongest

activity.

REFERENCES

Aksyonova RA. 1969.

Pharmacology of Rhodioloside.

PhD Thesis

in Pharmacology. Tomsk State University, Tomsk, 1–14.

Aksenova RA, Zotova MI, Nekhoda MF, Cherdintsev SG.

1968. Comparative characteristics of the stimulating and

adaptogenic effects of

Rhodiola rosea

preparations. In

Stimulants of the Central Nervous System

, Saratikov AS

(ed.). Vol. 2. Tomsk University Press: Tomsk, 3–12.

Andrejev I, Georgijev V. 1958. Ergographic study of

Schizandra

chinensis

stimulating effect. In

The Study of Ginseng and

Schizandra chinensis in Bulgaria

, Petkov VV (ed.), Sophia,

78.

Astanin YP, Mikhelson MY, Egolinskij YA. 1943. The study of

phenamine and some other stimulants effect on sport

running.

Farmakol Toxikol

6: 60– 65.

Barnaulov OD, Limarenko AY, Kurkin VA, Zapesochnaya GG,

Shchavlinskij AN. 1986. A comparative evaluation of the

biological activity of compounds isolated from species of

Rhodiola

Khim Pharm Zh

23: 1107–1112.

Berdyshev VV. 1995. Some speciﬁc effects of single doses of

adaptogens. In

Valeology: Diagnosis, Means and Practice

in Health Care

, Breckman II (ed.). Int. Collection of Scientiﬁc

Papers, Issue 2, Vladivostok, Dalnauka, 105–117.

Bogatova RI, Malozemov VV. 1994. Experimental research on

estimation of inﬂuence of single dose of phytoadaptogens

on short memory.

The Report on ADAPT 232.

Institute of

Medical and Biological Problems (IMBP): Moscow, 1–151.

Bogatova RI, Shlyakova LV, Salnitsky VP, Wikman G. 1997.

Evaluation of the effect of single take of a phytoadaptogen

STIMULATING EFFECT OF ADAPTOGENS 837

on human subject work ability during long isolation.

Aerospace Environ Med

31(4): 51–54.

Bombardelli E, Cristoni A, Lietti A. 1980. The effect of acute and

chronic ginseng saponins treatment on adrenals function:

Biochemical and pharmacological aspects. In

Proceedings

of 3rd International Ginseng Symposium

. Korea Ginseng

Research Institute: Seoul, Korea, 9–16.

Brekhman II, Dardymov IV. 1968. New substances of plant

origin which increase non-speciﬁc resistance.

Ann Rev

Pharmacol

8: 419– 430.

Bucci LR. 2000. Selected herbals and human exercise perform-

ance.

J Clin Nutr

72 (Suppl): 624S– 636S.

Caso Marasco A, Vargas Ruiz R, Salas Villagomez A, Begona

Infante C. 1996. Double-blind study of a multivitamin com-

plex supplemented with ginseng extract.

Drugs Exp Clin

Res

22: 323– 329.

Chrousos GP, Gold PW. 1992. The concept of stress

system disorders: overview of behavioural and physical

homeostasis.

JAMA

267: 1244–1252.

Chrousos GP, McCarty R, Pacak K

et al.

1995. Stress: basic

mechanisms and clinical implications.

Ann NY Acad Sci

771: 396– 418.

Cicero AF, Derosa G, Brillante R, Bernardi R, Nascetti S,

Gaddi A. 2004. Effects of Siberian ginseng (

Eleutherococcus

senticosus

Maxim.) on elderly quality of life: a randomized

clinical trial.

Arch Gerontol Geriatr

(Suppl) 9: 69–73.

Dalinger OI. 1966. Effect of

Eleutherococcus

extract on

functional state of cardiovascular system and working

capacity of skiers. In

Stimulants of the Central Nervous

System

, Saratikov AS (ed.). Tomsk University Publishing

Press: Tomsk, 106–111.

Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G,

Wagner H. 2000.

