Eleutherococcus senticosus: Studies and effects *

Abstract

Ginseng is one of the most popular herbal sup-plements in the world. It is a plant widely used in folk and traditional medicines for cardiovascular, immune, nervous and endocrine systems, and according to the researchers, it has the ability to increase the non-specific resistance state, which characterizes it as an adaptogenic substance. There are different species of ginseng, such as the American, Chinese, Korean and Japanese ginseng; the Korean species (Panax ginseng) is being used for thousands of years as a tonic, prophylactic and "restorative" agent, with power-ful antioxidant properties. For a long time, its use was empirical, because people used to beli-eve that it was a panacea that promoted longe-vity, with beneficial effects for the treatment of physical fatigues. Nowadays, the active compo-nents of Eleutherococcus senticosus are well described, however, there are no data on the quantity of a certain class of these secondary compounds produced in each species. Although the Eleutherococcus senticosus extract may con-tain several substances, including vitamins, mi-nerals, cellulose, and ethanol, the substances responsible for inducing various physiological responses are the eleutherosides (in the root) and ciwujianosides (in the leaf). As Eleutheroco-ccus senticosus receives great attention by show-ing that its active components can provide protec-tion against oxidative stress, among other bene-fits, contributing to health and the prevention and treatment of diseases, such as diabetes, can-cer, cardiovascular disease and inflammation. The purpose of this article is to describe the main, adverse and toxicological effects of Eleuthero-coccus senticosus recently related in the litera-ture.

Full text

Vol.5, No.9, 1509-1515 (2013) Health
http://dx.doi.org/10.4236/health.2013.59205
Eleutherococcus senticosus: Studies and effects*
Aline Arouca, Dora Maria Grassi-Kassisse#
Department of Structural and Functional Biology, Laboratory of Stress Study, Institute of Biology, University of Campinas,
Campinas, Brazil; #Corresponding Author: doramgk@unicamp.br, alineb.arouca@gmail.com
Received 13 June 2013; revised 14 July 2013; accepted 19 August 2013
Copyright © 2013 Aline Arouca, Dora Maria Grassi-Kassisse. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
ABSTRACT
Ginseng is one of the most popular herbal sup-
plements in the world. It is a plant widely used in
folk and traditional medicines for cardiovascular,
immune, nervous and endocrine systems, and
according to the researchers, it has the ability to
increase the non-specific resistance state, which
characterizes it as an adaptogenic substance.
There are different species of ginseng, such as
the American, Chinese, Korean and Japanese
ginseng; the Korean species (Panax ginseng) is
being used for thousands of years as a tonic,
prophylactic and “restorative” agent, with power-
ful antioxidant properties. For a long time, its
use was empirical, because people used to beli-
eve that it was a panacea that promoted longe-
vity, with beneficial effects for the treatment of
physical fatigues. Nowadays, the active compo-
nents of Eleutherococcus senticosus are well
described, however, there are no data on the
quantity of a certain class of these secondary
compounds produced in each species. Although
the Eleutherococcus senticosus extract may con-
tain several substances, including vitamins, mi-
nerals, cellulose, and ethanol, the substances
responsible for inducing various physiological
responses are the eleutherosides (in the root)
and ciwujianosides (in the leaf). As Eleutheroco-
ccus senticosus receives great attention by show-
ing that its active components can provide protec-
tion against oxidative stress, among other bene-
fits, contributing to health and the prevention
and treatment of diseases, such as diabetes, can-
cer, cardiovascular disease and inflammation.
The purpose of this article is to describe the main,
adverse and toxicological effects of Eleuthero-
coccus senticosus recently related in the litera-
ture.
Keywords: Eleutherococcus senticosus; Ginseng;
Eleutherosides; Ciwujianosides
1. INTRODUCTION
Eleutherococcus senticosus, world widely known as
Acanthopanax senticosus (Rupr. et Maxim), belongs to
the Araliaceae plant family, as well as other types of gin-
seng (Latin name), a generic term given to all species of
Panax [1]. It is also known as Siberian or Russian ginseng,
ciwujia, eleuthero, eleuthero ginseng, touch-me-not and
devil’s shrub [2,3].
Ginseng is one of the most popular herbal supplements
in the world [2]. It is a widely used plant in folk and tra-
ditional medicines for the cardiovascular, immune, ner-
vous, and endocrine systems, and according to the resear-
chers Brekhman & Dardymov (1969) [4], it has the ability
to increase the non-specific resistance state, which charac-
terizes it as an adaptogenic substance.
