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.

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.

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.

• 1.Brekhman II, Maianskii GM. Eleutherococcus—a means of increasing the nonspecific resistance of the organism. Izv Akad Nauk SSSR Biol (Russian) 1965;5:762-765.View Abstract
• 2.Brekhman II, Dardymov IV. New substances of plant origin which increase nonspecific resistance. Annu Rev Pharmacol 1969;9:419-430.View Abstract
• 3.Panossian A, Wikman G, Wagner H. Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode of action. Phytomedicine 1999;6:287-300.View Abstract
• 4.Wagner H, Norr H. Plant adaptogens. Phytomedicine 1994;1:63-76.
• 5.Panossian A, Wagner H. Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother Res 2005;19:819-838.View Abstract
• 6.Farnsworth NR, Kinghorn AD, Soejarto DD, Waller DP. Siberian ginseng (Eleutherococcus senticosus): current status as an adaptogen. In: Wagner H, Hikino HZ, Farnsworth NR, eds. Economic and Medicinal Plant Research. 1 vol. London: Academic Press; 1985:155-215.
• 7.McKenna D, Jones K, Hughes K, Humphrey S. Eleuthero. Botanical Medicines. 2nd ed. Binghamton, NY: Haworth Press; 2002:255-270.
• 8.Davydov M, Krikorian AD. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look. J Ethnopharmacol 2000;72:345-393.View Abstract
• 9.Baranov AI. Medicinal uses of ginseng and related plants in the Soviet Union: recent trends in the Soviet literature. J Ethnopharmacol 1982;6:339-353.View Abstract
• 10.ESCOP. Eleutherococci Radix. ESCOP Monographs: The Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003:142-149.
• 11.WHO. Radix Eleutherococci. WHO Monographs on Selected Medicinal Plants. 2 vol. Geneva: World Health Organization; 2002:97-105.
• 12.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs^. Austin, TX: American Botanical Council: Integrative Medicine Communications; 1998.
• 13.BHMA. Eleutherococcus. In: Bradley P, ed. British Herbal Compendium. Bournemouth, UK: British Herbal Medical Association; 1992:89-91.
• 14.Bensky D, Clavey S, Stogër E, Gamble A. Ci Wu Jia. Chinese Herbal Medicine: Materia Medica. 3rd ed. Seattle: Eastland Press; 2004:735-736.
• 15.Vereshchagin IA, Geskina OD, Bukhteeva ER. [Increased effectiveness of antibiotic therapy with adaptogens in dysentery and Proteus infection in children]. Antibiotiki 1982;27:65-69.View Abstract
• 16.Henderson GL, Harkey MR, Gershwin ME et al. Effects of ginseng components on c-DNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 1999;65:PL209-PL214.View Abstract
• 17.Donovan JL, DeVane CL, Chavin KD et al. Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers. Drug Metab Dispos 2003;31:519-522.
• 18.Stukov AN. Eleutherococcus senticosus and spontaneous leukosis in mice. Vopr Onkol (Russian) 1965;11:64-65.View Abstract
• 19.Shen ML, Zhai SK, Chen HL et al. Immunomopharmacological effects of polysaccharides from Acanthopanax senticosus on experimental animals. Int J Immunopharmacol 1991;13:549-554.View Abstract
• 20.Schmolz MW, Sacher F, Aicher B. The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L. roots. Phytother Res 2001;15:268-270.View Abstract
• 21.Bohn B, Nebe CT, Birr C. Flow-cytometric studies with Eleutherococcus senticosus extract as an immunomodulatory agent. Arzneimittelforschung 1987;37:1193-1196.View Abstract
• 22.Wang JZ, Mao XJ, Ito H, Shimura K. Immunomodulatory activity of polysaccharide from Acanthopanax obovatus roots. Planta Med 1991;57:335-336.View Abstract
• 23.Wang JZ, Tsumura H, Ma N et al. Biochemical and morphological alterations of macrophages and spleen cells produced by antitumor polysaccharide from Acanthopanax obovatus roots. Planta Med 1993;59:54-58.View Abstract
• 24.Wagner H, Proksch A, Riess-Maurer I et al. [Immunostimulating action of polysaccharides (heteroglycans) from higher plants]. Arzneimittelforschung 1985;35:1069-1075.View Abstract
