Siberian Ginseng

Siberian Ginseng

Siberian Ginseng  (Eleutherococcus Senticosus)  

Introduction  Siberian Ginseng is a bush related with Asian Ginseng (Panax ginseng) which grows in the taigas of South-East Russia, in the North-East of China , Korea , South-East Asia, and on the Japanese island of Hokkaido .It is known in Chinese medicine since almost 2000 years but its adatpogenic properties were discovered and exhaustively studied in 1946 in the Academy of Sciences of the Soviet Union by Dr. I. Brekhman. There are more studies published about Eleutherococcus senticosus than about any other plant. These studies show that eleutherococcus senticosus is one of the principle primary adaptogenes which contributes to the organic adaptation to stress, leading to the homeostasis of organs and systems. Therefore, it has been given to the astronauts who had to stay in an isolated condition during long periods, to neutralize the stress of spatial voyages.
Siberian Ginseng

Siberian Ginseng


Synonyms  
Acanthopanax senticosus (Rupr. et Maxim) Harms., Hedera senticosa.Popular NamesBuisson du diable, chi wu cha, ciwujia, arbusto del Diablo, eleuthero, eleutherococc, eleutherococoque, eleutherokokk, koljucij, ezoukogi, gashi ohgap, hongmao-wujiapi, acanthopanax thornbush, pai wu cha pi, eleutherococco thornbush, shigoka, Siberian ginseng, Stachelkraftwurz, Stachelpanax, taiga root, taigawurzel, ginseng thornbush, Russian pepper thornbush, don’t touch me, tsu wu cha, savage pepper, wu cha sang, wu cha seng, wu jia pi.DescriptionIt is a thorny bush with a height up to 4 – 6 mts. With few ramifications. The oldest stems usually do not have any thorns, while the younger ones are densely covered with flexible thorns. The leaves have reddish stems, usually with five elliptical parts and sawed edges. The small polygamist flowers appear at the points of the stems alone or in couples with large peduncles. The floral parts appear in groups of five, including epigenous ovaries, surrounded by a disc which secrets some nectar. The fruit contains the same number of nucleuses and carpel. The fruits and flowers look like the ones of the hedera (Hedera helix). The roots are cylindrical of up to 0,5 cmts. diameter, straight or occasionally ramified with an even surface and the bark adheres to the xylem. The rhizomes have a thickness of 4 cmts., light brown, with longitudinal cracks, showing scars of roots and traces of aerial stems.Organoleptic PropertiesSmell: weak, aromatic. Taste: bitter, acre, persistent.
Active Compounds:The parts to use are the roots and the rhizomes (Eleutherococci radix). There have bee no less than 35 active substances identified in the roots of Eleutherococcus senticosus, the most important ones apparently being:1. Eleutherosids (0,6 – 0,9%):

. Eleutherosid A (daucosterol, beta-sistosterol glucosid)

. Eleutherosid B (siringine)

. Eleutherosid B1 (isofraxidine, isofraxidine glucosid)

. Eleutherosid B4 (sesamine)

. Eleutherosid D and E (siringorresinol heterosid)

. Eleutherosid I, K, L and M (saponosids, derivates of oleanolic acid)

2. Phytosterols:

. Beta-sitosterol

. Beta-stigmasterol

3. Phenylpropanoids:

. Cafe acid, free or sterificated. Conipherylic aldehyde.

4. Other active compounds include:

. Flavonoids

. Immune-stimulating heterogeneous polysaccharides (Eleutherans A – G)


Medicinal Actions:

