Rhodiola rosea: A Possible Plant Adaptogen

Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001 Page 293

Rhodiola rosea:

A Possible Plant Adaptogen

Gregory S. Kelly, ND

Introduction

Rhodiola rosea (“golden root” or “Arctic root”) is widely distributed at high altitudes in

Arctic and mountainous regions throughout Europe and Asia. It is a popular plant in traditional

medical systems in Eastern Europe and Asia, with a reputation for stimulating the nervous

system, decreasing depression, enhancing work performance, eliminating fatigue, and prevent-

ing high altitude sickness.

In addition to Rhodiola rosea, over 200 different species of Rhodiola

have been identified and at least 20 are used in traditional medical systems in Asia, including R.

alterna, R. brevipetiolata, R. crenulata, R. kirilowii, R. quadrifida, R. sachalinensis, and R.

sacra.

Rhodiola rosea has been intensively studied in Russia and Scandinavia for more than 35

years. Although the majority of this research on Rhodiola rosea is unavailable for review, avail-

able literature is supportive of its adaptogenic properties. Similar to other plant adaptogens

investigated by Russian researchers, such as Eleutherococcus senticosus (Siberian ginseng) and

Panax ginseng (Korean ginseng), extracts of this plant produce favorable changes in a variety of

diverse areas of physiological function, including neurotransmitter levels, central nervous sys-

tem activity, and cardiovascular function.

Abstract

Rhodiola rosea

is a popular plant in traditional medical systems in Eastern Europe and

Asia with a reputation for stimulating the nervous system, decreasing depression,

enhancing work performance, eliminating fatigue, and preventing high altitude sickness.

Rhodiola rosea

has been categorized as an adaptogen by Russian researchers due to

its observed ability to increase resistance to a variety of chemical, biological, and physical

stressors. Its claimed benefits include antidepressant, anticancer, cardioprotective, and

central nervous system enhancement. Research also indicates great utility in asthenic

conditions (decline in work performance, sleep difficulties, poor appetite, irritability,

hypertension, headaches, and fatigue) developing subsequent to intense physical or

intellectual strain. The adaptogenic, cardiopulmonary protective, and central nervous

system activities of

Rhodiola rosea

have been attributed primarily to its ability to influence

levels and activity of monoamines and opioid peptides such as beta-endorphins.

(

Altern Med Rev

2001;6(3):293-302)

Gregory S. Kelly, ND –Associate Editor, Alternative Medicine Review; Correspondence address: 179 Dwight St Apt 303,

New Haven, CT 06511. E-mail: [email protected]

Page 294 Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001

Rhodiola rosea has been categorized

as an adaptogen by Russian researchers due

to its observed ability to increase resistance to

a variety of chemical, biological, and physi-

cal stressors. Origination of the term adaptogen

has been dated to 1947 and credited to a Rus-

sian scientist, Lazarev. He defined an

“adaptogen” as an agent that allows an organ-

ism to counteract adverse physical, chemical,

or biological stressors by generating non-spe-

cific resistance. Inherent in his definition is the

concept that administration of the adaptogenic

agent allows an organism to pre-adapt itself

in a manner that allows it to be more capable

of responding appropriately when diverse de-

mands are eventually placed on it. In 1969,

Brekhman and Dardymov proposed specific

criteria that need to be fulfilled in order for a

substance to qualify as an adaptogen

(Table 1).

Subjecting animals and humans to a

period of stress produces characteristic

changes in several hormones and parameters

associated with the central nervous system and

the hypothalamic-pituitary-adrenal axis

(HPA). HPA changes include an increase in

cortisol, a reduced sensitivity of the HPA to

feedback down-regulation, and a disruption in

the circadian rhythm of cortisol secretion.

Central nervous system changes include the

stress-induced depletion of catecholamine neu-

rotransmitters such as norepinephrine and

dopamine. An acute increase in beta-endorphin

levels is also observed under stressful condi-

tions.