Rhodiola rosea

in stress-induced fatigue:

a double-blind cross-over study of a standardised extract

SHR-5 with a repeated low-dose regimen on the mental

performance of healthy physicians during night duty.

Phytomedicine

7: 365– 371.

Dardymov IV. 1976.

Ginseng, Eleutherococcus. On the Mech-

anism of Biological Activity.

Nauka: Moscow.

De Bock K, Eijnde BO, Ramaekers M, Hespel P. 2004. Acute

Rhodiola

intake can improve endurance exercise perform-

ance.

Int J Sport Nutr Exerc Metab

14: 298– 307.

Earnest CP, Morss GM, Wyatt F

et al.

2004. Effect of a com-

mercial herbal-based formula on exercise performance in

cyclists.

Med Sci Sport Exerc

36: 504– 509.

Eglit NY, Zhukova VV, Kuznetsova VF, Kravchenko AN. 1965.

About the stimulating effect of

Schizandra chinensis

and its

use under physical loads. In

Materials of Scientiﬁc Meet-

ings of Khar’kov Scientiﬁc Medical Society

(Editors ?).

Zdirovya: Kiev, 829– 830.

ESCOP Monographs. 2003a. Eleutherococci radix. In

The

Scientiﬁc Foundation for Herbal Medicinal Products

, 2nd

edn. Thieme: Stuttgart, 142–149.

ESCOP Monographs. 2003b. Ginseng Radix. In

The Scientiﬁc

Foundation for Herbal Medicinal Products

, 2nd edn. Thieme:

Stuttgart, 211–222.

Fan W, Tezuka Y, Ni KM, Kadota S. 2001. Propyl-endoperoxidase

inhibitors from the underground part of

Rhodiola sacha-

linensis

Chem Pharm Bull

49: 396– 401.

Fink G. 2000.

Encyclopaedia of Stress

, Vol. 1–3. Academic Press:

San Diego.

Fulder S. 1980. The drug that builds Russians.

New Scientist

21: 83– 84.

Galochkina LN. 1948. About

Schizandra chinensis

effect on light

and color sensitivity of the eye.

Problemy Fiziologichekoy

Optiki

5: 71–73.

Grigorenko GF, Berdyshev VV. 1988. The use of tonic drinks

and drugs increasing working capacity of sailors during

night shifts.

Abstract Book of Scientiﬁc Practical Conference

on Medical and Social Aspects of the Man-Ocean Problem

118.

Ha Z, Zhu Y, Zhang X

et al.

2002. The effect of

Rhodiola

and

acetazolamide on the sleep architecture and sleep blood

oxygen saturation of persons living at 5380 meters above

sea level.

Chin J Tuberc Resp Dis

21: 1–6.

Harkey MR, Henderson GL, Gershwin ME, Stern JS, Hackman

RM. 2001. Variability in commercial ginseng products: an

analysis of 25 preparations.

Am J Clin Nutr

73: 1101–1106.

Hasan Samira MM, Attita Attita M, Allam M, Elwan O. 1985.

Effect of the standardized ginseng extract G115 on the

metabolism and electrical activity of the rabbit’s brain.

J Int

Med Res

13: 342– 348.

Kaliko IM, Tarasova AA. 1966. Effect of Leuzea and Golden

Root extracts on dynamic peculiarities of the highest neural

performance In

Stimulants of the Central Nervous System

Saratikov AS (ed.). Tomsk University Publishing Press:

Tomsk, 115–120.

Karo VI. 1945. The ergographic study of

Schizandra

stimulating

effect.

Scientiﬁc Papers of 3rd year Students of Naval Medi-

cal School, Leningrad

, Issue 3, 30– 33.

Kochmareva LI. 1958. The effect of

Schizandra chinensis

and

Ginseng on processes of concentration

Materials for the

Study of Ginseng and Schizandra

, Lazarev NV (ed.).

Issue

3. V.L. Komarov’s Far East Branch of USSR Academy of

Science: Leningrad, 12–17.

