Ginseng is one of the most popular herbal supplements 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 powerful antioxidant properties. For a long time, its use was empirical, because people used to believe that it was a panacea that promoted longevity, with beneficial effects for the treatment of physical fatigues. Nowadays, the active components 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 contain several substances, including vitamins, minerals, cellulose, and ethanol, the substances responsible for inducing various physiological responses are the eleutherosides (in the root) and ciwujianosides (in the leaf). As Eleutherococcus senticosus receives great attention by showing that its active 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 inflammation. The purpose of this article is to describe the main, adverse and toxicological effects of Eleutherococcus senticosus recently related in the literature.
Eleutherococcus senticosus, world widely known as Acanthopanax senticosus (Rupr. et Maxim), belongs to the Araliaceae plant family, as well as other types of ginseng (Latin name), a generic term given to all species of Panax [
Ginseng is one of the most popular herbal supplements in the world [
There are other species of ginseng, such as the American, Chinese, Korean and Japanese ginseng [
The use of Panax as a source of raw materials for pharmaceuticals was very expensive for many years [2,5]. Therefore, a group of Russian researchers looked for alternatives, and after the discovery, many years later, at the end of 1950, Eleutherococcus senticosus (ES) was recognized 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 reports describe its use as a medicinal remedy for the treatment of infections, resistance to fatigue and for immunological improvement [
In 1982, Baranov [
ES was recently included in the European Pharmacopoeia as a medicine derived from plants and it is, therefore, suitable for use in traditional herbal medicines and associations [
The 1994 DSHEA (Dietary Supplement Health and Education Act) regulation allows a direct commercialization of ES as a supplement for consumption in the United States without the regulation of the FDA (Food and Drug Administration) [
The active components of Eleutherococcus senticosus, the eleutherosides, were initially coded from A to F [
Based on several studies by Wagner et al. (1994) [
The ES root extract is standardized in 0.6% to 0.8% of eleutherosides, depending on the extraction method of solids [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 limited to, phenylpropanoids (siringina, caffeic acid, sinapyl alcohol, and coniferyl aldehyde), lignans (sesamin, syringaresinol and its glycoside), saponins (daucosterol, β-sitosterol, and hederasaponine-B), coumarins (isofraxidine and its glycoside) and vitamins (vitamin E and beta-carotene) [
Eleutherococcus not only synthesizes lignans, but also siringina, syringaresinol and sesamin; it produces and accumulates precursors of lignans, such as hydroxycinnamic caffeic acid and other intermediate compounds, as coniferaldehyde. These precursors have shown a significant antioxidant activity [
Although the Eleutherococcus senticosus extract may contain several substances, including vitamins, minerals, cellulose and ethanol [
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 [
Some studies, using the supplementation of Eleutherococcus senticosus, report an improvement in heart rate recovery after physical exercise, improvement of the lactate removal ability, greater ability to obtain energy from aerobic metabolism (by increasing the oxygen consumption 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 inducing various physiological responses, which are present in the root of Eleutherococcus senticosus [
The extracts from different parts of ES have been considered good for health [
Six secondary compounds found in Eleutherococcus senticosus have demonstrated antioxidant effects (such as siringina, caffeic acid, ethyl aldehyde, coniferyl aldehyde), four had antioxidant effects in cancer (sesamin, β- sitosterol, isofraxidine), and three had hypocholesterolemic activities (sesamin, β-sitosterol and β-sitosterol 3-Dglucoside) [
Sesamin and siringina demonstrated immunostimulatory activity, while isofraxidine showed choleretic activity. Siringina demonstrated radioprotective property, and antibacterial activity of caffeic acid [
The hypocholesterolemic activity of sesamin, β-sitosterol compounds and its glycoside β-sitosterol β-D-glucopyranoside can be explained by their participation in antioxidant reactions on LDL (low density lipoprotein),
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P. ginseng C.A. Meyer 200 ou 400 mg/day, during 8 weeks.
[
Healthy adult men, n = 31, data collected-psychological and physiological responses.
No significant difference in maximal and submaximal O2 uptake, RER, VEblood lactate, heart rate and RPE.
Ginseng not especified 3 g/day, during 13 days.
[
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, workloadRER.
P. ginseng 200 mg/day, 7% ginsenosides, during 3 weeks.
[
Moderately trained healthy young adultsn = 20 (M) and n = 8 (W), data collected-maximum aerobic performance.
There was no significant difference in VO2workload, exercise time, lactate, levels of hematocrit, heart rate, RPE.
E. senticosus 1200 mg/day, during 7 days before data collection
[
Well-trained men, n = 10, data collected-substrate utilizationmaintenance of performance.
No significant difference in VO2, RER, RPErate, heart rate, level of lactate and glucose.
P. ginseng C.A. Meyer 400 mg/day, during 8 weeks.
[
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.
[
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 glucoseand significant increase in peak VO2max.
Panax not ginseng 1350 mg/day, during 30 days.
[
Young adults, n = 29, data collected-aerobic capacity, endurance, mean arterial pressure and VO2.
Significant improvement in endurancetime to exhaustion, decrease in the mean arterial pressure and VO2.
Standardized extract of E. senticosus 800 mg/day, during 8 weeks.
[
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.
[
Recreational athletes racing (n = 9, 25 - 32 years), data collected-aerobic capacity, VO2heart 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.
[
Male college students, n = 18, data Collected-Exercise-induced muscle damage, inflammatory responseinsulin 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 [
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 demonstrated in humans) and the ability to reduce insulin concentrations, as well as and antioxidant effects regarding cancer. β-sitosterol also has anti-inflammatory and antipyretic activities [
The antihyperglycaemic action of β-sitosterol and its glycoside can be explained by the competitive enzyme inhibition in glucose breakdown, but it does not end the possibilities for this property [
The study by Rhie and Won (2004) [
A case was reported on the use of Eleutherococus senticosus in a man who used digoxin and who had high plasmatic concentration (digoxin). When the supplementation was interrupted, the plasmatic concentration decreased [
The safety and efficacy of the ES supplement were evaluated on the activities of CYP2D6 of the cytochrome P450 and CYP3A4 [
ES may receive great attention by showing that its active 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. However, the researches comprise mostly in vitro tests or animals 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, lifestyle, 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.