There are other species of ginseng, such as the Ame-
rican, Chinese, Korean and Japanese ginseng [5]; the Ko-
rean species (Panax ginseng) is being used for thousands
of years as a tonic, prophylactic and “restorative” agent
(3), with powerful antioxidant properties [6]. For a long
time, its use was empirical, because people used to believe
it was a panacea that promoted longevity, with beneficial
effects for the treatment of physical fatigue [7].
The use of Panax as a source of raw materials for phar-
maceuticals was very expensive for many years [2,5].
Therefore, a group of Russian researchers looked for al-
ternatives, and after the discovery, many years later, at the
end of 1950, Eleutherococcus senticosus (ES) was recog-
nized as a new medicinal plant [2,3]. Despite having been
described only in 1950, Eleutherococcus senticosus is a
plant used by the Chinese for over 2000 years. Some re-
ports describe its use as a medicinal remedy for the treat-
ment of infections, resistance to fatigue and for immuno-
logical improvement [8].
*This study was supported by CAPES.
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In 1982, Baranov [9] concluded that the chronic admi-
nistration of Eleutherococcus senticosus was more advan-
tageous when compared to Panax, because it does not
cause arousal in patients. It has a more intense protective
effect on the immune system; in addition, it does not lead
to the development of a similar stress syndrome. The
seasonality influences the effects of these two types of
ginseng, but there is not much variation in Eleutheroco-
ccus senticosus (ES) [3].
ES was recently included in the European Pharmaco-
poeia as a medicine derived from plants and it is, therefore,
suitable for use in traditional herbal medicines and asso-
ciations [10].
The 1994 DSHEA (Dietary Supplement Health and
Education Act) regulation allows a direct commercializa-
tion of ES as a supplement for consumption in the United
States without the regulation of the FDA (Food and Drug
Administration) [11].
2. ACTIVE COMPONENTS OF
ELEUTHEROCOCCUS SENTICOSUS
The active components of Eleutherococcus senticosus,
the eleutherosides, were initially coded from A to F [12],
and years later, Hikino et al. (1986) [13] studied seven
eleutherosides coded as A, B, C, D, E, F and G, and
through acid hydrolysis of these components, obtained the
formation of glycosides, such as rhamnose, arabinose, xy-
lose, mannose, galactose and glucose.
Based on several studies by Wagner et al. (1994) [14],
the ES components were rated as phenylpropanes, com-
pounds, lignans, coumarins, polysaccharides and other
compounds, such as oleanolic acid, aromatic oils and
sugar [8]. In an attempt to bring order to these chemicals
compounds, ES was divided into two classes: 1. Triterpe-
noid saponins, which are glycosides of oleanolic acid (re-
ferred to as eleutherosides I, K, L and M), and 2. Phenyl-
propane derivatives (eleutherosides B, B1, D and E), which
are mostly glycosylated [15].
The ES root extract is standardized in 0.6% to 0.8% of
eleutherosides, depending on the extraction method of so-
lids [16,17].
Unfortunately, there are no data on the quantity of a
certain class of these secondary compounds produced in
each species. These compounds include, but are not limit-
ed to, phenylpropanoids (siringina, caffeic acid, sinapyl
alcohol, and coniferyl aldehyde), lignans (sesamin, syrin-
garesinol and its glycoside), saponins (daucosterol, β-sito-
sterol, and hederasaponine-B), coumarins (isofraxidine and
its glycoside) and vitamins (vitamin E and beta-carotene)
[15].
Eleutherococcus not only synthesizes lignans, but also
siringina, syringaresinol and sesamin; it produces and ac-
cumulates precursors of lignans, such as hydroxycinna-
mic caffeic acid and other intermediate compounds, as co-
niferaldehyde. These precursors have shown a significant
antioxidant activity [15].
Although the Eleutherococcus senticosus extract may
contain several substances, including vitamins, minerals,
cellulose and ethanol [14], the substances responsible for
inducing various physiological responses are the eleuthe-
rosides (in the root) and ciwujianosides (in the leaf) [1].
3. MAIN EFFECTS OF
ELEUTHEROCOCCUS SENTICOSUS
Eleutherococcus senticosus, as well as Panax ginseng,
seems to have a stimulating effect on the metabolism of
substrates, as it significantly alters the mobilization and
utilization of carbohydrates and fatty acids. Since the
metabolism of substrates is essential, different types of
ginseng can have ergogenic effect [5]. Table 1 shows se-
veral studies performed in humans, using a supplemen-
tation made from ES, among other types of ginseng. Ac-
cording to the studies, we may observe that the acute
supplementation has no effect on physical performance,
whereas chronic supplementation can provide significant
changes in various biochemical parameters.
