Eleutherococcus

Generic name: Eleutherococcus Senticosus (Rupr. Et Maxim.) Maxim
Brand names: Ciwujia, Devil's Shrub, Eleuthero, Eleutherococcus, Ezoukogi, Kan Jang, Shigoka, Siberian Ginseng, Touch-me-not, Wild Pepper, Wujiasheng, Wushaseng

Usage of Eleutherococcus

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.

Anti-inflammatory effects

Experimental data

Results from in silico studies predict eleutheroside B to have anti-inflammatory activity that may be similar to meclofenamic acid based on molecular docking to the cyclo-oxygenase-2 (COX-2) enzyme.(Ahmed 2021) Strong inhibition of eicosanoid signaling was exhibited by E. senticosus root extract in neuroglial cells, which decreased gene expression of ALOX12 by 7.4-fold, the arachidonic acid enzyme associated with neurotoxicity. Additionally, a 3.7-fold decrease was seen with ALOX5AP that is associated with inflammation, chemotaxis, allergic asthma, Alzheimer disease, tau phosphorylation, and vascular permeability. In contrast, the extract increased gene expression of PTGER3 related to bicarbonate secretion that reduces damage to the duodenum and is also associated with reducing allergic reactivity, fever, and pain.(Panossian 2019)

Aqueous extracts of Siberian Ginseng showed a protective effect in transient focal cerebral ischemia induced by artery occlusion in rats, possibly due to COX-2 inhibition.(Bu 2005)

Antiviral

Clinical data

A 2020 systematic review summarized 6 clinical studies published between 1977 and 1986 that documented reduced complications (ie, pneumonia, bronchitis, genyantritis, otitis), morbidity, and mortality rates related to influenza infections in adults and children with administration of E. senticosus. Preclinical studies demonstrated efficacy of eleutherodises against human rhinovirus, RSV, and H1N1.(Panossian 2020)

Cardiac effects

Although not clearly established, eleutherococcus appears to exert an endothelium Dependent, nitric oxide-mediated vascular relaxation.(Kwan 2004)

Animal data

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.(Poindexter 2006) In mice with pressure overload-induced cardiac hypertrophy, the eleutherococcus extract syringin decreased the expression of hypertrophic markers attenuating hypertrophy by mechanisms that appeared to be most closely related to autophagy.(Li 2017)

Clinical data

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.(Kaloeva 1986) 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.(Cicero 2004)

Other reported cardiovascular actions include effects in myocardial infarction(Afanaseva 1987) malignant arrhythmias(Tian 1989) and myocarditis.(Shang 1991)

Chronic fatigue/mental stress

In a review of older studies, a trend toward improved performance in mental tasks was observed.(Panossian 2005)

Clinical data

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.(Hartz 2004) 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 atTenuated(Cicero 2004) possibly consistent with the concept that adaptogens should only be used in a "pulsed" manner. Similarly, supplementation with E. senticosus for 8 weeks alone or in combination with stress management techniques did not produce any difference in salivary cortisol concentrations compared to stress management alone in adults with asthenia and chronic stress. The trial was an unblinded, randomized controlled study conducted in 144 adults with reduced work capacity.(Lopresti 2021)

CNS

Animal and experimenta data

In vitro studies support anti-inflammatory and a neuroprotective effects of Siberian ginseng that include downregulation of arachidonic acid signaling pathwatys involved in neurotoxicity, Alzheimer disease, neuronal survival, neurogenesis, neuroinflammation, blood-brain barrier integrity, plaque load, and Tau physophorylation.(Panossian 2019)

Aqueous extracts of Siberian ginseng showed a protective effect, possibly due to COX-2 inhibition, in transient focal cerebral ischemia induced by artery occlusion in rats.(Bu 2005) Oral administration of E. senticosus leaf aqueous extract in mice for 17 days significantly improved object recognition memory but did not affect memory retention or locomotion. Leaf extract compounds were identified in the cerebral cortex within 3 hours of administration indicating that cognitive effects were associated with penetration of Siberian ginseng across the blood-brain barrier.(Yamauchi 2019)

Diabetes

Animal data

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.(Martinez 1984)

Clinical data

In a small trial in healthy, nondiabetic adults, postprandial glucose levels were raised following eleutherococcus administration,(Sievenpiper 2004) suggesting that caution should be used when administering the product to diabetic patients.