Kokhanova AN, Peresypkina NV, Balagurovskaya EN,

Kotel’nikova KM, Grigorieva IT. 1950. The effect of

Schizandra

on muscular fatigue in man. In

Proceedings of

the IV Student Scientiﬁc Session of Khabarovsk Medical

Institute, Khabarovsk

, 85– 89.

Komar VV, Kit SM, Sitschuk LV, Sitschuk VM. 1981. The effect

of Carpatian

Rhodiola rosea

on human mental activity.

Farmatsevticheskiy Zh

4: 62– 64.

Korolevich VS, Lupandin AV. 1967. The experience in using

Schizandra chinensis

seed preparation on the training of

gymnasts. In

Proceedings of Scientiﬁc Conference of the

Chair of Biological Disciplines of P.F. Lesgaft Military Phy-

sical Culture Institute on The Effect of Physical Exercises

and some other Physical Factors on the Organism Resist-

ance, Leningrad

, 166–170.

Krasik ED, Morozova ES, Petrova KP, Ragulina GA,

Shemetova LA, Shuvaev VP. 1970a. Therapy of asthenic

conditions: clinical perspectives of application of

Rhodiola

rosea

extract (golden root). In

Proceedings of Modern

Problems in Psycho-Pharmacology

, Avrutskiy GY (ed.).

Siberian Branch of Russian Academy of Sciences: Kemerovo

City, 298– 330.

Krasik ED, Petrova KP, Rogulina GA. 1970b. About the

adaptogenic and stimulating effect of

Rhodiola rosea

extract. In

Proceedings of All-union and 5th Sverdlovsk

Area Conference of Neurobiologists, Psychiatrists and

Neurosurgeons

, Avrutskiy GY (ed.). Sverdlovsk Press:

Sverdlovsk, 215– 217.

Kurkin VA, Dubishev AB, Titova IN

et al.

2003. Neurotropic

properties of some phytopreparations containing phenylpro-

panoids.

Rastit Resursi

3: 115–122.

Kurkin VA, Zapesochnaya GG. 1986. Chemical composition and

pharmacological properties of

Rhodiola rosea

Khim Pharm

Zurnal

20: 1231–1244.

Lapajev II. 1978.

Schizandra and its Curative Properties

, 3rd

amended and supplemented ed. Khabarovsk Book Press:

Khabarovsk.

Lapajev II. 1982. The effect or phytoadaptogens on working

capacity in sport divers. In

Modern Problems of Military

Medicine

Issue 2. Tomsk University Publishing: Tomsk,

170–172.

Lazarev NV. 1946. Experimental data on evaluation of Far

east Shizandra as a stimulator. In

Proceedings Scientiﬁc

Medical Council.

Vol. 5, No. 17. Military Publishing of the

Ministry of Defence of USSR: Leningrad, 62– 68.

Lazarev NV. 1962. Actual problems of the studies of the action

of adaptogens, particularly preparations of

Eleutherococcus

Symposium on

Ginseng

and

Eleutherococcus.

XX Meet-

ing on Investigations of Ginseng and other Medicinal Plants

of Far East.

DVFSO: Vladivostok, 7–14.

Lebedev AA. 1951a. Comparative evaluation of the stimulating

effect of various Schizandra products. In

Materials for

the Study of Stimulants and Tonics from Ginseng and

Schizandra Roots

, Lazarev NV (ed.). Issue 1. V.L. Komarov’s

Far East Branch of USSR Academy of Science: Vladivostok,

103–108.

Lebedev AA. 1951b. Some materials to the pharmacology

of schizandrin. In

Materials for the Study of Stimulants

and Tonics from Ginseng and Schizandra Roots

, Lazarev

NV (ed.). Issue 1. V.L. Komarov’s Far East Branch of USSR

Academy of Science: Vladivostok, 109–117.