Some studies, using the supplementation of Eleuthero-
coccus senticosus, report an improvement in heart rate
recovery after physical exercise, improvement of the lac-
tate removal ability, greater ability to obtain energy from
aerobic metabolism (by increasing the oxygen consump-
tion and utilization of fatty acids as a source of energy)
and, therefore, an improvement of the performance [3,8,
18-20]. These authors believe that these improvements
are due to the action of eleutherosides, responsible for in-
ducing various physiological responses, which are pre-
sent in the root of Eleutherococcus senticosus [1].
The extracts from different parts of ES have been con-
sidered good for health [21]. The ES antioxidant effect is
related to improvements in the treatment of diabetes,
cancer and inflammatory state, in addition to their immu-
noregulatory and immunomodulatory property, and anti-
microbial and antiviral activity [11].
Six secondary compounds found in Eleutherococcus
senticosus have demonstrated antioxidant effects (such as
siringina, caffeic acid, ethyl aldehyde, coniferyl alde-
hyde), four had antioxidant effects in cancer (sesamin, β-
sitosterol, isofraxidine), and three had hypocholesterole-
mic activities (sesamin, β-sitosterol and β-sitosterol 3-D-
glucoside) [15].
Sesamin and siringina demonstrated immunostimula-
tory activity, while isofraxidine showed choleretic activ-
ity. Siringina demonstrated radioprotective property, and
antibacterial activity of caffeic acid [15].
The hypocholesterolemic activity of sesamin, β-sitos-
terol compounds and its glycoside β-sitosterol β-D-glu-
copyranoside can be explained by their participation in
antioxidant reactions on LDL (low density lipoprotein),
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A. Arouca, D. M. Grassi-Kassisse / Health 5 (2013) 1509-1515
Copyright © 2013 SciRes. OPEN ACCESS
1511
Table 1. Effects of some types of ginseng on physical performance in humans.
Ginseng Experimental design Results
Standardized extract of Panax ginseng 200
mg/day, during 9 weeks.
[28]
Men, n = 20, data collected-aerobic
capacity. Increased aerobic capacity, reduced
lactate production and heart rate.
Standardized extract of Panax ginseng containing
4% or 7% of ginsenosides, during 9 weeks.
[29]
Young men, n = 30, data
collected-aerobic capacity
Improved aerobic capacity, reduced lactate
production and heart rate, there was no
difference between 4% and 7% of the
content of ginsenosides.
Standardized extract of Panax ginseng 200
mg/day, during 9 weeks.
[30]
High performance athletes, n = 30,
data collected-O2 uptake.
Improved O2 uptake, maximum breathing
capacity, vital capacity and forced expiratory
volume, reduced lactate production and
heart rate; no significant changes for
serum LH, testosterone, and cortisol.
Glycosides, 2000 mg/day; 1.5%, during 4 weeks.
[31] Marathon runners, n = 12, data
collected-aerobic capacity.
No significant difference on the running time
to exhaustion, aerobic capacity, heart rate,
VE, and RPE.
Standardized extract of ARM229, 2 capsules per
30 days; 1 capsule per 30 days.
[32]
Young people (18 - 21 years), and
adults (38 - 70 years), n = 65, data
collected-performance in Cooper Test.
In the adult group, there was an improved
performance in the Cooper test (12 min race),
and in the young group there was no
significant difference.
Standardized extract of P. ginseng (G115), 200
mg/day, during 9 weeks.
[33]
High performance athletes, n = 28,
data collected-effects on the
health of athletes.
Improved O2 uptake, forced expiratory
volume, vital capacity, reaction time
and heart rate.
E. senticosus M, during 8 days.
[34] Young men, n = 6, data collected-maximal
work capacity. Significant increase in total work,
time to exhaustion
Chinese ginseng and Eleutherococcus senticosus,
during 6 weeks.
[35]
Marathon runners, n = 15 (M) and n = 15 (W),
data collected-aerobic performance,
physical strength.
Significant increase in VO2max,
physical strength.
Ginseng and fenu-greco 0.5 g twice a day, during
15 days.
[36]
Young men, n = 12, data
collected-strength and muscle fatigue.
