Scientific Name(s): Eleutherococcus senticosus (Rupr. et Maxim.) Maxim
Common Name(s): Devil's shrub, Eleuthero, Eleutherococcus, Kan Jang, Shigoka, Siberian ginseng, Touch-me-not, Wild pepper
E. senticosus belongs to the same family (Araliceae) as Panax ginseng and is synonymous with Acanthopanax senticosus (Rupr. ex Maxim.) Harms. The geographical distribution of eleutherococcus coincides with that of P. ginseng in forests of broadleaf trees, including spruce and cedar. It grows at elevations of up to 800 m or more above sea level. The plant is a shrub, commonly growing to a height of 2 to 3 m or, less commonly, 5 to 7 m. It has gray or grayish-brown bark, numerous thin thorns, and long-stalked and palmate leaves. Eleutherococcus has separate male and female plants with globular umbrella-shaped flowers. Male plants produce violet flowers, while female plants have yellowish flowers; the fruit are black, oval berries. Most commonly, the root is used in herbal medicine; however, the leaves and berries also produce pharmacologically active metabolites. Because it grows abundantly in areas such as Russia and China, eleutherococcus has become a popular substitute for Chinese ginseng.1, 2
Eleutherococcus has been used and studied extensively in Russia. It is used as a health food, tonic, and sedative in China and wider Asia, as well as in traditional Korean folk medicine as a tonic, an adaptogen, and to strengthen "qi" (life force).3, 4
As with its relative Chinese ginseng, root extracts of the plant have been promoted as "adaptogens," which aid the body in responding to external (eg, environmental) and internal (eg, disease) stress. The plant extract has been traditionally used to normalize high or low blood pressure, to stimulate the immune system, and to increase work capacity. Reputed effects include increasing body energy levels, protecting from motion sickness and against toxins, controlling alloxan-induced diabetes, reducing tumors, and controlling atherosclerosis.2, 5
The chemical composition of the roots and leaves varies with season. The roots contain the maximum active ingredient in October, with the level dropping sharply in July. Methanolic extracts of eleutherococcus root contain a glycoside fraction that includes various eleutherosides (isofraxidin, sesamin, syringin) as well as glucose, sucrose, betulinic acid, vitamin E, beta-carotene, caffeic acid, and beta-sitosterol. The eleutherosides found in the roots, leaves, and berries are designated as A through M and have varied structures belonging to different groups of chemical compounds.2, 6
Several studies have differentiated between the botany, chemistry, and pharmacology of common ginseng (P. ginseng and P. quinquefolium) and Siberian ginseng (E. senticosus).7 Only eleutheroside A has a saponin structure similar to that of ginseng ginsenosides/panaxosides.8 While some eleutherosides share common properties with panaxosides, others exhibit very different effects. Seven glycans (eleutherans A, B, C, D, E, F, and G) have been isolated from aqueous extract of the crude drug shigoka (Siberian ginseng) root.9 The following new lignans have been isolated from the root of eleutherococcus: 7SR,8RS-dihydrodrodiconiferyl alcohol, dehydrodiconiferyl alcohol, 7,8-trans-dihydrodehydrodiconiferyl alcohol-4-O-beta-D- glucopyranoside, meso-secoisolariciresinol, and (-)-syringoresinol-4-O-beta-D-glucopyranoside.10 The antiplatelet compound 3,4-dihydroxybenzoic acid has also been isolated from this species.11 Eleutherosides have been isolated, identified, and measured in the rhizomes, roots, and liquid extracts of eleutherococcus.12 Other relatively new compounds that have been isolated include phenylpropanes and polysaccharides, ciwujianosides C1 and D113 and at least 10 phenolic compounds such as isofraxidin.14 Chemical analysis methods for eleutherococcus, such as reversed phase high-performance liquid chromatography, have been published.15, 16, 17
Uses and Pharmacology
Many clinical studies in the literature use combinations of several natural products, including eleutherococcus, making it difficult to attribute outcomes to any single plant or extract.
Although not clearly established, eleutherococcus appears to exert an endothelium dependent, nitric oxide-mediated vascular relaxation.18
At high dosages, Siberian ginseng led to abrupt cessation of myocardial contractions in rats with increased levels of intracellular calcium. At low doses, the extract induced cells to beat with a regular and strong rhythm and had no effect on calcium levels, suggesting a negative effect on developing fetal myocytes.19
In a study that examined the effects of eleutherococcus in hypotensive children between 7 and 10 years of age, an eleutherococcus extract improved subjective signs, raised systolic and diastolic blood pressures, and increased total peripheral resistance.20 In another study in 20 hypertensive elderly patients, no effect on blood pressure was found at 300 mg/day of dry extract. Higher dosages were not studied.21
Chronic fatigue/mental stress
In a review of older studies, a trend toward improved performance in mental tasks was observed.25
A study investigating the effect of eleutherococcus 2 g/day in adults with chronic idiopathic fatigue showed an improvement after 1 month, but this effect was not sustained at 2 months.26 In a study in elderly patients, self-reported mental health and social functioning was enhanced by administration of dry eleutherococcus extract 300 mg for 4 weeks. With continued use of the extract, these differences were attenuated21 possibly consistent with the concept that adaptogens should only be used in a "pulsed" manner.