1. Adaptogenic Actions

Increases the levels of energy and vitality, improving the physical and mental performance and quality of life. Increases the contribution of oxygen to the muscles and allows for longer exercising and faster recovery. Prevents tiredness. Reduces the glycogenolosis and the production of lacteous and pyruvic acids during exercises. Reduces the psychological tiredness and accelerates the intellectual recovery during resting. Numerous life studies show the protective effect of eleutherococo against physical and mental stress. Animals treated with ethanolic extracts of eletherococo and irradiated with gamma rays show higher levels of nucleic acids. Snail grubs (lymnaea stagnalis) pre-treated with the watery extract (with 1% eleutherosid E and 0,34% of eleutherosid B) present a higher survival rate when exposed to a thermal shock. The extracts of this plant achieved the thermal normalization of mice that received hypothermia. Numerous clinical studies with humans, designed to measure its adatpogenic effects, were realized in Russia during the decades of the 60s and 70s. In 35 clinical studies on over 2,100 healthy persons, the oral administration of eleuthero improved the physical and mental performance under stress conditions and reduced auditive alterations and the incidence of sicknesses. In some other 35 clinical studies on 2,200 patients with various diseases like: arteriosclerosis, acute pielonyphritis, diabetes, arterial hypertension, chronic bronquitis, and rheumatic carditis, there were positive results, e.g. the normalization of arterial hypertension, the levels of prothrombine and cholesterol decreased and the physical performance and the feeling of wellbeing improved. A placebo-controlled blind study with 6 athletes showed its efficiency for maximum working capacity. Three studies using ergogenic bicycles showed an improvement of oxygen utilization, partial concentration of blood oxygen and total working time.

Action Mechanism

The anti-stress or adatpogenic effects of the root of eleutherococco are produced by metabolic regulation of energy, nucleic acids, and titular proteins. Eleuthero improves the formation of glucose-6-phosphate, a substance which reduces the competition between the different ways of use. In animals with ATP deficiency, the glucose-6-phosphate oxidizes by the way of pentose, producing substrates for the biosynthesis of nucleic acids and proteins. On the other hand, it increases the activity of succhinate dehydrogenase and of muscular malato dehydrogenase, enzymes that intervene in the cycle of tricarboxylic acids, generating ATP. The eleutherosids B and E are responsible for this adaptogenic activity.

2. Endocrine Activity

Increases the sexual vigor, erection, seminal production and fertility. Has gonadothropic activity. It has been proved, in vitro, that the extract interacts competitively with the mineralocorticoid and glucocorticoid receptors. The extract induces an increase of the ACTH secretion and of the luteinizant hormone, in primitive cultivations of pituitary cells of rats. Furthermore, the siringine and the diglucosid siyngaresinol induce a strong increase of the luteinizant hormone. However, the liberation of the pholic-stimulating hormone (FSH) is inhibited. The influence of eleutherococo on the pituitary adrenal system has been verified in life studies, but there does not exist any evidence for its influence on the pituitary gonodal system. The intraperitoneal administration of the extract increases the corticosterone levels in rats; but reduces the increase of the weight of spleen and thymus produced by the administration of cortisone. In animals under stress and treated with the watery extract, the ACTH liberation is completely inhibited. The corticosterone increases in animals without any stress and treated with the extract. However, in stress situations, the liberation of corticosterone is significantly reduced. Another study with rats shows that it reduces the growth of adrenal glands induced by stress. The intragastric administration to mice (500 mg/kg) improved its sexual behavior.

3. Immune Stimulant

Increases the activation and the number of lymphocytes T supports and NK, increases the phagocytosis and the interferon production. Has been used for the prevention and the treatment of viral infections and in the long term treatment of sicknesses of the immune system, including AIDS and the syndrome of chronic tiredness. In vitro, the extract to the eleutherococo root stimulates the phagocytosis of human leucocytes (an action attributed to polysaccharides) and does not produce any effect on the lymphocytary proliferation. Furthermore, induces the production of interleukine-1 (IL-1) and IL-6. In life studies the isolated polysaccharids of the eleutherococo root, administered intraperitoneally to mice, have an immune-stimulating effect, observed in the test of carbon elimination. A double blind chance study, placebo controlled, measured the effects of eleuthero on the immune system: 36 healthy persons received 10 ml. Of the extract or placebo three time per day during 4 weeks. The persons treated with eleuthero showed a significant increase of the total number of immune-competent cells (P<0.0001), including lymphocytes (predominantly cells T, cells T-supporters/inducer and natural killers). A significant increase of cells T, also activated, was also observed (P<0.01). A fraction of polysaccharids of eleuthero roots increased the activity of cell killers activated by lymphochines and improved the activities of cell killers stimulated by interleukine 2, in vitro. An extract of roots increased the phagocytosis o Camdida albicans by human granulocytes and moncytes, in vitro, by 30 – 45%. A fraction of polysaccharids stimulated the lymphocytic phagocytosis that depend on cells T of the lymphocytes B, in vitro. This fraction, by intraperitoneal administration, increased significantly the counting of cells that form plaques, and the phagocytic activity of lymphocytes. Furthermore, increased the level of anti-bovine IgA.