Lebedev AA. 1955. On the pharmacology of

Schizandra

. In

Materials on Investigations of Ginseng and Shisandra

Lazarev NV (ed.), Issue 2. USSR Academy of Sciences

Publisher: Moscow, 178–188.

838 A. PANOSSIAN AND H. WAGNER

Lebedev AA. 1967.

Schizandrin – A New Stimulant from

Schizandra chinensis

Fruits.

Summary of Thesis for a

Candidate’s Degree in Medicine

Tashkent.

Lebedev AA. 1971.

Schizandra.

Meditsina

Publishing House of

USSR: Tashkent.

Levchenko KP. 1971. The experience in using

Schisandra

seed

powder during training of basketball players. In

Abstract

Book of Conference on Biologically Active Substances of

Flora and Fauna of the Far East and Paciﬁc Ocean

Vladivostok, 118.

Lupandin AV. 1990. Adaptation to natural and technogenic

extreme factors in trained and untrained adaptogen treated

individuals.

Fiziologia Cheloveka

16: 114–119.

Lupandin AV, Lapajev II. 1981.

Schizandra

. Khabarovskoye

Knizhnoye Izdatelstvo:

Khaharovsk, 1–89.

Marina TF. 1968. Effect of

Rhodiola rosea

extract on bio-

electrical activity of the cerebral cortex isolated to a dif-

ferent extent from the brain. In

Stimulants of the Central

Nervous System

, Saratikov AS (ed.). Tomsk State Univer-

sity Press: Tomsk, 27–31.

Marina TF, Alekseeva LP. 1968. Effect of

Rhodiola rosea

extract on electroencephalograms in rabbit. In

Stimulants

of the Central Nervous System

, Saratikov AS (ed.). Tomsk

State University Press: Tomsk, 22– 26.

Marina TF, Mikhaleva LK, Suslov NI. 1994. Comparative

effects of para-tyrosol and

Rhodiola

extract on the central

nervous system. In

Proceedings of a Joint Plenary Session

of Pathophysiologists and Pharmacologists of Siberia

and the Far East on Mechanisms of the Development

of Pathological Processes.

Kemerovo State University Press:

Kemerovo, 66– 68.

Medvedev MA. 1963. Effect of Ginseng and Eleutherococcus

on working parameters of radio-telegraph operators. In

Materials of Studies of Ginseng and other Medicinal Plants

of Far East

, Brekhman II, Belikov IF, Kurentsova GE (eds),

Issue 5. Primorye Publishing Press: Vladivostok, 237– 239.

Mikhailova MN. 1983. Clinical and experimental substantia-

tion of asthenic conditions therapy using

Rhodiola Rosea

extract. In

Current Problems of Psychiatry

, Goldsberg ED

(ed.). Tomsk State University Press: Tomsk, 126–127.

Murtazin IM. 1946.

Schizandra chinensis

as a stimulant under

long physical loads.

Farmakol Toxikol

9: 12–13.

Narimanian M, Badalyan M, Panosyan V

et al.

2005. Impact

of Chisan® (ADAPT-232) on the quality-of-life and its efﬁcacy

as an adjuvant in the treatment of acute non-speciﬁc

pneumonia.

Phytomedicine

(in press).

Nishibe S, Kinoshita H, Takeda H, Okano G. 1990. Phenolic

compounds from stem bark of

Acanthopanax senticosus

and their pharmacological effect in chronic swimming

stressed rats.

Chem Pharm Bull

38: 1763–1765.

Nörr H. 1993. Phytochemical and pharmacological investiga-

tions of the adaptogens:

Eleutherococcus senticosus,

Ocimum sanctum, Codonopsis pilosula, Rhodiola rosea

and

Rhodiola crenulata

. PhD Dissertation, Faculty of Chemistry

and Pharmacy, Ludwig-Maximillians University, Munich.

Panossian A. 2003. Adaptogens: Tonic herbs for fatigue and

stress.

Alt Comp Ther

9: 327–332.

