Eleuthero (Eleutherococcus senticosus): a review of its effects and mechanisms of action
3 Top benefits of Eleuthero: 1- Adaptogenic it promotes adaptation to stress and fatigue. 2- Ergogenic it enhances physical performance. 3- Antioxidant it protects tissues and organs from oxidative damage.
Sara Adaes

Sara Adaes

Ph.D Neuroscience, Neuropharmacology.
Eleutherococcus senticosus (Eleuthero, Siberian Ginseng)

Summary

Eleutherococcus senticosus (Eleuthero, Siberian Ginseng) is an adaptogenic, immunostimulant, and antioxidant herb whose effects are recognized in several European Pharmacopoeias. Eleuthero has been shown to have stimulating and tonic actions and beneficial adaptive effects on the stress response, mental and physical fatigue, and mental and physical performance.

3 Top benefits of Eleuthero

  1. Adaptogenic: promotes adaptation to stress and fatigue
  2. Ergogenic: enhances physical performance
  3. Antioxidant: protects tissues and organs from oxidative damage

Eleutherococcus senticosus (or Acanthopanax senticosus), also commonly referred to as Eleuthero, Siberian Ginseng or Russian Ginseng Root, is a herb that has been used in traditional folk medicine to manage stress, mental and physical fatigue, energy depletion, depression, anxiety, and insomnia (1).

Eleuthero is regarded as an adaptogenic herb (2) — it increases non-specific resistance to different kinds of stressors, promotes well-being, and enhances physical endurance. It has stimulating and tonic effects, meaning that it can increase work capacity (stimulating effect) after a single dose and that its stimulating effects can be maintained for a sustained period of time after a period of continued intake (tonic effect).

The efficacy of Eleuthero was extensively studied in the former USSR, where scientific research assessing its effects dated back to the 1950s. Eleutherococcus root extract was approved by the Soviet Union Pharmacological Committee for clinical use as a stimulant in the early 1960s and was recommended for use in the Soviet space program to improve adaptability to the harsh and stressful conditions of space (1). Soviet findings were later replicated by other researches and Eleuthero root extract has been adopted for medicinal use in several countries besides Russia. Eleutherococcus senticosus is included in the European Pharmacopoeia (3).

Eleutherococcus senticosus contains several compounds that have shown pharmacological effects in medically and scientifically validated tests and assays. The main bioactive ingredients of Eleuthero are called eleutherosides and are found in highest concentrations in the root of the plant. Other bioactive compounds found in Eleuthero include phenylpropanoids, lignans, triterpenoid saponins, coumarins, flavones, vitamins, and provitamins (47).

[Note: The vast majority of the early studies on Eleutherococcus senticosus were published in Russian with no available English translations. However, they have been summarized in several review articles or books published in English. Data on the results of older Russian studies mentioned in this article were obtained from those books and articles or from monographs published by governmental agencies.]

Adaptogenic, anti-stress, and anti-fatigue effects

Numerous human trials on the adaptogenic effects of Eleutherococcus senticosus have been conducted, many of which between the 1960s and 1980s in the Soviet Union. Many of these studies focused on determining whether Eleuthero could increase the resistance to several different types of physical and emotional stress, and consequently, reduce mental disturbances, such as anxiety, depression, excitability, or insomnia, and improve physical and mental performance in those contexts.

However, it is important to note that many of those early studies were not conducted in accordance with the current standards of adequate scientific rigor; many lacked controls and statistical evaluation, for example. Nevertheless, given the large number of studies carried out between the 60s and the 80s, the large number of subjects included in those studies, and the contexts in which Eleuthero was recommended and used in the USSR, it seems that the evidence of adaptogenic effects was compelling.

A review of 35 Soviet clinical studies with Eleuthero root extract carried out before 1985 and involving over 2100 healthy subjects indicated that Eleuthero is effective in improving physical and mental performance under stressful conditions (1, 8). Eleuthero root extract appears to exert adaptogenic and anti-stress effects by increasing the body’s defenses against stress factors and harmful compounds in a non-specific way, by stimulating the immune system, and by promoting a general enhancement of physical and mental performance (8).

A large Russian study with 357 sailors receiving an Eleutherococcus senticosus extract demonstrated that Eleuthero had adaptogenic and other beneficial effects even after a single dose. In normal (non-stressful) conditions, it was shown that a single administration of Eleuthero improved mental performance in a correction test, increased the activity of the adrenal gland and sympathetic nervous system, improved metabolic processes, and enhanced redox processes. In stressful conditions, a single administration of Eleuthero promoted adaptation by decreasing the activity of the adrenal cortex and sympathetic nervous system, increasing the tonus of the parasympathetic nervous system, moderately increasing central nervous system excitation, and improving endurance to hypoxia (9).