4. Antiviral Activity

In vitro, the ethanolic extract inhibits the replication of the human rhinovirus, the syncytal respiratory virus, and the influenza virus A. In life studies, the extract has shown antiviral activity in mice against the influenza A virus when administered by intranasal way. Furthermore, and by intraperitoneal administration, it inhibits the virus of the vesicular stomatitis, probably for the formation of gamma-interferon.

5. Antioxidant Activity

The watery extract shows an antioxidant activity in vitro, during 5 different experimental methods.

6. Hepatic-Protection

Its contents of lignanos (Eleutherosids B, D, and E) improve the hepatic function and contribute to metabolize toxic substances and medicaments like barbitures and chemotherapist agents. At dosages of less than 500 mg./kg., the watery extract shows a hepatic-protective action against the administration of paracetamol and carbon tetrachloride.

7. Antineoplasic Activity

In vitro, the watery extract of eleutherococo root shows a cytotoxic effect on leukemic cells. It improves the effectivity of chemo and radiotherapy and also reduces its secondary effects and contributes to a fast recovery of the bone marrow.

8. Cardiovascular Action

The eleutherosid B1 (isofraxidine, isofraxidine glucosid) and the eleutherosids D and E (syringoresinol heterosids) show an anti-aggregant plateletary activity, similar to aspirin. In vitro, an extract of the roots inhibits de plateletary aggregation, induced by ADP to the human blood. A comparative study with athletes showed a reduction of the sanguine coagulation. Eleutheron increases the perfusion of ischemic and attacked miocardic areas. Furthermore, it accelerates the regeneration of all affected tissues and the recovery after surgery.

9. Hypoglycemiant

The root of eleutherococo produces a decrease of glycemia in life tests on animals. The daily intragastric administration of eleutheron (80 – 320 mg./kg of weight) during 3 days decreased the glycemia in mice by 65 – 60%, compared with placebo. This reduction is apparently due to the glucose consumption caused by the increase of the glycogene synthesis and ATP.

Some of its active compounds reduce the process of glycolization of the proteins and therefore reduce the deterioration caused by this process like, e. g., the neuropathy and other complications of diabetes mellitus.

10. Other Uses

Fibromialigy.

Dosage:It is recommended to take 2 to three capsules of 500 mg per day; of extract 5:1 (equivalent to 2500 mg of root powder).
Adverse Effects:Millions of Russians have taken this plant in the last decades and the Chinese since various centuries with minimum side effects at recommended dosages, and without having been reported any toxicity reactions.In a clinical study appear some few cases of insomnia, arrhythmia, and hypertonia. It may cause in some persons headaches, insomnia, nervousness, irritability, or anxiety when taken before sleeping or at high doses. One study reports that insomnia is a secondary effect.In some few cases it may cause arrhythmia, tachycardia, or an increase of arterial tension.In a study on 55 patients with rheumatic valvulopathies, 2 patient experienced arterial hypertension, headaches, and pericardial pain. Rarely may appear gastrointestinal disorders, breast pain, eruptions, asthma crisis, palpitations or uterous hemorrhage post-menopause.Medicinal InteractionIncreases the effects of plaquetary antiaggregants and oral hypoglycemiants.
Precautions:Not recommendable for persons with uncontrolled arterial hypertension.Persons who present any emergencies, like heart or cerebral attack, should not use this plant. As it reduces the glycemia, patients with diabetes should observe their glucose levels when taking this plant.It is recommended not to consume coffee while using this plant.
References