Panossian A, Gabrielian E, Wagner H. 1997. Plant adaptogens

II.

Bryonia

as an adaptogen.

Phytomedicine

4: 83– 97.

Panossian A, Gabrielian E, Wagner H. 1999a. On the mechanism

of action of plant adaptogens with particular references on

cucurbitacin R diglucoside.

Phytomedicine

6: 147–155.

Panossian A, Oganessian A, Ambartsumian M, Gabrielian E,

Wagner H, Wikman G. 1999b. Effects of heavy physical

exercise and adaptogens on nitric oxide content in human

saliva.

Phytomedicine

6: 17–26.

Panossian A, Wikman G, Wagner H. 1999c. Plant adaptogens

III. Earlier and more recent aspects and concepts on their

mode of actions.

Phytomedicine

6: 287–300.

Petkov V. 1978. Effect of Ginseng on the brain biogenic

monoamines and 3′5′-AMP system. Experiments on rats.

Arzneimittelforsch

28: 338– 339.

Petkov VD, Yonkov D, Mosharoff A, Kambourova T, Alova L,

Petkov VV. 1986. Effects of alcohol aqueous extract from

Rhodiola rosea

L. roots on learning and memory.

Acta

Physiol Pharmacol Bulg

12: 3–16.

Roslyakova NA, Bogatova RI, Vezirishvili MO, Wikman G. 2000.

The effect of a single dose of Rodelim phytoadaptogen

on the performance of operators under intensive activity.

Abstract Book of Scientiﬁc Practical Conference on Bio-

logically Active Food Supplements and Natural Medicines

in the Prophylaxis, Treatment and Rehabilitation, Moscow

157–160.

Saratikov AS, Krasnov EA. 2004.

Rhodiola rosea (Golden root):

A Valuable Medicinal Plant.

Tomsk University Press: Tomsk,

1–205.

Saratikov AS, Marina TF, Kaliko IM. 1965. The stimulating effect

Rhodiola rosea

on the higher brain structures.

Newslett

Sib Branch USSR Acad Sci

8: 120–125.

Saratikov AS, Marina TF, Fisanova LL. 1978. Mechanism of action

of salidrozide on the metabolism of cerebral catecholamines.

Vopr Med Khim

5: 624– 621.

Selye H. 1950.

Stress.

Acta Medical Publisher: Montreal, 1–

127.

Shevtsov VA, Zholus BI, Shervarly VI

et al.

2003. A randomised

trial of two different doses of a SHR-5

Rhodiola rosea

ex-

tract versus placebo and control of capacity for mental work.

Phytomedicine

10: 95–105.

Sokolov SY, Boyko VP, Kurkin VA, Zapesochnaya GG,

Rvantsova NV, Grinenko HA. 1990. A comparative study of

the stimulant property of certain phenylpropanoids.

Khim

Pharm Zh

24: 66– 68.

Spasov AA, Mandrikov VB, Mironova IA. 2000a. The effect of

the preparation rhodiosin on the psychophysiological and

physical adaptation of students to an academic load.

Eksp

Klin Farmakol

63: 76–78.

Spasov AA, Wikman GK, Mandrikov VB, Mironova IA,

Neumoin VV. 2000b. A double-blind, placebo-controlled pilot

study of the stimulating and adaptogenic effect of

Rhodiola

rosea

SHR-5 extract on the fatigue of students caused by

stress during an examination period with a repeated low-

dose regimen.

Phytomedicine

7: 85– 89.

Stancheva SL, Mosharrof A. 1987. Effect of the extract of

Rhodiola rosea

L. on the content of the brain biogenic

monoamines.

Med Physiol CR Acad Bulg Sci

40: 85– 87.

Strokina TI. 1967. The changes in higher nervous activity in

neurotic patients under treatment with Eleutherococcus.

Lekastvennie Sredstva Dalnego Vostoka

7: 201–211.

Trusov MS. 1953. The effect of the far east

Schizandra chinensis

on some visual functions.

