Siberian Ginseng

Health Care Professional Information

Scientific Name
Eleutherococcus senticosus, Acanthopanax senticosus
Common Name

Eleuthero, Russian ginseng, devil’s shrub, touch-me-not, wild pepper, shigoka, ci wu ja

Brand Name

Eleu-Kokk®

Clinical Summary

Siberian ginseng is derived from a perennial plant primarily found in Northern Asia. Although it is not a species of ginseng, it is thought to have comparable activities (1). Siberian ginseng, or eleuthero, has been used traditionally as an adaptogen, performance enhancer, and immunostimulant (2). Active components are thought to include several eleutherosides and polysaccharides (28).

In vitro and in vivo studies suggest that Siberian ginseng extracts have neuroprotective effects (8) and may reduce glucose levels in insulin-deficient animals (9). Eleuthero extract has also been shown to bind to estrogen, progestin, and mineralocorticoid receptors (10), and stimulate T-lymphocyte and natural killer cell production (11).

A small study in patients with knee osteoarthritis found that an herbal mixture containing Siberian ginseng relieved pain and improved physical function (5).
Siberian ginseng may also improve endurance (27); and have beneficial effects on bone remodeling (6) and in managing cholesterol levels in postmenopausal women (7).

Purported Uses
  • Chemotherapy side effects
  • Health maintenance
  • Immunostimulation
  • Strength and stamina
Constituents
  • Terpenoids: Oleanolic acid
  • Glycosides: Eleutheroside A (daucosterin), B1, C - G
  • Phytosterols: Beta-sitosterol
  • Coumarins: Eleutheroside B1 and B3, isofraxidine
  • Polysaccharides: Eleutherans
  • Others: Volatile oils, caffeic acid, coniferyl aldehyde, glucose, maltose, sucrose
    (14) (28)
Mechanism of Action

In vitro studies indicate that eleuthero contains chemicals that bind to estrogen, progestin, mineralocorticoid, and glucocorticoid receptors (10). In macrophages, a Siberian ginseng extract suppressed LPS-induced iNOS expression and thus nitric oxide production by possibly inhibiting nuclear factor-kappa B activity (15) (16) or Akt and JNK signaling (16), and inhibited reactive oxygen species production (17). Siberian ginseng extract also moderately inhibited breast cancer resistance protein (BCRP)-mediated methotrexate transport in BCRP-expressing membrane vesicles (21). Eleutheroside B, eleutheroside E, and isofraxidin — active constituents of Siberian ginseng — showed protective effects against Aβ(25-35)-induced atrophies of axons and dendrites in rat cultured cortical neurons (22). Isofraxidin also inhibited cell invasion and the expression of matrix metalloproteinase-7 by human hepatoma cell lines HuH-7 and Hep G-2, possibly through the inhibition of ERK1/2 phosphorylation (18). In animal studies, eleuthero root bark was shown to exhibit neuroprotective effects against global cerebral ischemia with recovery of spatial memory in rats, possibly through anti-inflammatory mechanisms of inhibition of COX-2 expression, microglia and astrocyte expression (23). Eleutherosides restored behavioral and biochemical alterations in mice with sleep deprivation (24), and alleviated both physical and mental fatigue in mice possibly due to increased fat utilization, delayed accumulation of blood urea nitrogen, and increased lactate dehydrogenase (25). Siberian ginseng extract also decreased cadmium concentration in the blood and liver of mice as well as cadmium-induced mitotic and apoptotic activity of liver cells (26). Siberian ginseng supplementation reduced LDL cholesterol levels and improved LDL/HDL ratios in postmenopausal women (7). Stimulation of helper/inductor T lymphocytes and natural killer cells also occurs by an unknown mechanism (1).

Adverse Reactions
  • Case report: Subarachnoid hemorrhage was reported in a 53-year-old woman following use of a herbal supplement containing red clover, dong quai, and Siberian ginseng for hot flashes associated with perimenopause. Her symptoms resolved after discontinuing use of the supplement (19).
Herb-Drug Interactions
  • Digoxin: Elevates serum digoxin levels (12).
  • Cytochrome P450 substrates: Eleutherosides B and E may inhibit CYP2C9 and CYP2E1, and can affect the intracellular concentration of drugs metabolized by these enzymes (29).
Herb Lab Interactions

Siberian ginseng may cause falsely elevated digoxin serum assays (12).

Literature Summary and Critique

Hwang YC, et al. The effects of Acanthopanax senticosus extract on bone turnover and bone mineral density in Korean postmenopausal women. J Bone Miner Metab. 2009;27(5):584-90.
This randomized, open-label, controlled study enrolled 81 post-menopausal Korean women (age<65 years) with ostopenia or osteoporosis. Subjects were randomly assigned to a control (n=40) or treatment group (n=41). Both groups received 500 mg/day calcium and the treatment group also received Siberian ginseng extract. After 6 months the treatment group exhibited a significant change in plasma levels of the bone turnover markers, serium osteocalcin (p=0.041) and CTx, (C terminal telopeptide of type 1 collagen, [p<0.0001]), compared with the control group. However, no significant changes in bone density were observed, possibly due to the short treatment duration.. Siberian ginseng extract was well-tolerated and demonstrated a safety profile comparable to the control group. The authors concluded that Siberian ginseng extract is safe and may beneficially affect bone remodeling in Korean post-menopausal women.