To successfully combat stress and

stressful situations, adaptation is required.

Adaptation might be best thought of as the

ability to be exposed to a stressor, while re-

sponding with either decreased or no charac-

teristic hormonal perturbations. Adaptation

also implies being prepared to and capable of

rapidly reassuming homeostasis after the stres-

sor is withdrawn. As an example, a well-trained

athlete can participate in an event that would

induce a large HPA perturbation (stress re-

sponse) in a sedentary person, and yet the ath-

lete will be relatively unaffected. This is a re-

sult of adaptation that has occurred during the

athlete’s training process. Additionally, if ath-

letes are exposed to stressors they were not

trained for, hormonal perturbations character-

istic of a stress response would be expected;

however, this response might not be as great

as that found in less fit individuals. Further-

more, after the stress ended, their physiology

1. An adaptogen produces a non-specific response in an organism; i.e., an increase

in power of resistance against multiple stressors including physical, chemical, or

biological agents.

2. An adaptogen has a normalizing influence on physiology, irrespective of the

direction of change from physiological norms caused by the stressor.

3. An adaptogen is incapable of influencing normal body functions more than

required to gain non-specific resistance

Rhodiola rosea is considered by Russian researchers to satisfy all three criteria.

Table 1. Criteria for Defining an Adaptogen

Rhodiola rosea

Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001 Page 295

would be expected to re-establish homeosta-

sis rapidly. This is a result of non-specific re-

sistance to stress gained by virtue of a train-

ing-induced higher level of fitness.

The utility of plant adaptogens is

analogous to the training an athlete undergoes

in order to prepare for competition. Plant

adaptogens cause our physiology to begin the

adaptation process to stress. When a stressful

situation occurs, consuming adaptogens gen-

erates a degree of generalized adaptation (or

non-specific resistance) that allows our physi-

ology to handle the stressful situation in a more

resourceful manner.

As an example of this process,

Rhodiola rosea administration promotes a

moderate increase in the amount of serum

immunoreactive beta-endorphin in rats under

basal conditions. This moderate increase is

similar to that found when rats are adapted to

exercise. When Rhodiola rosea-treated rats

were subjected to a 4-hour period of non-spe-

cific stress, the expected elevation in beta-en-

dorphin was either not observed or substan-

tially decreased. Consequently, the character-

istic perturbations of the HPA were decreased

or totally prevented.

In these rats administra-

tion of Rhodiola rosea appears to have gener-

ated non-specific resistance and prepared the

rats to respond more appropriately to the even-

tual stressful situation.

Chemical Composition

The chemical composition and physi-

ological properties of Rhodiola species are to

a degree species-dependent, although some

overlap in constituents and physiological prop-

erties does exist in many Rhodiola species.

Twenty-eight compounds have been

isolated from the roots and above-ground parts

of Rhodiola rosea, including 12 novel

compounds. The roots contain a range of

biologically active substances including

organic acids, flavonoids, tannins, and

phenolic glycosides. The stimulating and

adaptogenic properties of Rhodiola rosea were

originally attributed to two compounds

isolated from its roots, identified as p-tyrosol

and the phenolic glycoside rhodioloside.

Rhodioloside was later determined to be

structurally similar to the known glycoside

salidroside found in several other plant species.

Salidroside, rhodioloside, and occasionally

rhodosin are used to describe this compound

and are considered to be synonyms. Additional

glycoside compounds isolated from the root

include rhodioniside, rhodiolin, rosin, rosavin,

rosarin, and rosiridin. These glycoside

compounds are also thought to be critical for

the plant’s observed adaptogenic properties.

1,4

A range of antioxidant compounds

have been identified in Rhodiola rosea and

related species, including p-tyrosol, organic

acids (gallic acid, caffeic acid, and chlorogenic

acid), and flavonoids (catechins and

proanthocyanidins).

5,6

Significant free-radical

scavenging activity has been demonstrated for

alcohol and water extracts of Rhodiola sp. and

is attributed to the variety of antioxidant com-

pounds.