1: Drug Metab Dispos. 2003 May;31(5):519-22.Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers. Donovan JL, DeVane CL, Chavin KD. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Siberian ginseng ([SG]; Eleutherococcus senticosus) is a commonly used herbal preparation. The objective of this study was to assess in normal volunteers (n = 12) the influence of a standardized SG extract on the activity of cytochrome P450 CYP2D6 and 3A4. Probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again following treatment with SG (1 x 485 mg twice daily) for 14 days. Urinary concentrations of dextromethorphan and dextorphan were quantified, and dextromethorphan metabolic ratios (DMRs) were determined at baseline and after SG treatment. Likewise, plasma samples were collected (0-60 h) for alprazolam pharmacokinetics at baseline and after SG treatment to assess effects on CYP3A4 activity. Validated high performance liquid chromatography methods were used to quantify all compounds and relevant metabolites. There were no statistically significant differences between pre- and post-SG treatment DMRs indicating a lack of effect on CYP2D6 (P > 0.05). For alprazolam there also were no significant differences in the pharmacokinetic parameters determined by noncompartmental modeling (C(max), T(max), area under the curve, half-life of elimination) indicating that SG does not significantly induce or inhibit CYP3A4 (P > 0.05). Our results indicate that standardized extracts of SG at generally recommended doses for over-the-counter use are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination.

Publication Types:•  Clinical Trial
2: Phytother Res. 2000 Feb;14(1):30-5.The influence of active components of Eleutherococcus senticosus on cellular defence and physical fitness in man. Szolomicki J, Samochowiec L, Wojcicki J. Department of Experimental and Clinical Pharmacology, Pomeranian University School of Medicine, Szczecin, Poland.
The influence of active components of Eleutherococcus senticosus, contained in Taiga Wurzel preparation, were studied on cellular defence and physical fitness in man. 50 healthy volunteers of both sexes were selected, and basic clinical examination and laboratory tests were performed in all subjects. All were randomly subdivided into two study groups: group A with 35 subjects receiving Taiga Wurzel and group B with 15 subjects receiving Echinacea. 20 healthy males were randomly selected from both groups and underwent an ergospirometric study. The preparations were administered for 30 days as follows: Taiga Wurzel 25 drops three times daily, Echinacea 40 drops three times daily. After 1 month blood was drawn for control tests. Changes in the following blood parameters were observed in comparison to initial values in group A: total and LDL cholesterol, triglycerides and glucose. No alterations were seen in group B . The ergospirometric test revealed a higher oxygen plateau in group A (Taiga Wurzel) On the basis of the present study the following conclusions were drawn: active components in Eleutherococcus senticosus contained in Taiga Wurzel preparation affect cellular defence and physical fitness, as well as lipid metabolism.
Publication Types:•  Clinical Trial•  Randomized Controlled Trial---3: Arzneimittelforschung. 1987 Oct;37(10):1193-6.
Flow-cytometric studies with eleutherococcus senticosus extract as an immunomodulatory agent. Bohn B, Nebe CT , Birr C. Orpegen Medizinisch-Molekularbiologische Forschungsgesellschaft mbH, Heidelberg , Fed. Rep. of Germany .A placebo-controlled study of the effect of an Eleutherococcus senticosus extract (Eleukokk) on the immune system was performed with 36 healthy volunteers utilising quantitative multi-parameter flow cytometry with monoclonal antibodies directed against specific surface markers of human lymphocyte subsets. Volunteers in the verum group received 10 ml of an ethanolic (vincamine free) eleutherococcus senticosus preparation, 3 times daily for 4 weeks. In the placebo, the eleutherococcus extract was substituted by additional wine, resulting in identical final concentrations of ethanol in both preparations. The purpose of the double-blind study was the demonstration of possible effects on the cellular immune status, as determined by quantitative flow cytometry.The most salient feature in the verum group was a drastic increase in the absolute number of immunocompetent cells, with an especially pronounced effect on T lymphocytes, predominantly of the helper/inducer type, but also on cytotoxic and natural killer cells. In addition, a general enhancement of the activation state of T lymphocytes was observed. No side effects were observed during the trial or afterwards (observation period 6 months).

