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Eleuthero

Botanical Name: Eleutherococcus senticosus (Rupr. and Maxim.) Maxim.
Pharmacopoeial Name: Radix Eleutherococci.
Synonym: Acanthopanax senticosus (Rupr. and Maxim.) Maxim.
Common Names: Eleuthero, Siberian ginseng.

Summary Table
herb description

Family

Araliaceae.

Habitat and Cultivation

Native to northern and eastern Russia, northern China, Korea, and Japan; commercially grown in Siberia, as well as parts of China.

Parts Used

Root; the leaf is also used in Russia.

Common Forms

  • Dried:   Powdered root.

  • Tincture:   1:5.

  • Fluid Extract:   1:1, 33% to 40% ethanol.

  • Standardized Preparations:   Usually based on eleutheroside E >1.0% and/or eleutheroside B.

herb in clinical practice

Overview

Eleuthero is considered one of the defining adaptogen medicinal plants. Adaptogens have no equivalent among conventional pharmaceutical agents. The term was coined by Soviet researcher Lazarev in 1947 and subsequently defined by Brekhman in terms of three salient qualities: nonspecific (in relation to a wide range of stressor stimuli), nontoxic (cause minimal disturbance to normal physiological function), and normalizing (direction of action varies depending on the prior state of response to stressor and always normalizes). 1,2The properties of adaptogens have been reviewed recently by Panossian 3 and Wagner. 4 Panossian and Wagner 5 also recently published an important paper distinguishing between the adaptogenic effects of the herb resulting from chronic dosing protocols compared with the stimulating effect of single acute doses.

With more than 1000 studies, eleuthero was initially the most widely studied adaptogenic herb, although Panax ginseng has a more voluminous literature. Eleuthero has established immunomodulating, anabolic, radioprotective, chemoprotective, antiviral, gonadotrophic, antiviral, and insulinotropic/antidiabetic effects; enhances learning, memory, visual and auditory acuity, and exercise endurance and recovery; and has antitoxic and antialcohol effects, as well as a range of antineoplastic actions.

Western reviews of some of the literature are available by Wagner and Norr, 4 Farnsworth et al., 6 McKenna et al., 7 Davidov and Krikorian, 8 and Baranov. 9 Therapeutic monographs are available from the European Scientific Cooperative on Phytotherapy, 10 World Health Organization (WHO), 11 German Commission E, 12 and British Herbal Medical Association. 13

Confusion over nomenclature for the herb exists both with the binomial name (it is known as Acanthopanax senticosus in Chinese medicine) and the common name; the previous name “Siberian ginseng” implies similarity with “true” Panax ginseng . The current common name “eleuthero” was recently adopted in commerce to emphasize that although both plants are adaptogenic, eleuthero is pharmacologically distinct from Panax ginseng in terms of both constituents and activity profile. Medical reports often fail to use the correct binomial designation to identify herbal ingredients, and eleuthero has notoriously been confused with the entirely different species Panax ginseng (see Ginseng monograph).

Historical/Ethnomedicine Precedent

Eleuthero root (Ci Wu Jia) has been used in traditional Chinese medicine as a spleen (Pi) and kidney (Shen) qi tonic and is claimed to calm the Spirit/Mind (Shen) . The root bark is considered a separate remedy. Eleuthero was incorporated into Western medicine in Russia in the early 1960s after two decades of Soviet research to locate more economic adaptogenic species than the slow-growing Panax ginseng , and it was introduced to the U.S. market in the 1970s. 9 As with many herbs used in Chinese medicine, Ci Wu Jia is used in complex formulae corresponding to specific classical diagnostic patterns and is prescribed in higher typical dose levels than in Western usage. 14

Known or Potential Therapeutic Uses

Stress reduction and neuroendocrine balancing (e.g., dysglycemia, adrenal deficiency); fatigue, convalescence; enhancement of stamina, exercise, athletic, and work capacity and performance; increasing mental alertness and cognitive performance (e.g., memory, visual acuity); adjunctive to radiation and chemotherapy treatment; various psychological complaints (e.g., insomnia, depression); immunoprotection and immunomodulation; prophylaxis of infection, especially viral infection; antineoplastic.

Key Constituents

Lignans and other phenylpropanoids.

A series of “eleutheroside” compounds have been identified (eleutherosides A-M), but none of these is unique to eleuthero, and not all are the eleutheroside homologous compounds.

Oleanic acid derivatives (eleutherosides I-M), senticosides A-F, and polysaccharides, including glycans (eleutherans A-G); miscellaneous sterols, saponins, vitamins, and carbohydrates.

Therapeutic Dosing Range

  • Dried Root:   2 to 3 g daily (Western); 9 to 30 g daily (Chinese).

  • Tincture:   3.0 to 12.0 mL daily (equivalent 1:1).

  • Standardized Dry Extract:   150 to 300 mg three times daily; 10:1 extracts standardized to eleutherosides B and E.

interactions review

Strategic Considerations

Authoritative monographs on eleuthero do not list any known interactions between eleuthero and pharmaceuticals. 10-13The WHO monograph does refer to a case report that suggested eleuthero extracts interacted with digoxin. This case is considered likely an issue of adulteration or of interference between certain constituents of the herb and the digoxin assay and is discussed later (see Theoretical, Speculative, and Preliminary Interactions Research).