5,6

p-Tyrosol has been shown to be

readily and dose-dependently absorbed after

an oral dose,

7,8

and appears to produce a sig-

nificant antioxidant

and modest 5-

lipoxygenase inhibitory activity

in vivo.

Salidroside (rhodioloside), the addi-

tional salidroside-like glycoside compounds

(rhodiolin, rosin, rosavin, rosarin, and

rosiridin), and p-tyrosol are thought to be the

most critical plant constituents needed for

therapeutic activity.

1,2

The contents of

salidroside and p-tyrosol in root samples gath-

ered from various areas in China have been

shown to range from 1.3-11.1 mg/g and 0.3-

2.2 mg/g, respectively.

These two compounds

have been found in all studied species of

Rhodiola; however, the other active glycosides,

including rosavin, rosin, and rosarin, have not

been found in all examined Rhodiola species.

5,6

Because of this variation within the Rhodiola

genus, verification of Rhodiola rosea by high

performance liquid chromatography (HPLC)

is dependent on the content of the additional

Page 296 Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001

glycosides (rather than salidroside and

p-tyrosol); rosavin (Figure 1) is the constitu-

ent currently selected for standardization of

extracts.

Proposed Mechanisms of Action

The adaptogenic properties, cardio-

pulmonary protective effects, and central ner-

vous system activities of Rhodiola rosea have

been attributed primarily to its ability to influ-

ence levels and activity of monoamines and

opioid peptides such as beta-endorphins.

Oral administration of a water extract

of Rhodiola rosea to rats for 10 days modu-

lated biogenic monoamines in the cerebral

cortex, brain stem, and hypothalamus. In the

cerebral cortex and brain stem, levels of nor-

epinephrine and dopamine decreased, while

the amount of serotonin increased substan-

tially. In the hypothalamus, the results were

reversed with a 3-fold increase in the amount

of norepinephrine and dopamine, and a trend

toward reduced serotonin levels. It is believed

these changes in monoamine levels are a re-

sult of Rhodiola rosea inhibiting the activity

of the enzymes responsible for monoamine

degradation, monoamine oxidase and cat-

echol-O-methyltransferase. It is also believed

Rhodiola rosea facilitates the transport of neu-

rotransmitters within the brain.

In addition

to these central effects on monoamines,

Rhodiola rosea has been reported to prevent

both catecholamine release and subsequent

cAMP elevation in the myocardium, and the

depletion of adrenal catecholamines induced

by acute stress.

Abstracts of untranslated Russian re-

search indicate that a great deal of the activity

of Rhodiola rosea might be secondary to an

ability to induce opioid peptide biosynthesis

and through the activation of both central and

peripheral opioid receptors.

3,13-15

Lack of cur-

rent availability of the complete text of these

articles make verification of these effects im-

possible.

Experimental Studies

Adaptogenic Activity

Rhodiola rosea appears to offer gen-

eralized resistance against physical, chemical,

and biological stressors in rats and other ani-

mals studied. Evidence also suggests

cardioprotective and anticancer benefits in

animals.

In the test of swimming “to the limit,”

Rhodiola rosea administration increased the

swimming time of rats 135-159 percent. Work-

ing capacity of the rats consistently improved

throughout the supplementation period.

Figure 1. Structure of Rosavin

Rosavin

Rhodiola rosea

Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001 Page 297

Eggs from the freshwater snail Lym-

naea stagnalis were incubated in water extracts

of Rhodiola rosea and subsequently exposed

to a variety of environmental stressors, includ-

ing heat shock (43°C for four minutes), oxi-

dative stress (600 µM menadione for two

hours), and heavy metal-induced stress (one-

hour exposure to 150 µM copper sulphate or

20 µM cadmium chloride). Exposure to these

environmental stressors kills 80-90 percent of

larvae within four days post-exposure. Pre-in-

cubation with Rhodiola rosea extract afforded

a significant degree of non-specific resistance

against each of these environmental stressors

as measured by rate of survival. While only

nine percent of the control population survived

exposure to heat shock, approximately 90 per-

cent of snail larvae pre-incubated with

Rhodiola rosea (40.5 µg/ml) survived. Pre-in-

cubation with Rhodiola resulted in non-spe-

cific resistance to oxidative stress (survival of

approximately 68 percent) and heavy metal

stress (approximately 28-35 percent of larvae

survived depending on the metal exposure).