Hepatoprotective

Animal data

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.(Park 2004)

Immunomodulation

Clinical data

Some studies indicated a modulatory effect on the immune system with enhanced T cell and lymphocyte activity(Bohn 1987, Borchers 1998) while others have shown no effect.(Gaffney 2001)

Insecticidal

The essential oil of E. senticoccus leaves showed moderate activity as a biting deterrent against the dengue mosquito vector, Aedes aegypti, with the alpha-bisabolol moiety exhibiting equivalent activity to DEET in in vitro assays. However, less significant effects were observed in cage-based repellency studies.(Zhai 2017)

Osteoporosis

Animal and in vitro data

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.(Kropotov 2002)

Eleutherococcus extract binds to progesterone, mineralocorticoid, and glucocorticoid receptors.(Pearce 1982) Siberian ginseng extracts exerted no effect on prolactin in rats despite the high concentrations and long periods of exposure used in experimentation.(Di Carlo 2005) Additionally, eleutherococcus compounds bind to estrogen receptors, with no apparent effect in cell cultures.(Bennetau-Pelissero 2004)

Physical stress/endurance

Animal data

In animal experiments, various eleutherosides have been evaluated for endurance effect, with certain compounds more effective than others.(Kimura 2004, Lewis 1983, Martinez 1984)

Clinical data

Eleutherococcus has been dubbed the "herb of Russian athletes,"(Gaffney 2001) but both supporting evidence and negative trials exist regarding outcome variables, such as oxygen consumption, respiratory exchange, heart rate, and plasma glucose.(Gaffney 2001) 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.(Gaffney 2001)

Radioprotective effects

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.(Ben-Hur 1981, Minkova 1987)

Eleutherococcus side effects

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.Bohn 1987, Cicero 2004 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.Schmidt 2014

Eleutherococcus was associated with increased aggressive behavior in mice.Lewis 1983

In a small study, Siberian ginseng demonstrated a hyperglycemic effect in healthy adults so caution should be used when administering to diabetic patients.Sievenpiper 2004 In other reports, adverse reactions have included slight languor or drowsiness immediately after administration, possibly due to a hypoglycemic effect.

Before taking Eleutherococcus

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.Poindexter 2006

How to use Eleutherococcus

As an adaptogen, eleutherococcus has been given as powdered root in doses of 1 to 4 g/day.Gaffney 2001

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.Brekhman 1991

Use in elderly patients and children has been studied to a limited extent.Cicero 2004, Hartz 2004, Kaloeva 1986

Warnings

Use of eleutherococcus extract has been associated with little or no toxicity.Brekhman 1980, Wagner 1977, Wagner 1994 No pathologic, cytotoxic, or histologic changes were noted in mice that ingested infusions of the plant for up to 96 days.Lewis 1983

What other drugs will affect Eleutherococcus

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.(Donovan 2003)

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.(Dasgupta 2003, Dasgupta 2005, Donovan 2003, Kaloeva 1986, McRae 1996)

Mice exhibited increased sleep latency and duration when exposed to eleutherococcus extract and hexobarbital, which may be due to inhibition of hexobarbital metabolism.(Medon 1984)

In rats, no significant effect on the kinetics of warfarin was observed with concomitant "Kan Jang" (mixed eleutherococcus extract preparation) administration.(Hovhannisyan 2006)

Atorvastatin: Ginseng (Siberian) may enhance the hepatotoxic effect of atorvastatin. Monitor therapy.(Laube 2019)

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