The general adaptogenic properties of eleuthero (according to the criteria of Lazarev and Breckhman) have been substantiated by a number of indexed Western studies, particularly regarding performance enhancement, although the bulk of the supporting literature, both experimental and clinical, is in Russian-language journals, much of it dating from the 1950s through the 1970s. Authoritative evaluations of the original literature in terms of study design, statistics, methods, and materials are not generally available. In the 1980s, Farnsworth et al. 6 and Baranov 9 attempted to summarize a number of eleuthero studies from the earlier Russian literature.

From an integrative perspective, the use of eleuthero in oncological settings is of particular interest because of the putative protective effects against chemotherapy- and radiation-induced toxicity suggested by the Russian research. Unfortunately, little corroborative work has been undertaken in the West to support the Soviet-era data. This is discussed later as a generic interaction.

As with other adaptogenic herbs, the nonspecific immunomodulating properties may bring about beneficial interactions with antimicrobial agents, although for eleuthero there are minimal data on this application. 15 (See also Ginseng [Panax ginseng] monograph.)

Effects on Drug Metabolism and Bioavailability

An in vitro fluorometric probe study failed to detect any effect of eleutherosides E and B on a battery of recombinant human cytochrome P450 (CYP450) isoforms (1A2, 2C9, 2C19, 2D6, and 3A4). 16 A “before and after” study on 12 healthy human volunteers failed to establish any effect of standardized Eleutherococcus extract (485 mg twice daily) with dextromethorphan and alprazolam probes. The authors concluded that the extract is likely to alter disposition of drugs metabolized by 3A4 and 2D6. 17 From the limited data currently available, pharmacokinetic interactions caused by eleuthero effects on phase-one drug-metabolizing enzymes seems unlikely, and clinical reports of such interactions have not to date been made.

herb-drug interactions
Antineoplastic Chemotherapy, Including 6-Mercaptopurine, Cyclophosphamide
Cyclophosphamide (Cytoxan, Endoxana, Neosar, Procytox), mercaptopurine (6-mercaptopurine, 6-MP, NSC 755; Purinethol).
Potential or Theoretical Beneficial or Supportive Interaction, with Professional Management
Prevention or Reduction of Drug Adverse Effect

Probability: 2. Probable
Evidence Base: Preliminary

Effect and Mechanism of Action

Eleuthero extracts are used to reduce adverse effects of antineoplastic therapies through a variety of mechanisms, including protection against and reversal of leukopenia, reduction of chemical toxicities, and enhancement of general stress resistance.

Research

In vitro and animal studies confirm that eleuthero extracts can modulate the immune system through a variety of mechanisms. These include increases in phagocytosis, natural killer (NK), and cytotoxic T-cell activity; modulation of T helper cell types 1 and 2 (Th1 and Th2) cytokines; and increased endogenous granulocyte colony-stimulating factor (G-CSF) production. 18-28 Two human studies are available. A flow-cytometry study was performed by Bohn et al. 21 on healthy human volunteers, who consumed 10 mL of eleuthero extract three times daily for 4 weeks. Significant increases in Th1 and NK cell numbers were observed, with increased activity of T cells. Russian researchers Kupin et al. 29,30 reported stimulation of immunological reactivity in breast cancer patients treated with eleuthero extracts. Although limited, these studies suggest that eleuthero has immunostimulating and immunomodulating activities in humans.

Coadministration of eleuthero with various antineoplastic agents (as well as radiation) has been reported in a number of Russian studies. Farnsworth et al. 6 report several animal studies in the Russian literature by Monakhov 31,32 and other researchers that involved a variety of antitumor agents, including 6-mercaptopurine, cyclophosphamide, and ethydimine. An in vitro study by Hacker and Mendon 33 found that eleuthero extracts at 75 µg/mL potentiated the effects of antileukemic agents cytarabine and N6-adenosine against murine L1210 leukemia cells. In a controlled study, Brekhman 34 reported a reduction of adverse effects in a controlled study of 80 breast cancer patients undergoing chemotherapy and/or radiation treatment when treated concurrently with eleuthero extracts, compared with controls not treated with eleuthero. Radioprotective effects of the herb have also been documented. 35,36 A rodent study by Minkova and Pantev 37 found that a radioprotective drug known as “adenturone” was potentiated by prophylactic pretreatment with eleuthero, although the dose of herb used was very high (5 g/kg orally).

Integrative Therapeutics, Clinical Concerns, and Adaptations

The documented evidence supporting benefits of coadministration of eleuthero with chemotherapy and/or radiation in oncology patients is limited, but sufficient data exist to justify the inclusion of eleuthero with other adaptogenic herbs in protective protocols designed to minimize myelosuppressive side effects of cancer treatment. (See also Ginseng monograph.)

theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Digoxin and Related Cardiac Glycosides
Antimicrobial Agents, Including Aminoglycoside Antibiotics
Monoamine Oxidase-B (MAO-B) Inhibitors
Citations
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