Two experiments have suggested pos-

sible benefit on various aspects of learning and

memory in rats under certain experimental

conditions. Rhodiola rosea extract adminis-

tered orally at a dose of 0.1 mL/day for 10

days resulted in a non-significant trend toward

protection against impairments in memory, as

assessed by step-down passive avoidance, in-

duced by electroshock in rats.

Rhodiola rosea

extract was administered in a single dose of

0.10 mL. Improvements in both learning and

memory retention, as determined by using a

maze test with negative reinforcement, were

observed. Repeated dosing with the same

quantity of the extract over a 10-day period

generated significant improvement in long-

term memory as assessed by the maze test with

negative enforcement and the “staircase”

method with positive enforcement. However,

in this experiment two other doses were tested

(0.02 and 1.0 mL) and were found to have no

substantial effect on learning and memory.

This suggests the possibility of an efficacious

dose of Rhodiola rosea administration, above

and below which beneficial physiological ef-

fects might be less likely. In the other experi-

mental conditions investigated (active avoid-

ance with negative reinforcement using a

“shuttle box” and passive avoidance using

“step down” and “step through”) no benefi-

cial effects on either learning or memory were

observed with any of the administered doses

of Rhodiola rosea.

Cardioprotective Activity

Rhodiola rosea has been shown to

moderate against stress-induced damage and

dysfunction in cardiovascular tissue. Treat-

ment with Rhodiola rosea extract prevents the

decrease in cardiac contractile force second-

ary to environmental stress in the form of acute

cooling and contributes to stable contractility.

In animals, acute cooling leads to a decrease

in myocardial contractile activity that partially

recovers during the first 18 hours after the cold-

stress is removed. This recovery is viewed as

only partial, since the heart tissue is incapable

of stable contractility during perfusion. Pre-

treatment with Rhodiola rosea extracts appears

to create a beneficial adaptive response in this

type of stress. When Rhodiola pretreated rats

were exposed to acute cooling, the decrease

in contractility was prevented and stable con-

tractility of heart tissue occurred during per-

fusion.

Other reports suggest administration of

Rhodiola rosea protects cardiovascular tissue

from stress-induced catecholamine release

and mitigates against adrenaline-induced

arrhythmias in rats.

13,14,19

The antiarrhythmic

effect of Rhodiola rosea is suggested to be

secondary to an ability to induce opioid pep-

tide biosynthesis

and related to the stimula-

tion of peripheral kappa-opioid receptors.

Page 298 Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001

Anticancer Activity

Administration of Rhodiola rosea ap-

pears to have potential as an anticancer agent,

and might be useful in conjunction with some

pharmaceutical antitumor agents. In rats with

transplanted solid Ehrlich adenocarcinoma and

metastasizing rat Pliss lymphosarcoma,

supplementation with Rhodiola rosea extract

inhibited the growth of both tumor types, de-

creased metastasis to the liver, and extended

survival times.

Administration of Rhodiola

rosea extract also directly suppressed the

growth of and the extent of metastasis from

transplanted Lewis lung carcinomas.

When

Rhodiola rosea extract was combined with the

antitumor agent cyclophosphamide in these

same tumor models, the antitumor and

antimetastatic efficacy of drug treatment was

enhanced. The authors also commented that,

“complete abrogation of the haematotoxicity

of cyclophosphamide” was observed.