Voyenno-Medotsinskij Zh

10: 57–

62.

Trusov MS. 1958a.

Schizandra chinensis

effect on adaptation

to darkness. In

Materials for the Study of Ginseng and

Schizandra

, Lazarev NV (ed.).

Far East Branch of USSR

Academy of Science Publishing: Vladivostok, 170–176.

Trusov MS. 1958b.

The Effect of Vitamin A, Eserine and

Schizandra chinensis

on Light Sensitivity of the Visual

Organ.

Summary of Thesis for a Candidate Degree in

Medicine: Khabarovsk, 24– 29.

Tuzov SF. 1968. Comparative characteristics of the effect of

some CNS stimulants on muscular capacity on men. In

Stimulants of the Central Nervous System

, Saratikov AS

(ed.). Tomsk University Publishing Press: Tomsk, 156–161.

Vezirishvili MO, Roslyakova NA, Wikman G. 1999. The experi-

ence in developing an up-to-date biologically active supple-

ment

. Medicina Altera International Academy of Sciences

of Nature and Society Magazine

, November, 44– 46.

Viru AA. 1981.

Hormonal Mechanisms of Adaptation and

Training.

Nauka: Leningrad, 154.

Wagner H, Norr H, Winterhoff H. 1994. Plant adaptogens.

Phytomedicine

1: 63–76.

Yeﬁmova VA, Kokhanova AI, Majburd ED. 1954. On the problem

Schizandra chinensis

effect on the cerebral cortex activity.

Khabarovsk Medical Institute, Khabarovsk, Collection 13, 52–

57.

Zapesochnaya GG, Kurkin VA, Boyko VP, Kolkhir VK. 1995.

Phenylpropanoids – promising biological active compounds

of medicinal plants.

Khim Farm Zh

29: 47– 50.

Zotova MI. 1965. The effect of

Rhodiola rosea

extract on

mental working activity in man. In

Collection of Reports at

3rd Scientiﬁc Conference of Physiologists

Biochemists and

Pharmacologists of Western Siberia, Tomsk

, 298– 299.

Herbal Remedies for Mental Health Disorders: A Focus on Adaptogenic Plants and Their Mechanisms of Action

Article

May 2024

Adaptogenic plants are increasingly being recognized as potential therapeutic agents in the treatment of mental health disorders. In this review, we summarized current evidence of their efficacy, safety, and mechanisms of action in the treatment of mental health disorders. The findings of the clinical studies showed that adaptogens, such as ashwagandha, Rhodiola, and holy basil, are effective in alleviating the symptoms of stress, anxiety, and depression, with a good safety profile and minimal side effects. Adaptogenic plants exert their effects through several mechanisms of action, including modulation of the stress response systems, neuroprotection, and anti-inflammatory effects. However, challenges remain in standardizing adaptogenic plant extracts and dosage forms and in clinical studies to analyze the interactions with other pharmaceuticals. In light of these challenges, adaptogenic plants represent a promising alternative to conventional pharmacotherapy for a wide range of mental health disorders, with probable lower side effects and greater accessibility. From a clinical practice perspective, there are promising prospects for the potential of these herbal remedies in the treatment of mental health disorders for the augmentation of treatment options and for better outcomes. Further research is warranted to optimize the therapeutic regimens and to integrate these remedies into comprehensive paradigms of mental health care.

The Potential Role of Herbal Plants in the Management of Depression: Pre-Clinical and Clinical Evidence