• 25.Xie SS. [Immunoregulatory effect of polysaccharide of Acanthopanax senticosus (PAS). I. Immunological mechanism of PAS against cancer]. Zhonghua Zhong Liu Za Zhi 1989;11:338-340.View Abstract
• 26.Rogala E, Skopinska-Rozewska E, Sawicka T et al. The influence of Eleuterococcus senticosus on cellular and humoral immunological response of mice. Pol J Vet Sci 2003;6:37-39.View Abstract
• 27.Glatthaar-Saalmuller B, Sacher F, Esperester A. Antiviral activity of an extract derived from roots of Eleutherococcus senticosus. Antiviral Res 2001;50:223-228.View Abstract
• 28.Jeong HJ, Koo HN, Myung NI et al. Inhibitory effects of mast cell-mediated allergic reactions by cell cultured Siberian ginseng. Immunopharmacol Immunotoxicol 2001;23:107-117.View Abstract
• 29.Kupin V, Polevaya E, Sorokin A. Increased immunologic reactivity of lymphocytes in oncologic patients treated with Eleutherococcus extract. In: Brekhman I, ed. New Data on Eleutherococcus: Proceedings of the Second International Symposium of Eleutherococcus. Moscow: Vladivostok: DVNTS AN SSSR, 1986; 1984.
• 30.Kupin VI, Polevaia EB. Stimulation of the immunological reactivity of cancer patients by Eleutherococcus extract. Vopr Onkol (Russian) 1986;32:21-26.View Abstract
• 31.Monakhov BV. Eleutherococcus senticoccus extract and therapeutic activity of cyclophosphamide, ethymidine or benzo-tepa. Vopr Onkol (Russian) 1967;13:94-97.
• 32.Monakhov BV. Reduction of toxicity of some antiblastoma drugs by Eleutherococcus extract. Vopr Onkol (Russian) 1967;13:71-76.
• 33.Hacker B, Medon PJ. Cytotoxic effects of Eleutherococcus senticosus aqueous extracts in combination with N6-(δ-2-isopentenyl)-adenosine and 1-β-d-arabinofuranosylcytosine against L1210 leukemia cells. J Pharm Sci 1984;73:270-272.
• 34.Brekhman II. Report on the use of Eleutherococcus with breast cancer patients. Eleutherococcus: Clinical Data. Institute of Oncology, Georgia: USSR Foreign Trade Publication, Medexport, USSR; 1970.
• 35.Yonezawa M, Katoh N, Takeda A. Radiation protection by Shigoka extract on split-dose irradiation in mice. J Radiat Res (Tokyo) 1989;30:247-254.View Abstract
• 36.Miyanomae T, Frindel E. Radioprotection of hemopoiesis conferred by Acanthopanax senticosus Harms (Shigoka) administered before or after irradiation. Exp Hematol 1988;16:801-806.
• 37.Minkova M, Pantev T. Effect of Eleutherococcus extract on the radioprotective action of adeturone. Acta Physiol Pharmacol Bulg 1987;13:66-70.View Abstract
• 38.Medon PJ, Ferguson PW, Watson CF. Effects of Eleutherococcus senticosus extracts on hexobarbital metabolism in vivo and in vitro. J Ethnopharmacol 1984;10:235-241.View Abstract
• 39.Medon PJ, Thompson EB, Farnsworth NR. Hypoglycemic effect and toxicity of Eleutherococcus senticosus following acute and chronic administration in mice. Zhongguo Yao Li Xue Bao 1981;2:281-285.View Abstract
• 40.Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh: Churchill Livingstone; 2000.
• 41.McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. C MAJ 1996;155:293-295.View Abstract
• 42.Harkey MR, Henderson GL, Gershwin ME et al. Variability in commercial ginseng products: an analysis of 25 preparations. Am J Clin Nutr 2001;73:1101-1106.View Abstract
• 43.Chen J, Chen T. Chinese Medical Herbology and Pharmacology. City of Industry, CA: Art of Medicine Press Inc; 2004.
• 44.Awang DV. Siberian ginseng toxicity may be case of mistaken identity. CMAJ 1996;155:1237.View Abstract
• 45.Dasgupta A, Wu S, Actor J et al. Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays: significant variation in digoxin-like immunoreactivity among commercial ginsengs. Am J Clin Pathol 2003;119:298-303.
• 46.Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy, OR: Eclectic Medical Publications; 2001.
• 47.Treasure JE. MEDLINE and the mainstream manufacture of misinformation. J Am Herbalists Guild 2006;6:50-56.