The

chemotherapeutic drug Adriamycin is known

to induce pronounced liver dysfunction, gen-

erally reflected by an increase in transaminase

levels. In animal experiments, adding Rhodiola

rosea extract to a protocol with Adriamycin

resulted in an improved inhibition of tumor

dissemination (as compared to that found with

Adriamycin alone), and the combined proto-

col prevented liver toxicity.

Clinical Studies

Although Rhodiola rosea has been

studied in the former Soviet Union for more

than 35 years, this research is presently un-

available for review. This makes it impossible

to verify the Russian claims of its antidepres-

sant, anticancer, cardioprotective, and central

nervous system enhancing properties.

Avail-

able animal evidence seems supportive of a

possible role for this plant adaptogen in many

of these conditions. Table 2 outlines the con-

ditions suggested to benefit from Rhodiola

supplementation.

There have also been claims that this

plant has great utility as a therapy in asthenic

conditions (decline in work performance, sleep

disturbances, poor appetite, irritability, hyper-

tension, headaches, and fatigue) developing

subsequent to intense physical or intellectual

strain, influenza and other viral exposures, and

other illness.

Two randomized, double-blind,

placebo-controlled trials of the standardized

extract of Rhodiola rosea root (SHR-5) pro-

vide a degree of support for these claimed

adaptogenic properties and indicate possible

utility in asthenic conditions induced by over-

work or over study. SHR-5 is standardized to

contain rosavin (3.6%), salidroside (1.6%), and

p-tyrosol (<0.1%).

Table 2. Conditions Suggested to Benefit from Rhodiola rosea

Supplementation

Amenorrhea Depression Insomnia

Asthenia Fatigue Periodontal Disease

(topical)

Cancer Headaches Schizophrenia

Colds Hypertension Sexual Dysfunction

and Flus (males)

Rhodiola rosea

Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001 Page 299

Darbinyan et al evaluated the effect of

chronic administration of 170 mg of SHR-5

for 14 days on aspects of mental performance

and fatigue on 56 healthy male and female

physicians (age 24-35) on night duty. Mental

performance was evaluated using tests to de-

termine speed of visual and auditory percep-

tion, attention capacity, and short-term

memory. Based on the results of the battery of

tests used, a Fatigue Index was calculated. The

trial was divided into three periods: (1) a two-

week test period of one SHR-5 or placebo tab-

let daily; (2) a two-week washout period; and

(3) a third two-week cross-over period of one

placebo or SHR-5 tablet daily. A statistically

significant improvement in Fatigue Index was

observed during the first two-week period in

the SHR-5 group, and the improved mental

performance reverted toward baseline values

during the washout period. Administration of

SHR-5 for the final two weeks of the six-week

night duty period was unable to significantly

offset declines in mental performance.

Spasov et al investigated the effects of

SHR-5 on male medical students during an

exam period. Forty students were randomized

to receive either 50 mg SHR-5 or placebo twice

daily for a period of 20 days. The students re-

ceiving the standardized extract of Rhodiola

rosea demonstrated significant improvements

in physical fitness, psychomotor function,

mental performance, and general wellbeing.

Subjects receiving the Rhodiola rosea extract

also reported statistically significant reductions

in mental fatigue, improved sleep patterns, a

reduced need for sleep, greater mood stabil-

ity, and a greater motivation to study. The av-

erage exam scores between students receiv-

ing the Rhodiola rosea extract and placebo

were 3.47 and 3.20, respectively.

Dosage and Toxicity

In the two double-blind clinical trials,

the dose of a standardized Rhodiola rosea ex-

tract ranged from 100-170 mg per day. The

content of rosavin consumed in these daily

doses is approximately 3.6-6.14 mg. The thera-

peutic dose of available Rhodiola rosea prepa-

rations will vary depending on degree of stan-

dardization; however, for chronic administra-

tion rosavin content within the above range

seems prudent. This would suggest a dose of

approximately 360-600 mg Rhodiola rosea

daily of an extract standardized for one-per-

cent rosavin, 180-300 mg of an extract stan-

dardized for two-percent rosavin, or the dose

of between 100-170 mg for an extract stan-

dardized for 3.6-percent rosavin. As an

adaptogen, chronic administration is normally

begun several weeks prior to a period of ex-

pected increased physiological, chemical, or

biological strain, and continued throughout the

duration of the challenging event or activity.