Article

Full-text available

Oct 2024

Depression, a debilitating mental health disorder affecting millions worldwide, con-tinues to challenge the medical community. While several pharmacological interventions ex-ist, their efficacy and side effects often warrant the exploration of alternative treatments. Natu-ral products derived from plants have gained attention for their potential antidepressant prop-erties in preclinical studies. This comprehensive review examines the antidepressant activity of various plant-based extracts through preclinical investigations and explores the underlying mechanisms of action. Our review systematically analyzes the literature, encompassing a wide range of plants. We present evidence from pre-clinical and clinical studies, highlighting the behavioural and neurochemical changes induced by these plant-derived compounds. Further-more, we delve into the potential mechanisms of action, encompassing modulation of neuro-transmitters, anti-inflammatory effects, neurogenesis promotion, and antioxidant properties. The reviewed studies suggest that numerous plants possess promising antidepressant proper-ties, potentially offering novel therapeutic avenues. However, the variability in methodologies and the need for further clinical validation underscore the complexity of translating preclinical findings into effective treatments. This review serves as a valuable resource for researchers and clinicians alike, shedding light on the current state of knowledge regarding plants with an-tidepressant potential and their underlying mechanisms of action, paving the way for future investigations and therapeutic developments in the field of depression management.

Response of Sunflower (Helianthus annuus L.) to Application of Bioactive Humic Substances

Article

Full-text available

Apr 2024

Dávid Ernst

Sunflower is the second most cultivated oilseed crop in Slovakia. It remains an attractive crop in primary agricultural production because of the many benefits it provides. The study aimed to assess the impact of biological material (Subaro HTS, Sumiko HTS) and products containing bioactive substances (Humix® Universal, Humix Bór, Energen Fulhum Plus and Energen Stimul Plus) on sunflower production in the 2021–2022 growing seasons. A partial aim was to investigate the possible effect of adaptogens on a plant organism, specifically sunflower. The field trials were designed using the perpendicularly split block method with a randomized block complete design on an experimental basis of SAU in Nitra, located in a warm maize production area. The variability of weather conditions was statistically demonstrated on the achieved production parameters. Weather conditions were more favorable in 2022 regarding seed yield 3.25 ±0.31 tons per hectare (t.ha-1) and oil content 47.14 ±0.90%. Evaluation of biological material confirmed that the hybrid Sumiko HTS achieved significantly higher yields of seeds 3.29 ±0.28 t.ha-1 and oil content 46.66 ±1.32% compared to Subaro HTS. The utilization of bioactive substance combinations exhibited significant impact on sunflower production. Specifically, superior values in the examined parameters, such as seed yield 3.30 ±0.26 t.ha-1 and oil content 46.99 ±1.12%, were observed in instances where Energen Fulhum Plus + Energen Stimul Plus preparations, inclusive of adaptogens, were applied during the growth stage BBCH 18.

Botanical hybrid preparations (BHP) in phytomedicine and phytotherapy research: background and perspectives

Preprint

Full-text available

Mar 2024

Background: The commonly known assumption that combinations of several herbs in one formulation can have better efficacy due to additive or synergistic effects has not been systematically studied despite some evidence supporting the synergy concept. Study aim: The study aimed to reveal the molecular interactions in situ of host cells in response to the intervention of BHP and justify the benefits of implementing BHP in clinical practice. Results: This overview provides the results of recent clinical and network pharmacology studies of botanical herbal preparations (BHP) of Rhodiola with other plants, including Ashwagandha, Green Tea, Eleutherococcus, Schisandra, Eleutherococcus, Leuzea, Caffeine, Cordyceps, Gingko, Black Cohosh, saffron, and L-carnosine. Conclusions: The most important finding from network pharmacology studies of BHP was the evidence supporting the synergistic interaction of BHP ingredients, revealing unexpected new pharmacological activities unique and specific to the new BHP. Some studies show the superior efficacy of BHP compared with mono-drugs. At the same time, some a priori-designed combinations can fail, presumably due to antagonistic interactions and crosstalk between molecular targets within molecular networks involved in the cellular and overall response of organisms on the intervention. Network pharmacology studies help predict the results of studies to discover new indications and unpredicted adverse events.