Eleutherococcus has been dubbed the "herb of Russian athletes,"30 but both supporting evidence and negative trials exist regarding outcome variables, such as oxygen consumption, respiratory exchange, heart rate, and plasma glucose.30 Dosing in these trials has been up to 4 g/day.
Measurements of testosterone and cortisol have shown a detrimental effect on the recovery process similar to that of overtraining.30
In an animal study of endurance, oral administration of eleutherococcus extract did not affect plasma lactic acid, glucagon, insulin, or liver glycogen. Decreased plasma glucose levels were found in resting rats.28 In a small trial in healthy, nondiabetic adults, postprandial glucose levels were raised following eleutherococcus administration31 suggesting that caution should be used when administering the product to diabetic patients.
Aqueous extracts of the stem of the eleutherococcus plant reduced serum tumor necrosis factor and aspartate and alanine transaminases, improved histology, and inhibited hepatocyte apoptosis in mice with induced hepatic failure.4
Aqueous extracts of Siberian ginseng showed a protective effect, possibly due to cyclo-oxygenase-2 inhibition, in transient focal cerebral ischemia induced by artery occlusion in rats.3
A protective effect is suggested based on experiments in induced osteoporotic mice. Decreased urinary excretion of calcium and increased plasma levels of calcium and phosphorous were observed.34
Eleutherococcus extract binds to progesterone, mineralocorticoid, and glucocorticoid receptors.35 Siberian ginseng extracts exerted no effect on prolactin in rats despite the high concentrations and long periods of exposure used in experimentation.36 Additionally, eleutherococcus compounds bind to estrogen receptors, with no apparent effect in cell cultures.37
Eleutherococcus extract appears to protect cell cultures from the effects of gamma radiation but to a lesser degree than common ginseng. The mechanism seems to involve alteration of cellular metabolism rather than DNA repair.38, 39
As an adaptogen, eleutherococcus has been given as powdered root in doses of 1 to 4 g/day.30
Eleutheroside compounds have 36 to 143 times the physiologic activity of the roots from which they are extracted. Extracts of E. senticosus are recommended at less than 1 g/day.5
Pregnancy / Lactation
Information regarding safety and efficacy during pregnancy and lactation is lacking.
Because of a potential effect on developing fetal myocytes, use of Siberian (and other) ginseng is contraindicated during pregnancy.19
Based on experiments with standard comparators (dextromethorphan for CYP2D6 and alprazolam for CYP3A4), it is unlikely that eleutherococcus compounds rely on the CYP-450 pathways for elimination.40
The interaction of Siberian ginseng with digoxin has been the subject of many papers and case reports. Interference with the digoxin assay, impaired elimination of digoxin, and possible confounding with compounds other than eleutherococcus have all been suggested as reasons for this apparent effect.20, 40, 41, 42, 43
Mice exhibited increased sleep latency and duration when exposed to eleutherococcus extract and hexobarbital, which may be due to inhibition of hexobarbital metabolism.44
In rats, no significant effect on the kinetics of warfarin was observed with concomitant "Kan Jang" (mixed eleutherococcus extract preparation) administration.45
Adverse reactions, toxicity, contraindications, and warnings similar to those for Panax species (see Ginseng, Panax) apply.
High doses of eleutherococcus are associated with irritability, insomnia, and anxiety. In human trials, few adverse reactions are reported.21, 32 Adverse reactions have included skin eruptions, headache, diarrhea, hypertension, and pericardial pain in rheumatic heart patients; however the contraindication of aterial hypertension reported for eleutherococcus has been disputed as not being evidence-based.46
Eleutherococcus was associated with increased aggressive behavior in mice.29
In a small study, Siberian ginseng demonstrated a hyperglycemic effect in healthy adults so caution should be used when administering to diabetic patients.31 In other reports, adverse reactions have included slight languor or drowsiness immediately after administration, possibly due to a hypoglycemic effect.
Use of eleutherococcus extract has been associated with little or no toxicity.2, 7, 8 No pathologic, cytotoxic, or histologic changes were noted in mice that ingested infusions of the plant for up to 96 days.29
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