When using Rhodiola rosea as a single dose

for acute purposes (e.g., for an exam or ath-

letic competition), the suggested dose is three

times the dose used for chronic supplementa-

tion.

The Russian approach to long-term

supplementation with adaptogens generally

calls for repeating cycles characterized by

short periods of adaptogen administration, fol-

lowed by an interval with no supplementa-

tion.

Rhodiola rosea has been administered

for periods ranging from as little as one day

(acute administration) up to four months. Un-

til more specific information is available, a

dosing regime following the established pat-

terns used with other plant adaptogens, with

periodic intervals of abstinence, seems war-

ranted when Rhodiola rosea is being used

chronically.

At the doses administered in the clini-

cal trials, a complete absence of all side ef-

fects has been reported. However, preliminary

clinical feedback indicates that at doses of 1.5-

2.0 grams and above of Rhodiola rosea ex-

tract standardized for two-percent rosavin,

some individuals might experience an increase

in irritability and insomnia within several days.

It is possible that other physiological param-

eters that benefit from a lower dose of Rhodiola

Page 300 Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001

rosea extract might be exacerbated by a dose

that is inappropriately high and/or sustained

for prolonged periods of time.

Evidence on the safety and appropri-

ateness of Rhodiola rosea supplementation

during pregnancy and lactation is currently

unavailable.

Conclusion

Consistent with benefits found with

other adaptogenic substances, Rhodiola rosea

appears to offer generalized resistance to

physical, chemical, and biological stressors.

Available evidence suggests it can be a suit-

able substitute in conditions where other

adaptogens might be considered. However,

Rhodiola rosea also appears to be unique

among the currently available adaptogenic

herbs and might offer an advantage in some

clinical conditions and stressful circumstances.

Unlike Korean and Siberian ginseng, which

are thought to exert their adaptogenic activity

primarily at the level of HPA function,

27-29

Rhodiola rosea appears to exert its adaptogenic

effects by working centrally and peripherally

on monoamine and opioid synthesis, transport,

and receptor activity. If this is in fact the case

in humans, it suggests the potential for thera-

peutic utility of Rhodiola rosea in conditions

not particularly responsive to administration

of ginseng products. It also suggests the pos-

sibility of potential synergistic interactions

among Rhodiola rosea and other plant

adaptogens.

Based on the proposed mechanism of

action and available experimental data,

Rhodiola rosea appears to offer an advantage

over other adaptogens in circumstances of

acute stress. A single dose of Rhodiola rosea

prior to acute stress produces favorable results

and prevents stress-induced disruptions in

function and performance. Acute stress tends

to initially impact monoamine levels and en-

dorphins, while chronic stress places greater

demands on the HPA axis. While this is a gen-

eralization and there is obvious overlap in the

stress response, Rhodiola does seem to exert a

pronounced effect on aspects of the acute stress

response. Since many stressful situations are

acute in nature, and sometimes unexpected, an

adaptogen that can be taken acutely in these

circumstances, rather than requiring chronic

advance supplementation, could be very use-

ful.

Rhodiola rosea also offers some

cardioprotective benefits not associated with

other adaptogens. Its proposed ability to mod-

erate stress-induced damage and dysfunction

in cardiovascular tissue might make Rhodiola

rosea the adaptogen of choice among patients

at higher risk for cardiovascular disease.

Since Rhodiola rosea administration

appears to impact central monoamine levels,

it might also provide benefits and be the

adaptogen of choice in clinical conditions char-

acterized by an imbalance of central nervous

system monoamines. This is consistent with

Russian claims for improvements in depres-

sion and schizophrenia. It also suggests that

research in areas such as seasonal affective

disorder, fibromyalgia, and chronic fatigue

syndrome, to name a few clinical conditions,

is warranted.