Significant increase in the production of
work, significant differences in
the lactate level.
Ginseng and fenu-greco 0.5 g twice a day, during
30 days.
[37]
Well-trained amateur cyclists, n = 14, data
collected-training, endurance performance.
Significant increase in anaerobic threshold,
blood ferritin, work, RER, VEmax,
VO2max; blood lactate is not significant.
Standardized extract of P. ginseng, 200 mg/day,
DMAE, vitamins, minerals, during 6 weeks.
[38]
People (21 - 47 years), n = 50, data
collected-work and aerobic capacity.
Improved the total workload, time to
exhaustion, aerobic capacity, ventilation,
VO2, carbon dioxide production, lactate
production and heart rate; no significant RER.
Standardized extract of P. ginseng, 400 mg/day
during 20 weeks.
[39]
Female triathletes (24 - 36 years, n = 43),
data collected-physical performance. Prevented the decrease in the physical
performance after 10 km.
P. ginseng C.A. Meyer 200 mg/day at 4%
ginsenosides, during 8 weeks.
[40]
Healthy adult women, n = 19, data
Collected-Metabolic responses. No significant difference in the sub
maximal and maximal exercise.
E. senticosus M 3.4 mL during 8 weeks.
[41]
People trained in distance running, n = 20,
data collected-Maximal and sub
maximal aerobic exercise.
No significant difference in the heart rate,
VO2, VE, VE/VO2, RER, RPE, time to
exhaustion and lactate level.
P. ginseng C.A. Meyer 200 mg/day at 4%
ginsenosides during 8 weeks.
[42]
Healthy adult women, n = 19, data
collected-work performance and
energy metabolism.
No significant difference in the performance of
maximum work, rest, exercise, recovery of O2,
RER, VE, heart rate, blood lactate levels.
Standardized extract of P. ginseng, vitamins,
minerals, 200 mg/day during 12 weeks.
[43]
Volunteers (18 - 65 years), n = 625,
data collected-quality of life. Improved quality of life, preventing
weight gain and increased blood pressure.
P. quinquefolium 8 or 16 mg/Kg/ day during 7
days.
[44]
Well-trained amateur cyclists, n = 7 (M), n = 1
(W), data collected-exhaustion at 75% VO2 max
There was no significant difference
in time to exhaustion, lactate levels and
glucose, RPE, VE, VO2

A. Arouca, D. M. Grassi-Kassisse / Health 5 (2013) 1509-1515
1512
Continued
P. ginseng C.A. Meyer 200 ou 400 mg/day,
during 8 weeks.
[45]
Healthy adult men, n = 31, data
collected-psychological and
physiological responses.
No significant difference in maximal
and submaximal O2 uptake, RER, VE,
blood lactate, heart rate and RPE.
Ginseng not especified 3 g/day, during 13 days.
[46]
Well-trained amateur cyclists, n = 7 (M) and
n = 4 (W), data collected-aerobic
exercise maximum.
There was no significant difference in
maximal heart rate, VO2max, workload,
RER.
P. ginseng 200 mg/day, 7% ginsenosides, during
3 weeks.
[47]
Moderately trained healthy young adults,
n = 20 (M) and n = 8 (W), data
collected-maximum aerobic performance.
There was no significant difference in VO2,
workload, exercise time, lactate, levels of
hematocrit, heart rate, RPE.
E. senticosus 1200 mg/day, during 7 days before
data collection
[3]
Well-trained men, n = 10, data
collected-substrate utilization,
maintenance of performance.
No significant difference in VO2, RER, RPE,
rate, heart rate, level of lactate and glucose.
P. ginseng C.A. Meyer 400 mg/day, during 8
weeks.
[48]
Healthy adult women, n = 24, data
collected-aerobic capacity, fatigue. There was no significant difference in the
supramaximal work of short duration.
Extract fluid of Taiga Wurzel-25 drops 3 x/day (1
mL equivalent to 1 g root) during 30 days.
[8]
Healthy volunteers (n = 50, W and M),
data collected-total cholesterol, LDL
cholesterol, free fatty acids,
triacylglycerol, glucose, VO2max.
Significant reduction in total cholesterol and
LDL cholesterol levels, reduction of free
fatty acids, triacylglycerol, blood glucose,
and significant increase in peak VO2max.
Panax not ginseng
1350 mg/day, during 30 days.
[49]
Young adults, n = 29, data collected-aerobic
capacity, endurance, mean arterial
pressure and VO2.
