Eleutherococcus senticosus

Common Names: Siberian Ginseng

Clinical Names: Eleutherococcus senticosus

Summary

botanical name: Eleutherococcus senticosus.

common name: Siberian Ginseng

overview of interactions:
• herb potentially affecting drug class performance and toxicity: Chemotherapy

• herb possibly affecting drug pharmacokinetics: Digoxin

• herbal synergy: Insulin

• herb possibly affecting drug performance and toxicity: Phenelzine

• herb potentially affecting drug performance: Sulfonylureas

• herb possibly affecting drug performance and toxicity: Warfarin

AHPA Botanical Safety Rating: 1

see also:
• Herb Groups: Neuroendocrine: Hypothalamic-Pituitary Agents/Adaptogens
• Herb Groups: Immunological: Immune-modifiers



Clinical

botanical name: Eleutherococcus senticosus.

common name: Siberian Ginseng, Eleuthero.

part used: Root, rhizome.

qualities: Slightly bitter, sweet, dry, neutral.

affinities: Hypothalamic-pituitary-adrenal axis, immune, endocrine and nervous systems.

actions: Adaptogen, Immunomodulator.

dosage:
• Tincture: (1:5) 3-5 ml. three times per day.
• Liquid Extract: (1:1) 1-2ml.three times daily
• Dried herb: 1.5-3g by decoction, three times daily.

therapy:
Stress, chemotherapy protection, fatigue, hypertension, ischemic heart disease, immune compromise, infertility, menopause, recuperation from disease or surgery, radiation protection. Tonic for Elders. Possibly useful in cancer, diabetes, depression, alcoholism and mental disorders.

specific indications:
Temporary fatigue, general debility, chronic inflammatory conditions, convalescence. Considered to be less stimulating than Panax ginseng.

AHPA Botanical Safety Rating: 1

toxicity:
• Negligible toxicity.
• LD50 (PO) dogs, >33ml/KG for ethanolic extract.
• Side effects are of low incidence, and reports include insomnia, irritability, anxiety, tachycardia, palpitations, and headaches.
(Newall C, et al. 1996, 143.)

contraindications:
• None Known.
• Commission E states, without explanation, that Eleutherococcus to be contraindicated in hypertension. Evidence is lacking, and Eleutherococcus is used therapeutically in herbal prescriptions to normalize elevated blood pressure. The Commission E position conflicts with, and is considered overly conservative by other authorities.
(Blumenthal M, et al 1998, 124; Bradley PR, 1992 90; McGuffin M, et al.1997, 45.)

cautions:
• As with Panax ginseng, long term use is not traditionally recommended. Bradley and Commission E endorse this view. The ginsengs are normally reserved for the weak, convalescing and elderly and traditionally are not considered appropriate for use by robust and healthy younger individuals.
(Blumenthal M, et al 1998, 124; Bradley PR, 1992 90.)

• Pregnancy and lactation: evidence of teratogenicity in animals is negative, but human data are lacking. Given its wide spectrum of activities and endocrine effects the herb is best avoided in pregnancy and lactation, despite its low toxicity.

constituents:
• Phenyl propanoids: incl. syringin (Eleutheroside B), caffeic and chlorogenic acids and esters.
• Lignans: Eleutherosides D, E, B4.
• Coumarins: Eleutheroside B1.
• Sterols: Beta-sitosterol, Eleutheroside A.
• Polysaccharides, m.wt ca 30,000 and 150,000. Heteroglycans ( eleutherans A-G), simple sugars.
(Bradley PR.1992, 89.)