Administration of Rhodiola rosea ap-

pears to have potential as an anticancer agent,

and might be useful in conjunction with some

pharmaceutical antitumor agents. While avail-

able evidence is limited to animal models, re-

sults appear promising. This is an area that

would benefit from additional research.

The clearest indication for Rhodiola

rosea administration is for the asthenic condi-

tion resulting from acute or chronic overwork,

which may manifest as decline in work per-

formance, sleep disturbances, poor appetite,

irritability, hypertension, headaches, and fa-

tigue.

Some animal and preliminary clinical

evidence suggests the need for a narrow range

of therapeutic dosage of Rhodiola rosea, above

and below which beneficial physiological ef-

fects might be less likely. Because of this, it

Rhodiola rosea

Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001 Page 301

seems prudent to keep doses at a moderate

level both in terms of the quantity and dura-

tion of supplementation. While Rhodiola rosea

appears to be a promising plant medicine, and

has been investigated intensively in Russia,

additional research is required before any con-

clusions with respect to its therapeutic utility

can be made.

References

1. Petkov VD, Yonkov D, Mosharoff A, et al.

Effects of alcohol aqueous extract from

Rhodiola rosea L. roots on learning and

memory. Acta Physiol Pharmacol Bulg

1986;12:3-16.

2. Brekhman II, Dardymov IV. New substances

of plant origin which increase nonspecific

resistance. Ann Rev Pharmacol 1969;9:419-

430.

3. Lishmanov IB, Trifonova ZV, Tsibin AN, et al.

Plasma beta-endorphin and stress hormones in

stress and adaptation. Biull Eksp Biol Med

1987;103:422-424. [Article in Russian]

4. Linh PT, Kim YH, Hong SP, et al. Quantitative

determination of salidroside and tyrosol from

the underground part of Rhodiola rosea by

high performance liquid chromatography. Arch

Pharm Res 2000;23:349-352.

5. Lee MW, Lee YA, Park HM, et al.

Antioxidative phenolic compounds from the

roots of Rhodiola sachalinensis A. Bor. Arch

Pharm Res 2000;23:455-458.

6. Ohsugi M, Fan W, Hase K, et al. Active-

oxygen scavenging activity of traditional

nourishing-tonic herbal medicines and active

constituents of Rhodiola sacra. J

Ethnopharmacol 1999;67:111-119.

7. Visioli F, Galli C, Bornet F, et al. Olive oil

phenolics are dose-dependently absorbed in

humans. FEBS Lett 2000;468:159-160.

8. Bonanome A, Pagnan A, Caruso D, et al.

Evidence of postprandial absorption of olive

oil phenols in humans. Nutr Metab Cardiovasc

Dis 2000;10:111-120.

9. de la Puerta R, Ruiz Gutierrez V, Hoult JR.

Inhibition of leukocyte 5-lipoxygenase by

phenolics from virgin olive oil. Biochem

Pharmacol 1999;57:445-449.

10. Boon-Niermeijer EK, van den Berg A,

Wikman G, Wiegant FA. Phyto-adaptogens

protect against environmental stress-induced

death of embryos from the freshwater snail

Lymnaea stagnalis. Phytomedicine

2000;7:389-399.

11. Stancheva SL, Mosharrof A. Effect of the

extract of Rhodiola rosea L. on the content of

the brain biogenic monamines. Med Physiol

1987;40:85-87.

12. Maslova LV, Kondrat’ev BI, Maslov LN,

Lishmanov IB. The cardioprotective and

antiadrenergic activity of an extract of

Rhodiola rosea in stress. Eksp Klin Farmakol

1994;57:61-63. [Article in Russian]

13. Lishmanov IB, Maslova LV, Maslov LN,

Dan’shina EN. The anti-arrhythmia effect of

Rhodiola rosea and its possible mechanism.

Biull Eksp Biol Med 1993;116:175-176.