Lee YJ, Chung HY, Kwak HK, Yoon S. The effects of A. senticosus supplementation on serum lipid profiles, biomarkers of oxidative stress, and lymphocyte DNA damage in postmenopausal women. Biochem Biophys Res Commun. Oct 10 2008;375(1):44-8.
To determine the effects of Siberian ginseng supplementation on blood lipid levels and oxidative stress, 40 postmenopausal women were randomly divided into either a control group receiving calcium (500 mg/day) or an experimental group receiving both calcium and A. senticosus capsules (500 mg tid). After 6 months, blood lipid profiles, oxidative stress, and lymphocytic DNA damage was assessed along with hepatoxicity. Serum LDL cholesterol, LDL/HDL ratio, lymphocytic DNA damage, and oxidative stress was significantly reduced in the treatment group while the control group did not experience any changes. Furthermore, no side effects were noted during this study. Future studies are required to determine if A. senticosus supplementation produces long term benefits in other study populations.

Dosage (Inside MSKCC Only)
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References
  1. Schulz V, et al. Rational Phytotherapy: A Physician's Guide to Herbal Medicine, 4th ed. New York: Springer; 2001.
  2. Harkey MR, Henderson GL, Gershwin ME, et al. Variability in commercial ginseng products: an analysis of 25 preparations. Am J Clin Nutr 2001;73:1101-6.
  3. Huang KC. The Pharmacology of Chinese Herbs, 2nd ed. New York: CRC Press; 1999.
  4. Newall C, et al. Herbal Medicines: A Guide for Health-Care Professionals, 1st ed. London: Pharmaceutical Press; 1996.
  5. Park SH, Kim SK, Shin IH. Effects of AIF on Knee Osteoarthritis Patients: Double-blind, Randomized Placebo-controlled Study. Korean J Physiol Pharmacol. 2009 Feb;13(1):33-7.
  6. Hwang YC, Jeong IK, Ahn KJ, et al. The effects of Acanthopanax senticosus extract on bone turnover and bone mineral density in Korean postmenopausal women. J Bone Miner Metab. 2009;27(5):584-90.
  7. Lee YJ, Chung HY, Kwak HK, et al. The effects of A. senticosus supplementation on serum lipid profiles, biomarkers of oxidative stress, and lymphocyte DNA damage in postmenopausal women. Biochem Biophys Res Commun. Oct 10 2008;375(1):44-48.
  8. Tohda C, Ichimura M, Bai Y, et al. Inhibitory effects of Eleutherococcus senticosus extracts on amyloid beta(25-35)-induced neuritic atrophy and synaptic loss. J Pharmacol Sci. Jul 2008;107(3):329-339.
  9. Niu HS, Liu IM, Cheng JT, et al. Hypoglycemic effect of syringin from Eleutherococcus senticosus in streptozotocin-induced diabetic rats. Planta Med. Feb 2008;74(2):109-113.
  10. Pearce PT, Zois I, Wynne KN, et al. Panax ginseng and Eleuthrococcus senticosus extracts—in vitro studies on binding to steroid receptors. Endocrinol Jpn. 1982 Oct;29(5):567-73.
  11. Szolomicki J, Samochowiec L, Wojcicki J, et al. The influence of active components of Eleutherococcus senticosus on cellular defence and physical fitness in man. Phytother Res. 2000 Feb;14(1):30-5. Erratum in: Phytother Res 2000 May;14(3):225.
  12. McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ 1996;155:293-5.
  13. Brinker F. Herb Contraindications and Drug Interactions, 3rd ed. Sandy (OR): Eclectic Medical Publications; 2001.
  14. Baranov AI. Medicinal uses of ginseng and related plants in the Soviet Union: recent trends in the Soviet literature. J Ethnopharmacol 1982;6:339-53.
  15. Lin QY, Jin LJ, Cao ZH, et al. Inhibition of inducible nitric oxide synthase by Acanthopanax senticosus extract in RAW264.7 macrophages. J Ethnopharmacol. Jul 23 2008;118(2):231-236.
  16. Jung CH, Jung H, Shin YC, et al. Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophage. J Ethnopharmacol. Aug 15 2007;113(1):183-187.
  17. Lin QY, Jin LJ, Cao ZH, et al. Acanthopanax senticosus suppresses reactive oxygen species production by mouse peritoneal macrophages in vitro and in vivo. Phytother Res. Jun 2008;22(6):740-745.
  18. Yamazaki T, Tokiwa T. Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits matrix metalloproteinase-7 expression and cell invasion of human hepatoma cells. Biol Pharm Bull 2010;33(10) 1716-1722.
  19. Friedman JA, Taylor SA, McDermott W, et al. Multifocal and recurrent subarachnoid hemorrhage due to an herbal supplement containing natural coumarins. Neurocrit Care. 2007;7(1):76-80.
  20. Dowling EA, Redondo DR, Branch JD, et al. Effect of Eleutherococcus senticosus on submaximal and maximal exercise performance. Med Sci Sports Exerc. 1996;28:482-9.
  21. Tamaki H, Satoh H, Hori S, et al. Inhibitory effects of herbal extracts on breast cancer resistance protein (BCRP) and structure-inhibitory potency relationship of isoflavonoids. Drug Metab Pharmacokinet. 2010;25(2):170-9.
  22. Bai Y, Tohda C, Zhu S, et al. Active components from Siberian ginseng (Eleutherococcus senticosus) for protection of amyloid β(25-35)-induced neuritic atrophy in cultured rat cortical neurons. J Nat Med. 2011;65(3-4):417-23.
  23. Lee D, Park J, Yoon J, et al. Neuroprotective effects of Eleutherococcus senticosus bark on transient global cerebral ischemia in rats. J Ethnopharmacol. 2011 May 27. [Epub ahead of print]
  24. Huang LZ, Wei L, Zhao HF, et al. The effect of Eleutheroside E on behavioral alterations in murine sleep deprivation stress model. Eur J Pharmacol. 2011;658(2-3):150-5.
  25. Huang LZ, Huang BK, Ye Q, et al. Bioactivity-guided fractionation for anti-fatigue property of Acanthopanax senticosus. J Ethnopharmacol. 2011;133(1):213-9.
  26. Smalinskiene A, Lesauskaite V, Zitkevicius V, et al. Estimation of the combined effect of Eleutherococcus senticosus extract and cadmium on liver cells. Ann N Y Acad Sci. 2009;1171:314-20.
  27. Kuo J, Chen KW, Cheng IS, et al. The effect of eight weeks of supplementation with Eleutherococcus senticosus on endurance capacity and metabolism in human. Chin J Physiol.2010 Apr 30;53(2):105-11.
  28. Huang L, Zhao H, Huang B, et al. Acanthopanax senticosus: review of botany, chemistry and pharmacology. Pharmazie. 2011 Feb;66(2):83-97.
  29. Ahn J, Um MY, Lee H, et al. Eleutheroside E, An Active Component of Eleutherococcus senticosus, Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice. Evid Based Complement Alternat Med. 2013;2013:934183.