pharmacology:
The eleutherosides are chemically heterogeneous and have complex multi-system effects. The original Soviet work has been reviewed by Farnsworth and by Collison, and animal and human research is summarized here according to these reviewers.
• Immune modulation activity: Eleutherococcus extracts promote interferon-gamma production by lymphocytes, increase NK, T helper and cytotoxic lymphocyte activity.
• Protection against toxic stressors: Eleutherococcus extracts reduce inflammatory responses, protect against IP introduction of various drugs, and increase resistance to infection, reduce sensitivity to bio-toxins, and bio-stressors such as hypothermia.
• Protection against radiation and chemotherapy: see clinical trials below.
• Performance enhancement: Eleutherococcus extracts increase endurance, physical motor activity, and in humans concentration and psycho-physical performance parameters.
• Cardiovascular activity: Eleutherococcus extracts are anti-aggregatory, anti-edema and anti-inflammatory in rat models of inflammation. In long-term use the extracts are hypotensive in humans, usually used in combination hypotensive prescription.
• Metabolic activity: Eleutherococcus extracts have steroidal activity in vitro binding to mineralocorticoid, glucocorticoid and estrogen receptors. They are anabolic, and have hypoglycemic activity in animals. Some evidence for "adaptogenic" effects on insulin-glucagon-epinephrine exist - the extracts are hyperglycemic in the early stages of stress and hypoglycemic in the "post adaptation" phase of the general stress response.
• Reproductive activity: Eleutherococcus extracts increase sperm counts and volume of ejaculate in bulls.
(Collison RJ, B J Phytother 1991; 2(2):61-71; Farnsworth N, et al. in Wagner H, 1985.)

clinical trials:
• oncology: several trials have supported the use of Eleutherococcus extracts as adjunctive treatment in chemotherapy and radiotherapy. Studies have shown enhancement of anti-tumor and anti-metastatic actions of anti-cancer therapies, together with accelerated recovery of hematopoetic indices such as leucocyte count.
(Williams M, B J Phytother 1993; 3(1):32-37)
• Other: clinical trials in the former USSR have claimed efficacy of Eleutherococcus extracts in a wide range of conditions, including atherosclerosis, hypertension, diabetes, pulmonary disorders including TB, as well as in increased performance in healthy individuals. (See reviews by Farnsworth and Collison)
(Collison RJ, B J Phytother 1991; 2(2):61-71; Farnsworth N, et al. in Wagner H, 1985.)



Interactions

herb potentially affecting drug class performance and toxicity: Chemotherapy

• mechanism: Many studies have been published looking at the immune-enhancing effects of Eleutherococcus, particularly in its role as an adaptogen.

• research: Most of the research and clinical trials of Eleutherococcus were conducted in The Soviet Union and, more recently, Russia. One key area of investigation has been the combination of Eleutherococcus and various forms of chemotherapy. In studies involving patients with melanoma, inoperable breast cancer and other types of cancer researchers reported diminished adverse effects from and increased tolerance of chemotherapeutic drugs. Outside Russia Hacker and Medon examined the cytotoxic effects of Eleutherococcus extracts in combination with various agents against leukemia cells. They reported that Eleutherococcus appeared to be potentially useful for reducing the concentration of conventional antimetabolites used for their antiproliferative effects on tumor cells.
(Kupin VJ, 1984; Kupin VI, et al. Sov Med 1987;(5):114-116; Monokhov BV. Vopr Onkol 1965;11(12):60-63; Hacker B, Medon PJ. J Pharm Sci 1984 Feb;73(2):270-272.)

• herbal support: Individuals undergoing chemotherapy for cancer should consult their treating physician and/or a healthcare professional trained in herbal medicine about potential value of adding Eleutherococcus to their regime before starting such supplementation.

herb possibly affecting drug pharmacokinetics: Digoxin

• report: A case of elevated serum digoxin level in a patient taking Siberian ginseng and digoxin was reported by McRae. The mechanism of interaction remains unclear and since the ECG was unchanged, it is possible that the herb interfered with the digoxin assay.
(McRae S. CMAJ 1996 Aug 1;155(3):293-295, Comment in: CMAJ 1996 Nov 1;155(9):1237.)

• herbal concern: Individuals taking digoxin should advise their prescribing physician before commencing Siberian ginseng consumption to ensure adequate monitoring of both plasma drug levels and cardiac signs.

herbal synergy: Insulin

• research: Sotaniemi et al conducted a double-blind placebo-controlled study involving 36 diabetic (NIDDM) patients. The subjects were treated for 8 weeks with ginseng (100 or 200 mg) or placebo and efficacy was evaluated through a variety of standard psychophysical tests. They found that ginseng use was associated with elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. Subjects who were given the 200 mg dose of ginseng also demonstrated improved glycated hemoglobin, serum PIIINP, and physical activity.
(Sotaniemi EA, et al. Diabetes Care. 1995 Oct;18(10):1373-1375.)

