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PLANTS-ELEUTHEROCOCCUS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Eleutherococcus species belong to the same family as the Panax (ginseng) family, and are used in herbal medicine in the place of Panax species because it is less expensive and is reputed to have fewer side effects (Anon, 1996).

Specific Substances

    1) Acanthopanax senticosus (Rupr. et Maxim. ex. Maxim.)
    2) Devil's Shrub
    3) EL
    4) Eleuthera
    5) Eleutherococ
    6) Eleutherococcus senticosus (Maxim)
    7) Hedera senticosa
    8) Shigoka
    9) Siberian Ginseng
    10) Touch-Me-Not
    11) Wild Pepper

Available Forms Sources

    A) SOURCES
    1) SIBERIAN GINSENG is derived from Acanthopanax senticosus, also called Eleutherococcus senticosus. This plant is native to Asia, especially eastern Russia. It is encountered elsewhere as an herbal in health food stores or herbal medication shops.
    2) VARIABILITY IN PLANT CONTENT: The leaves and stems contain different chemicals and in different amounts depending on the season. The roots have the maximum active ingredient in October and the least amount of activity in July (Anon, 1996).
    3) INGREDIENTS: When the roots are extracted with methanol, a fraction is isolated that contains seven eleutherosides (glycosides), glucose, sucrose, and a number of dyes (Anon, 1996).
    4) Although eleutherococcus shares many of the same chemical constituents of Panax ginseng, the exact composition differs (Anon, 1996). The eleutherococcus leaves contain saponins which are normally found in the ginseng root. The eleutherococcus plant also contains several types of lignans and phenylpropan derivatives.
    5) There are also a number of phenylpropane derivatives and lignans that have been isolated (Wagner, 1982).
    6) The eleutherosides have physiologic activity many times (36 to 143) that of the crude root from which they are extracted (Anon, 1996).
    7) ADULTERANTS - Periploca sepium, which contains cardiac glycosides and pregnane glycosides, has frequently been found to be an adulterant or substitute in products labeled as Eleutherococcus species (Awang, 1991) (Waller et al, 1992).
    B) USES
    1) This plant is used extensively in the Soviet Union where it grows, and has also been used as an herbal in China. It is promoted as an "adaptogen" which reputedly aids the body in coping with various environmental stresses (Anon, 1996).
    2) Some other reputed uses include: increasing body energy levels, control of alloxane-induced diabetes, protection from toxins, protection from or reduction of tumors, and control of atherosclerosis (Anon, 1996).
    a) The following properties have been cited: adaptogenic, hemodynamic, immuno-boosting and protective, cardioprotective, useful in the treatment of heart disease, inhibit platelet aggregation, possible hypoglycemic properties, and a potential role in the prevention of congenital defects.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) There have been no human cases of poisoning reported after exposure to this plant in its natural form or when used as an herbal. Animal data have shown the plant to be of low toxicity when administered therapeutically.
    B) Rare reports of lethargy and drowsiness have occurred shortly after administration, and may be a result of the hypoglycemic effect of the extract.
    0.2.7) NEUROLOGIC
    A) Due to its similarity to Panax, irritability, nervousness, and restlessness might be expected in overdose. This has not been reported in the few human studies done.
    0.2.17) METABOLISM
    A) The active ingredients are known to inhibit mixed function oxidases of the liver. This may interfere with the metabolism of drugs given therapeutically or in overdose.
    1) Some animal studies suggest that Eleutherococcus may lower blood sugar. Overdose may cause hypoglycemia, but this has not been reported.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

    A) Patients should be monitored for possible hypoglycemia.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Because of the limited toxicity of this plant, GI decontamination is generally not necessary.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.

Range Of Toxicity

    A) Minimum lethal human exposure is unknown.

Clinical Effects

Summary Of Exposure

    A) There have been no human cases of poisoning reported after exposure to this plant in its natural form or when used as an herbal. Animal data have shown the plant to be of low toxicity when administered therapeutically.
    B) Rare reports of lethargy and drowsiness have occurred shortly after administration, and may be a result of the hypoglycemic effect of the extract.

Neurologic

    3.7.1) SUMMARY
    A) Due to its similarity to Panax, irritability, nervousness, and restlessness might be expected in overdose. This has not been reported in the few human studies done.
    3.7.2) CLINICAL EFFECTS
    A) DROWSY
    1) Lethargy and drowsiness have been reported as rare side effects after administration. This may be due to a lowering of blood sugar, but the cause has not been established (Anon, 1996).
    B) FEELING NERVOUS
    1) Nervousness and restlessness have occurred in some individuals following a one gram dose of P. ginseng root (Anon, 1996). Due to the chemical similarity between Panax ginseng and Eleutherosides, similar reactions might be observed following overdose with Eleutherococcus.

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) DISORDER OF IMMUNE FUNCTION
    1) Bohn et al (1987) treated a group of 36 healthy volunteers with injections of Eleutherococcus alcoholic extracts three times a day for 4 weeks. Large increases in the number of immunocompetent T cells were seen. The largest increase was in the helper/inducer cells.