Eleuthero root extract was shown to improve the psychophysical and cognitive performances of 190 pilots, co-pilots and flight engineers in the Arctic (1, 10). Eleuthero administered to patients with neurosis was also shown to improve sleep, well-being, appetite, stamina, cognitive function, and mood (11).

Although more recent randomized, double blind, placebo-controlled trials with Eleuthero are not abundant, there is evidence that supports those earlier findings. For example, it was shown that Eleuthero reduces the cardiovascular responses to stress of healthy individuals subjected to a stressful cognitive task (12). In a study with subjects with chronic, unexplained fatigue, Eleuthero root extract administered for 2 months (at a dose of 2000 mg/day standardized to provide 2.24 mg eleutherosides B and E) was effective in decreasing fatigue, but only in individuals with moderate fatigue and not in those with severe fatigue (13).

Interestingly, Eleuthero root extract was shown to improve short-term memory in healthy humans, but it was also shown that the effect depended on the time of day and on the psychophysiological characteristics of the volunteers (1, 14). In another study, Eleuthero root administered to healthy humans was shown to improve aural memory and decrease reactive anxiety, but again, these effects were shown to dependent on the time of day and the individual circadian features of each subject. Statistically significant effects were observed in evenings for morning people  and in mornings for evening people (1, 15).

The anti-stress effects of Eleutherococcus senticosus have also been extensively studied and demonstrated in animal research, where Eleuthero has shown positive effects in protecting from the effects of both acute and chronic stress (16). Eleuthero-treated animals were shown to be less prone to stress responses in behavioral tests (16). Eleuthero administered daily to stressed rats normalized the stress-induced changes in the function and in the weights of the adrenal and thyroid glands (which are usually shrunken by stress) (1), and had protective effects against stress-induced gastric ulcer (17). Animals receiving Eleuthero also showed anti-fatigue effects, both physical and mental (1821),  and improved learning and memory abilities (22).

Ergogenic effects, physical performance enhancement

The effects of Eleutherococcus senticosus extracts on sports performance were also extensively studied in the Soviet Union. In experiments carried out in male and female Olympic athletes (including sprinters, 5 and 10 kilometer runners, marathon runners, high-jumpers, and decathlon competitors), it was shown that Eleuthero root extract improved endurance performance and shortened the recovery time (1, 23). In a review of the Soviet scientific literature (8), it was reported that Eleuthero increased the resistance of skiers to low levels of oxygen in the blood and improved their adaptation to exercise demands. In another review of Soviet studies (24), it was referred that Eleuthero improved the performance of runners participating in a 10-kilometer race.

More recent studies on physical performance have also shown that Eleuthero may be able to improve endurance performance, cardiovascular function, and recovery in healthy athletes or recreationally trained individuals (25, 26). A randomized, active-controlled study on the effect of an Eleuthero extract on the physical performance of healthy volunteers showed that Eleuthero administration for 30 days improved measures of physical fitness — individuals reached a significantly higher oxygen consumption plateau during exercise, indicating an increased upper limit of physical stress (27).

However, there have also been studies in which Eleuthero failed to produce beneficial effects on physical performance. For example, in a double-blind study involving nine endurance cyclists, daily administration of Eleuthero for seven days did not significantly alter perceived exertion, oxygen consumption or other physiological responses (28).

Antioxidant and protective effects

It has been suggested that the adaptogenic and protective effects of Eleutherococcus senticosus may be largely due to the many phenolic compounds with antioxidant action it contains (4). In line with this possibility, there have been many studies that highlighted that antioxidant effects of Eleuthero. Eleuthero supplementation administered to postmenopausal women for 6 months was shown to decrease the levels of markers of oxidative stress (29).

Antioxidant effects have also been shown in animal studies. Eleuthero has been shown to be a strong antioxidant, able to reduce the nitric oxide (NO) and lipid peroxidation levels, to increase the activities of antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase, and to increase the content of reduced glutathione (3032). It was also shown to be an effective free radical scavenger (33, 34).

Since oxidative stress is a major cause of tissue and organ dysfunction, it would be expected that the antioxidant effects of Eleuthero could contribute to the protection of tissues and organs. Accordingly, Eleuthero was shown to protect cardiac muscle cells against oxidative-stress injury by enhancing antioxidant defenses (31). Eleuthero also protected against kidney dysfunction (32), liver injury and dysfunction (3437), and brain damage caused by cerebral ischemia (38).

The neuroprotective effects of Eleuthero seem to be due not only to an antioxidant effect, but also to an inti-inflammatory activity, since Eleuthero was shown to inhibiting inflammation and microglial activation in brain ischaemia (38). Furthermore, Eleuthero also protected neurons against neuritic atrophy and cell death caused by neurotoxic agents (amyloid beta) (39).