Consumer Information

How It Works

Bottom Line: Siberian ginseng does not enhance athletic performance nor treat or prevent cancer.

Scientists are unsure how Siberian ginseng works. Compounds from the plant have been shown to stimulate cells of immune system and protect the nervous system but no large scale clinical trials have been conducted. Other studies have shown that Siberian ginseng supplements brought down LDL cholesterol (bad cholesterol) levels and improved the HDL (good cholesterol) levels in postmenopausal women. Small studies have shown that Siberian ginseng may reduce knee osteoarthritis pain and symptoms and benefit bone metabolism in post-menopausal women. More research is needed.

Purported Uses
  • To reduce the side effects from chemotherapy
    No scientific evidence supports this use.
  • To stimulate the immune system
    Laboratory studies show that Siberian ginseng can stimulate certain aspects of the immune system, but clinical trials have not been conducted.
  • To increase strength and stamina
    Clinical trials do not support this use.
  • To reduce the pain and symptoms of knee osteoarthritis
    One small study showed that Siberian ginseng may reduce the pain and symptoms of knee osteoarthritis. More research is needed.
  • To improve bone metabolism in post-menopausal women
    One small study showed that Siberian ginseng had a beneficial effect on bone metabolism in post-menopausal women. However, further study is needed to confirm this effect.
Research Evidence

Bone density
Eight-one post-menopausal Korean women over 65 years of age with osteopenia or osteoporosis were randomly assigned to receive 500 mg/day calcium with or without Siberian ginseng extract. After 6 months the treatment group showed a significant change in levels of the bone markers compared with the control group. However, no significant changes in bone density were observed, possibly due to the short treatment time. Siberian ginseng extract was well-tolerated. The authors concluded that Siberian ginseng extract is safe and may benefit bone health.

 

Do Not Take If
  • You are taking digoxin (Eleuthero can elevate the levels of this medication in the blood, which may increase its side effects).
Side Effects
  • Case report: Intracranial hemorrhage was reported in a 53-year-old woman following use of a herbal supplement containing red clover, dong quai, and Siberian ginseng for hot flashes associated with perimenopause. Her symptoms resolved after discontinuing use of the supplement.
Special Point
E-mail your questions and comments to aboutherbs@mskcc.org.