• herbal concerns: The study refers to Panax ginseng. Eleutherococcus also has pronounced hypoglycemic activity and cautions regarding Panax ginseng may be, speculatively, extended to Eleutherococcus. The hypoglycemic action of ginseng may render it a therapeutically efficacious adjunct in the treatment of diabetics. However, individuals taking insulin should not undertake the use of ginseng without first consulting their prescribing physician and coordinating care with a healthcare professional trained in herbal medicine. As noted below in the general section dealing with hypoglycemic herbs, blood glucose levels should always be monitored carefully when herbs with hypoglycemic activity are administered to individuals with blood glucose disorders.

herb possibly affecting drug performance and toxicity: Phenelzine

• reports: Anecdotal reports have suggested possible interactions between phenelzine and "ginseng," including a range of psychological symptoms such as excessive dreams. These reports cannot be taken as reliably implicating "ginseng" with MAOI interactions since no confirmation is stated that Eleutherococcus senticosus or Panax ginseng was definitely involved, nor were doses given.
(Jones BD, Runikis AM. J Clin Psychopharmacol 1987 Jun;7(3):201-202; Shader RI, Greenblatt DJ. J Clin Psychopharmacol 1988 Aug;8(4):235; Staba EJ. Lancet 1985 Dec 7;2(8467):1309-310; Barna P. Lancet 1985 Sep 7;2(8454):548; Shader RI, Greenblatt DJ. J Clin Psychopharmacol 1988 Aug;8(4):235.)

herb potentially affecting drug performance: Sulfonylureas

• mechanism: Eleutherococcus extracts have hypoglycemic activity.

• herbal concern: Hypoglycemic herbs have the potential to interact with drugs affecting blood glucose levels. Reports of interactions are absent.

herb possibly affecting drug performance and toxicity: Warfarin

• reports: Several case reports involving potential interactions between warfarin and Panax ginseng have been published. In two cases vaginal bleeding was associated with the use of substances reported to contain ginseng. Hopkins et al attributed the one instance of postmenopausal bleeding to ginseng's estrogen-like effect on genital tissues. a case report by Janetzky and Morreale described a possible interaction between warfarin and ginseng as evidenced by a reduction of the international normalized ratio (INR), indicating a decrease in warfarin activity, in a patient on warfarin.
(Hopkins MP, et al. Am J Obstet Gynecol 1988;159(5):1121-1122; Greenspan EM. JAMA 1983;249(15):2018; Janetzky K, Morreale AP. Am J Health-Syst Pharm 1997;54:692-693.)

• herbal concerns: Individuals using warfarin should consult with their prescribing physician and a healthcare professional trained in botanical prescribing before taking ginseng or introducing other medicinal herbs into their therapeutic regime. While the actual identity and dosage of the herbs involved in the cases found in the literature remains uncertain, they most likely involved the use of Panax ginseng, also known as Chinese or Korean ginseng. Even so, the cautions might be extended to also cover Siberian ginseng (Eleutherococcus senticosus) which, although it is a distinctly different plant and a member of a different genus, also has anti-aggregatory activity.

see also:
• Herb Groups: Neuroendocrine: Hypothalamic-Pituitary Agents/Adaptogens
• Herb Groups: Immunological: Immune-modifiers

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

References

Barna P. The case of ginseng. Lancet 1985 Sep 7;2(8454):548.

Blumenthal M, Busse WR, Goldberg A, et al, eds. The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, MA: Integrative Medicine Communications, 1998.

Bradley PR, ed. Eleutherococcus in British Herbal Compendium, vol 1. Bournemouth, Dorset, UK: British Herbal Medicine Association, 1992.

Collison RJ, Siberian Ginseng: (Eleutherococcus senticosus Maxim) B J Phytother 1991; 2(2):61-71.

Farnsworth NR, et al. Siberian Ginseng: (Eleutherococcus senticosus ) in Wagner H, et al. eds. Economic and medicinal Plant research, Volume 1 . London, Academic Press, 1985.