Extracts of Eleutherococcus senticosus (containing 2.1% eleutherosides B+E) significantly increased the resistance of the nematode Caenorhabditis elegans to heat stress and oxidative stress, and favored the synthesis of proteins involved in stress resistance (such as the chaperone HSP-16) and longevity. Importantly, Eleuthero increased the mean lifespan of C. elegans between 10 and 20% and delayed the moment when the first individuals in a population died, indicating an anti-aging effect. A noteworthy finding was the fact that this effect depended on the dose, with higher doses causing less beneficial effect; at highest concentration tested, a lifespan shortening effect was actually observed, indicating that, at excessive doses, Eleuthero may lose its beneficial effects (40).

Immunostimulation and immunomodulation

Many human studies have demonstrated that Eleutherococcus root extract, given prophylactically, can stimulate and modulate the immune system, reduce the overall disease incidence, and increase resistance to infections and its complications (6, 8, 24, 41, 42). Eleuthero was shown to support cellular defense mechanisms, decrease DNA damage in lymphocytes, and promote immune cell activity (27, 29).  Immunomodulatory effects were also demonstrated in experimental research: Eleuthero was shown to increase immune cell activity, to inhibit the replication of specific types of viruses (RNA viruses, such as influenza A virus), and to modulate the production of inflammatory mediators (4346).

Mechanisms

The anti-stress effects of Eleuthero may be linked to the modulation of stress-induced corticosteroid signaling. It has been shown that Eleutherococcus senticosus extract contains compounds that may bind to steroid receptors, particularly glucocorticoid receptors, which are involved in the stress response (47). Eleuthero may thereby prevent the activation of glucocorticoid receptors by cortisol, which may underlie its anti-stress effects in humans. Accordingly, Eleuthero, through the action of eleutheroside E, was shown to reduce the stress-induced increase in corticosterone levels (the main glucocorticoid in rats) (43).

Another possible mechanism of action is the modulation of the brain levels of biogenic amines. Eleuthero was shown to increase the concentration of noradrenaline and dopamine in the rat brain (16, 22). Administration for 2 weeks preferentially acted on the frontal cortex and anterior hypothalamus to enhance noradrenaline levels and its turnover, and the long-term administration stimulated dopamine and its turnover in the striatum and anterior hypothalamus (22). This indicated that Eleuthero regulates noradrenaline and dopamine levels in brain regions involved in the stress response. This is accordance with a study assessing neuronal activation in the rat brain in response to Eleuthero  administration, which showed a neuroanatomical pattern of activation of areas that regulate stress response (48).

Eleuthero was shown to increase serotonin synthesis and the expression of tryptophan hydroxylase (the rate-limiting enzyme in serotonin synthesis) in the dorsal raphe of rats, which may underlie its anti-fatigue effects (21). Furthermore, animal experiments have shown that administration of Eleuthero extracts can cause EEG alterations that indicate a stimulatory effect on the central nervous system (22).

Dosage and duration of use

There are several different preparations of Eleutherococcus senticosus extracts.
Dosage depends on the type of extract.

  • Dosage of the 33% ethanolic root extract is 10 mL three times per day;
  • Dosage of the crude extract of the root is 2-3 g/day;
  • Dosage of extracts standardized to ~2% eleutheroside B and E is 300-400 mg/day.

The daily dose can be taken in one to three doses.

Any of these dosing regimens should not to be taken for more than 2 months without a break of two weeks before continuing (5, 6).

Safety, interactions, and contraindications

Eleutherococcus senticosus is generally well tolerated. In recent clinical studies, no side effects were reported (26, 29). Within the recommended doses, there should be no major adverse effects (1, 42).

Eleutherococcus senticosus is not considered to be toxic or teratogenic (5). Given the chemical composition and pharmacological actions of Eleutherococcus senticosus and its compounds, it is possible that Eleuthero extracts may interact with drugs with anticoagulant, hypoglycaemic and/or hypo/hypertensive activity (6). Eleutherococcus senticosus may interact with the antibiotics monomycin and kanamycin, the radioprotector drug adeturone, and the cardiac drug digoxin. There is speculation that Eleuthero may interact with antipsychotic drugs, barbiturates, and sedatives. In theory, Eleuthero may lower blood glucose levels in persons with diabetes (49).

Conclusion

The medicinal use of Eleutherococcus senticosus is recognized and approved by several governmental agencies and Eleuthero is included in the European Pharmacopoeia.

Most research on the adaptogenic effects of Eleutherococcus senticosus was conducted between the 1960s and the 1980s in the USSR. Although there were some flaws in those studies, the vast amount of research and large number of subjects included in those studies, along with reported uses of Eleuthero in the USSR, indicate compelling evidence of adaptogenic, anti-fatigue, and physical and mental performance-enhancing effects. A few recent studies have confirmed those effects.

Research indicates that Eleuthero increases the body’s stress defenses, immune defenses, anti-inflammatory defenses, and, most notably, antioxidant defenses.

Eleuthero was shown to well tolerated and have protective effects in several organs and systems, thereby indicating a general beneficial effect.

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