The Milestones of Adaptogens Research and Use in Medicine

Book

Full-text available

Oct 2022

The content of this book is based on recent publications in scientific journals and on our own experience in phytotherapy. Our main aim is to summarise accumulated knowledge about the adaptogens in a simplified way, to make it easy to understand for anyone regardless of educational background. That is a challenge due to the daunting complexity of living organisms and lack of knowledge of laws of life". Cell biology is a bottomless well in complexity. However, many attempts were made to glimpse simplicity lurking within this complexity and capture this simplicity. Our book briefly introduces the adaptogenic concept based on the experience of traditional medicinal systems and recent observations from experiments on animals and studies on humans, including modern network pharmacology and systems biology approaches. The last chapter 4 of our book is apparently for advanced readers, despite the hope that it would be clear for anyone with a curious and thoughtful mind.

Adaptogens-Proven Plant Medicines

Book

Full-text available

Mar 2022

The content of this book is based on recent publications in scientific journals and on our own experience in phytotherapy. Our main aim was to summarize accumulated knowledge about the adaptogens in a simplified way, to make it easy to understand for anyone regardless of educational background. That is a challenge due to the daunting complexity of living organisms and lack of knowledge of laws of life.” Cell biology is a bottomless well in complexity. However, many attempts were made to glimpse simplicity lurking within this complexity and capture this simlicity. Our book briefly introduces the adaptogenic concept based on the experience of traditional medicinal systems and recent observations from experiments on animals and studies on humans, including modern network pharmacology and systems biology approaches. The last chapter of our book is apparently for advanced readers, despite the hope that it would be clear for anyone with a curious and thoughtful mind.

Integrative and Complementary Medicine in Psychiatry

Chapter

Sep 2024

The role and mechanism of AMPK in pulmonary hypertension

Article

Full-text available

Aug 2024
Ther Adv Respir Dis

Pulmonary hypertension (PH) is a chronic progressive disease with high mortality. There has been more and more research focusing on the role of AMPK in PH. AMPK consists of three subunits—α, β, and γ. The crosstalk among these subunits ultimately leads to a delicate balance to affect PH, which results in conflicting conclusions about the role of AMPK in PH. It is still unclear how these subunits interfere with each other and achieve balance to improve or deteriorate PH. Several signaling pathways are related to AMPK in the treatment of PH, including AMPK/eNOS/NO pathway, Nox4/mTORC2/AMPK pathway, AMPK/BMP/Smad pathway, and SIRT3-AMPK pathway. Among these pathways, the role and mechanism of AMPK/eNOS/NO and Nox4/mTORC2/AMPK pathways are clearer than others, while the SIRT3-AMPK pathway remains still unclear in the treatment of PH. There are drugs targeting AMPK to improve PH, such as metformin (MET), MET combination, and rhodiola extract. In addition, several novel factors target AMPK for improving PH, such as ADAMTS8, TUFM, and Salt-inducible kinases. However, more researches are needed to explore the specific AMPK signaling pathways involved in these novel factors in the future. In conclusion, AMPK plays an important role in PH.

Sugarcane (Saccharum officinarum L.) induces psychostimulant, anxiolytic-like effects and improvement of motor performance in rats

Article

Jun 2024
J ETHNOPHARMACOL

Rhodiola rosea: a review in the context of PPPM approach

Article

May 2024

A natural “medicine and food” plant, Rhodiola rosea (RR) is primarily made up of organic acids, phenolic compounds, sterols, glycosides, vitamins, lipids, proteins, amino acids, trace elements, and other physiologically active substances. In vitro, non-clinical and clinical studies confirmed that it exerts anti-inflammatory, antioxidant, and immune regulatory effects, balances the gut microbiota, and alleviates vascular circulatory disorders. RR can prolong life and has great application potential in preventing and treating suboptimal health, non-communicable diseases, and COVID-19. This narrative review discusses the effects of RR in preventing organ damage (such as the liver, lung, heart, brain, kidneys, intestines, and blood vessels) in non-communicable diseases from the perspective of predictive, preventive, and personalised medicine (PPPM/3PM). In conclusion, as an adaptogen, RR can provide personalised health strategies to improve the quality of life and overall health status.