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Patients should be monitored for possible hypoglycemia.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) No specific tests are indicated. Some animal studies indicate that tests for hypoglycemia may be indicated in significant overdoses.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Patients should be monitored for possible hypoglycemia.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Because of the limited toxicity of this plant, GI decontamination is generally not necessary.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific management. Treatment is symptomatic and supportive.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Minimum lethal human exposure is unknown.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) No true "therapeutic dose" has been established, but in human studies 2 milliliters of an alcohol extract was given to test subjects twice a day for eight days. Each milliliter contained 75 milligrams of soluble material from Eleutherococcus (this contained 0.53 milligram of eleutheroside B and 0.12 milligram of eleutheroside D).
    a) This dose was shown to have some pharmacologic effect (Asano et al, 1986).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Following a 1 gram dose of P. ginseng root irritability and nervousness were reported (Anon, 1996). Based on there similar chemical composition, individuals taking eleutherococcus may have the same response as that of P. ginseng ingestion.

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Siberian ginseng contains a number of eleutherosides. These all contain a methoxy group and are similar in chemical structure to the ginseng panaxosides. The eleutherosides and the panaxosides share some chemical properties, but not all of them are structurally related.
    1) Eleutherosides are relatively chemically unstable. They are usually designated with the letters A to M (Anon, 1988).
    2) Eleutheroside B appears to be syringin, and eleutheroside D is syringaresinol diglucoside (Asano et al, 1986).
    B) SLEEP - Pharmacologic studies done on mice that were given hexobarbital to induce sleep found that eleutherococcus extract increased sleep latency and sleep duration when given either 4 to 320 mg/kg acutely, or 80 to 320 mg/kg/day for 4 to 5 days.
    1) Sleep time was increased 228%. In vitro testing showed that the plant extract decreased metabolism by 66%.
    2) These experiments would seem to indicate that Eleutherococcus acts more by enzyme inhibition rather than by enzyme induction (Medon et al, 1984).
    C) SUGAR - Plasma sugar levels were reduced in mice who were given eleutherococcus root extract intraperitoneally. The hypoglycemic effect was noticed both in normal mice and in alloxane-induced diabetic mice (Hikino et al, 1986).
    1) Another study did find decreased plasma glucose levels in resting rats (Martinez & Staba, 1984). Plasma lactic acid, glucagon, insulin, or liver glycogen were not affected in another study done on rats (Anon, 1988).
    D) IMMUNOSTIMULANT - Some initial work done with animals and test models have shown immunostimulant properties (Wagner et al, 1985).
    E) ENDURANCE - Several tests in animals have failed to show increased endurance (Lewis et al, 1983) Wagner, 1985).
    1) A 1986, single-blind, crossover study on 6 males volunteers showed a 23.3% increase in total work due to the extract as compared to a 7.5% increase seen in the placebo. The test was done on a Monark bicycle ergometer (Asano et al, 1986).
    F) ANTI-LEUKEMIC - Eleutherococcus extract has shown some effect as an antileukemic agent, especially when mixed with conventional antimetabolite drugs (Hacker & Midon, 1984; (Ben-Hur & Fulder, 1981).
    G) HORMONE/STEROID EFFECT - The active ingredients from eleutherococcus extracts binds to progestin, estrogen, mineralcorticoid, and glucocorticoid receptors (Pearce et al, 1982).
    H) ENERGY METABOLISM - Another study done in rats showed an increase in the number of mitochondria in heart muscle and enhancement of energy metabolism due to eleutherococcus extract administration (Afanasjaya et al, 1985).

References

General Bibliography

    1) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    2) Anon: Eleutherococcus. The Lawrence Review of Natural Products (May), 1988.
    3) Anon: Eleutherococcus. The Lawrence Review of Natural Products (May), 1996.
    4) Anon: Siberian ginseng and the liver. The Lawrence Review of Natural Products 1984; 5:24.
    5) Asano K, Takahashi T, & Miyashita M: Eleutheroccocus senticosus extract on human physical working capacity. Planta Medica 1986; 175-176.
    6) Awang DVC: Maternal use of ginseng and neonatal androgenization. JAMA 1991; 296:363.
    7) Ben-Hur E & Fulder S: Effect of panax ginseng saponins and eleutherococcus senticosus on survival of cultured mammalian cells after ionizing radiation. Am J Chin Med 1981; 9:48-56.
    8) Bohn B, Nebe CT, & Birr C: Flow-cytometric studies with Eleutherococcus senticosus extract an an immunomodulatory agent. Arzneimittelforschung 1987; 37:1193-1196.
    9) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    10) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    11) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    12) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    13) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    14) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    15) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    16) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    17) Hikino H, Takahashi M, & Otake K: Isolation and hypoglycemic activity of eleutherans A, B, C, D, E, F, and G: glycans of Eleutherococcus senticosus roots. J Nat Prod 1986; 49:293.
    18) Lewis WH, Zenger VE, & Lynch RG: No adaptogen response of mice to ginseng and Eleutherococcus infusions. J Ethnopharmacol 1983; 8:209-214.
    19) Martinez B & Staba EJ: The physiological effects of aralia, panax and eleutherococcus on exercised rats. Jpn J Pharmacol 1984; 35:79-85.
    20) 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.
    21) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    22) Pearce PT, Zois I, & Wynne KN: Panax ginseng and Eleutherococcus senticosus extracts - in vitro studies on binding to steroid receptors. Endocrinol Jpn 1982; 29:567-573.
    23) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    24) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    25) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    26) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    27) Wagner H, Proksch A, & Riess-Maurer I: Immunostimulating action of polysaccharides (heteroglycans) from higher plants. Arzneimittelforschung 1985; 35:1069-1075.
    28) Wagner H: Planta Medica 1982; 44:193.