Greenspan EM. Ginseng and vaginal bleeding. JAMA 1983 Apr 15;249(15):2018. (Letter)

Hacker B, Medon PJ. Cytotoxic effects of Eleutherococcus senticosus aqueous extracts in combination with N6-(delta 2-isopentenyl)-adenosine and 1-beta-D-arabinofuranosylcytosine against L1210 leukemia cells. J Pharm Sci 1984 Feb;73(2):270-272.
Abstract: The use of the aqueous extracts of Eleutherococcus senticosus in combination with either cytarabine or N6-(delta 2-isopentenyl)-adenosine gave additive antiproliferative effects against L1210 murine leukemia. The ED50 for E. senticosus root extracts against L1210 cells was approximately 75 micrograms/mL. E. senticosus appears to be potentially useful for reducing the concentration of conventional antimetabolites used for their antiproliferative effects on tumor cells.

Hopkins MP, Androff L, Benninghoff AS. Ginseng face cream and unexplained vaginal bleeding. Am J Obstet Gynecol 1988 Nov;159(5):1121-1122.
Abstract: A case of postmenopausal bleeding attributed to the use of topical ginseng is reported. Ginseng appears to have an estrogen-like effect on genital tissues.

Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health-Syst Pharm 1997 Mar 15;54(6):692-693.

Jones BD, Runikis AM. Interaction of ginseng with phenelzine. J Clin Psychopharmacol 1987 Jun;7(3):201-202. (Letter)

Kupin VJ. Eleutherococcus and Other Biologically Active Modifiers in Oncology. Moscow: Medexport, 1984.

Kupin VI, Polevaia EB, Sorokin AM. [Immunomodulating action of an Eleuterococcus extract in oncologic patients]. Sov Med 1987;(5):114-116. [Article in Russian]

McGuffin M, et al.(eds.) AHPA Botanical Safety Handbook . CRC Press, 1997.

McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ. 1996 Aug 1;155(3):293-295.
Abstract: A 74-year-old man taking a constant dose of digoxin for many years was found to have an elevated serum digoxin level with no signs of toxic effects. Common causes of elevated serum digoxin were ruled out, and the patient's digoxin level remained high after digoxin therapy was stopped. The patient then revealed that he was taking Siberian ginseng, a popular herbal remedy. The patient stopped taking ginseng, and the serum digoxin level soon returned to an acceptable level. The digoxin therapy was resumed. The patient resumed taking ginseng several months later, and the serum digoxin level again rose. Digoxin therapy was maintained at a constant daily dose, the ginseng was stopped once more, and the serum digoxin levels again returned to within the therapeutic range. It is unclear whether some component of the ginseng was converted to digoxin in vivo, interfered with digoxin elimination or caused a false serum assay result. The author cautions physicians to be alert to the potential for herbal remedies to interact with prescribed medications and to affect biochemical analyses.

Monokhov BV. [Influence of the liquid extract from the roots of Eleutherococcus.] Vopr Onkol 1965;11(12):60-63. [Article in Russian]

Newall C, Anderson L, Phillipson JD. Herbal Medicines: A Guide for Health-care Professionals. London. The Pharmaceutical Press, 1996.

Shader RI, Greenblatt DJ. Bees, ginseng and MAOIs revisited. J Clin Psychopharmacol 1988 Aug;8(4):235. (Editorial)

Shader RI, Greenblatt DJ. Phenelzine and the dream machine-ramblings and reflections. J Clin Psychopharmacol 1985 Apr;5(2):65. (Editorial)

Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care. 1995 Oct;18(10):1373-1375.
Abstract: OBJECTIVE: To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS: In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. RESULTS: Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. CONCLUSIONS: Ginseng may be a useful therapeutic adjunct in the management of NIDDM.

Shader RI, Greenblatt DJ. Bees, ginseng and MAOIs revisited. J Clin Psychopharmacol 1988 Aug;8(4):235. (Editorial)

Shader RI, Greenblatt DJ. Phenelzine and the dream machine-ramblings and reflections. J Clin Psychopharmacol 1985 Apr;5(2):65. (Editorial)

Staba EJ. Ginseng. Lancet 1985 Dec 7;2(8467):1309-1310.

Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care. 1995 Oct;18(10):1373-1375.
Abstract: OBJECTIVE: To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS: In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. RESULTS: Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. CONCLUSIONS: Ginseng may be a useful therapeutic adjunct in the management of NIDDM.

Williams M, Eleutherococcus senticosus: the use of biological response modifiers in oncology. B J Phytother 1993; 3(1):32-37