Significant improvement in endurance,
time to exhaustion, decrease in the mean
arterial pressure and VO2.
Standardized extract of E. senticosus
800 mg/day, during 8 weeks.
[20]
Men in recreational cycling training, n = 9,
data collected-aerobic capacity, maximum
heart rate, VO2, RPE, RER, free fatty acids
and glucose in the plasma.
Significant increase in peak VO2, heart rate
and improvement in endurance time. The
production of free fatty acids in the plasma
was increased, and the glucose level
decreased significantly (P < 0.05) in 30 min
within 75% of peak VO2.
Panax ginseng
200 mg, 1 hour before running on a treadmill,
acute study.
[50]
Recreational athletes racing (n = 9, 25 - 32
years), data collected-aerobic capacity, VO2,
heart rate, body temperature, RPE, glucose,
lactate, plasma insulin, free fatty acids.
Acute supplementation did not affect any
of the parameters analyzed in the study.
Korean ginseng extract, 20 g, mixed with 200 mL
of water 3x/day, during 7 days before the test, and
four days after the test.
[51]
Male college students, n = 18, data
Collected-Exercise-induced muscle
damage, inflammatory response,
insulin sensitivity.
Significant decrease in creatine kinase and
interleukin 6 in the group supplemented
with ginseng, and a significant decrease in
plasma insulin and glucose, suggesting
reduced muscle damage and decreased
inflammatory response, resulting in
improvements in insulin sensitivity.
W = women; M = men; O2 = oxygen; RER = respiratory exchange ratio; RPE = rate of perceived exertion; VE = expiratory volume; VEmax = forced expiratory
volume; VO2 = oxygen uptake; VO2max = maximum oxygen uptake; LH = luteinizing hormone, n = number of volunteers. Reference number between [ ],
Source: Adapted and updated from Barke & Morgan [2] and Bucci [52].
and also, the sesamin has a direct effect on cholesterol
re-synthesis. β-sitosterol also has an important effect on
the cholesterol structure, reducing its absorption (as de-
monstrated in humans) and the ability to reduce insulin
concentrations, as well as and antioxidant effects regard-
ing cancer. β-sitosterol also has anti-inflammatory and
antipyretic activities [15].
The antihyperglycaemic action of β-sitosterol and its
glycoside can be explained by the competitive enzyme in-
hibition in glucose breakdown, but it does not end the
possibilities for this property [15].
The study by Rhie and Won (2004) [22] demonstrated
the potent effect on body weight gain of mice treated with
ES, which was significantly reduced, besides demon-
strating a significant reduction in the plasmatic choles-
terol concentration. One hypothesis for this important ef-
fect in reducing weight could be explained by the action of
ES on glucose and insulin metabolism [20], besides the ef-
fect of lower concentrations of corticosterone in rats [11,23].
4. ADVERSE EFFECTS OF
ELEUTHEROCOCCUS
SENTICOSUS
A case was reported on the use of Eleutherococus sen-
ticosus in a man who used digoxin and who had high
plasmatic concentration (digoxin). When the supplemen-
Copyright © 2013 SciRes. OPEN ACCESS

A. Arouca, D. M. Grassi-Kassisse / Health 5 (2013) 1509-1515 1513
tation was interrupted, the plasmatic concentration de-
creased [24]. Diabetics who use ES should monitor blood
glucose concentrations, due to the hypoglycemic effects
reported in animals [25].
5. TOXICOLOGICAL EFFECTS
The safety and efficacy of the ES supplement were
evaluated on the activities of CYP2D6 of the cytochrome
P450 and CYP3A4 [26], suggesting that the ES extract at
a dose as it is usually recommended does not affect the
metabolism of CYP2D6 and CYP3A4, and, therefore, it is
not harmful to the health of individuals [11,27].
6. CONCLUSION
ES may receive great attention by showing that its ac-
tive components can provide protection against oxidative
stress, among other benefits, contributing to health and
the prevention and treatment of diseases such as diabetes,
cancer, cardiovascular disease and inflammations. How-
ever, the researches comprise mostly in vitro tests or ani-
mals tested in vivo in the laboratory, and the studies may
not necessarily apply to humans. When they apply, there
may be no reliable results due to factors such as diet, life-
style, exercise and the administration of other drugs, and
also the actual health of the participants. Nevertheless, it
is expected that further controlled studies in humans are
performed for a better understanding of the ES effects and
its implementation, conferring it an economic importance,
since it may help in the treatment of several diseases.
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