[Article in Russian]

14. Maimeskulova LA, Maslov LN, Lishmanov

IB, Krasnov EA. The participation of the mu-,

delta- and kappa-opioid receptors in the

realization of the anti-arrhythmia effect of

Rhodiola rosea. Eksp Klin Farmakol

1997;60:38-39. [Article in Russian]

15. Lishmanov IB, Naumova AV, Afanas’ev SA,

Maslov LN. Contribution of the opioid system

to realization of inotropic effects of Rhodiola

rosea extracts in ischemic and reperfusion

heart damage in vitro. Eksp Klin Farmakol

1997;60:34-36. [Article in Russian]

16. Azizov AP, Seifulla RD. The effect of elton,

leveton, fitoton and adapton on the work

capacity of experimental animals. Eksp Klin

Farmakol 1998;61:61-63. [Article in Russian]

17. Lazarova MB, Petkov VD, Markovska VL, et

al. Effects of meclofenoxate and Extr.

Rhodiolae roseae L. on electroconvulsive

shock-impaired learning and memory in rats.

Methods Find Exp Clin Pharmacol

1986;8:547-552.

18. Afanas’ev SA, Alekseeva ED, Bardamova IB,

et al. Cardiac contractile function following

acute cooling of the body and the adaptogenic

correction of its disorders. Biull Eksp Biol Med

1993;116:480-483. [Article in Russian]

19. Maimeskulova LA, Maslov LN. The anti-

arrhythmia action of an extract of Rhodiola

rosea and of n-tyrosol in models of experimen-

tal arrhythmias. Eksp Klin Farmakol

1998;61:37-40. [Article in Russian]

Page 302 Alternative Medicine Review

◆ Volume 6, Number 3 ◆ 2001

20. Udintsev SN, Shakhov VP. The role of

humoral factors of regenerating liver in the

development of experimental tumors and the

effect of Rhodiola rosea extract on this

process. Neoplasma 1991;38:323-331.

21. Udintsev SN, Schakhov VP. Decrease of

cyclophosphamide haematotoxicity by

Rhodiola rosea root extract in mice with

Ehrlich and Lewis transplantable tumors. Eur J

Cancer 1991;27:1182.

22. Udintsev SN, Krylova SG, Fomina TI. The

enhancement of the efficacy of adriamycin by

using hepatoprotectors of plant origin in

metastases of Ehrlich’s adenocarcinoma to the

liver in mice. Vopr Onkol 1992;38:1217-1222.

[Article in Russian]

23. Germano C, Ramazanov Z, Bernal Suarez M.

Arctic Root (Rhodiola Rosea): The Powerful

New Ginseng Alternative. New York, NY:

Kensington Publishing Corp; 1999.

24. Darbinyan V, Kteyan A, Panossian A, et al.

Rhodiola rosea in stress induced fatigue – a

double blind cross-over study of a standardized

extract SHR-5 with a repeated low-dose

regimen on the mental performance of healthy

physicians during night duty. Phytomedicine

2000;7:365-371.

25. Spasov AA, Wikman GK, Mandrikov VB, et

al. 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 exami-

nation period with a repeated low-dose

regimen. Phytomedicine 2000;7:85-89.

26. Baranov AI. Medicinal uses of ginseng and

related plants in the Soviet Union: recent

trends in the Soviet literature. J

Ethnopharmacol 1982;6:339-353.

27. Hiai S, Yokoyama H, Oura H, Yano S. Stimula-

tion of pituitary-adrenocortical system by

ginseng saponin. Endocrinol Jpn 1979;26:661-

665.

28. Fulder SJ. Ginseng and the hypothalamic-

pituitary control of stress. Am J Chin Med

1981;9:112-118.

29. Golotin VG, Gonenko VA, Zimina VV, et al.

Effect of ionol and eleutherococcus on changes

of the hypophyseo-adrenal system in rats under

extreme conditions. Vopr Med Khim

1989;35:35-37. [Article in Russian]