Publication Types:•  Clinical Trial•  Controlled Clinical Trial•  Randomized Controlled Trial 
4: Planta Med. 2004 Jun;70(6):564-6.Platelet anti-aggregating triterpenoids from the leaves of Acanthopanax senticosus and the fruits of A. sessiliflorus. Jin JL, Lee S, Lee YY. Natural Products Research Institute, Seoul National University , Seoul , Korea .
Six triterpenoids, chiisanogenin, chiisanoside, ursolic acid, oleanolic acid, beta-sitosterol and daucosterol, were isolated as the platelet anti-aggregating components from the leaves of Acanthopanax senticosus and the fruits of A. sessiliflorus. Chiisanogenin showed about 50-fold higher potency than acetylsalicylic acid (ASA) on U46619-induced platelet aggregation (IC50o:6.21 microM) and 10-20-fold higher effects than ASA on epinephrine- and arachidonic acid (AA)-induced aggregation (IC50:2.50 and 4.81 microM, respectively).
5: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Jan;24(1):55-8.[Experimental study on anti-tumor effects of cortex Acanthopanacis senticosus in vivo and in vitro] Shan BE, Li QX, Liang WJ. Scientific Center, Fourth Hospital , Hebei Medical University, Shijiazhuang
OBJECTIVE: To provide a basis for development and preparation of the new anti-tumor agents from Cortex Acanthopanacis senticosus (CAS), through isolating the active substances from CAS and studying the anti-tumor effect of CAS extracts in vivo and in vitro. METHODS: The effects of CAS extracts and its isolated ingredients on tumor cell proliferation in vitro was determined by 3H-TdR incorporation; the anti-tumor component of CAS was isolated and purified by chromatography; the tumor bearing mice model was established by injecting tumor cell subcutaneously, and the model was used to observe the anti-tumor effect of CAS extract administered through gastrogavage. RESULTS: CAS extract showed obvious inhibition on tumor cell proliferation originated from multiple tissues (P < 0.01) and displayed a better dose-effect relationship . After orally taken CAS extract, the general condition of mice in the experimental group were better than that in the untreated control group, revealing a slower growth and significantly prolonged survival period (P < 0.01). A protein component, having inhibitory effect on tumor cell proliferation and the molecular weight was 64 kda, it was isolated by the thin layer gel chromatography. CONCLUSION: CAS has not only the in vitro inhibitory effect on cell proliferation of multiple kinds of tumor, but also a good anti-tumor effect in vivo. The anti-tumor activity of CAS is correlated with a protein component with the molecular weight of 64 kda. Further isolation, purification, study on mechanism will provide scientific evidence for clinical application and development of CAS in anti-tumor effect.
6: J Ethnopharmacol. 2004 Aug;93(2-3):247-53.Anti-metastatic activity of Acanthopanax senticosus extract and its possible immunological mechanism of action. Yoon TJ, Yoo YC, Lee SW. Department of Food Science and Biotechnology, Kyonggi University, Kyonggido 442-760, Republic of Korea.
Antitumor and immunomodulatory activities of an aqueous extract (GF100) of Acanthopanax senticosus were examined. In experimental lung metastasis of colon26-M3.1 carcinoma cells, intravenous (i.v.) administration of GF100 2 days before tumor inoculation significantly inhibited lung metastasis in a dose-dependant manner. The i.v. administration of GF100 also exhibited the therapeutic effect on tumor metastasis of colon26-M3.1 cells, when it was injected 1 day after tumor inoculation. In an in vitro cytotoxicity analysis, GF100 at the concentration up to 1000microg/ml did not affect the growth of colon26-M3.1 cells. In contrast, GF100 enhanced the responsiveness to a mitogen, concanavalin A (ConA), of splenocytes in a dose-dependent manner.Peritoneal macrophage stimulated with GF100 produced various cytokines such as IL-1beta, TNF-alpha, IL-12 and IFN-gamma in an in vitro experiment. The macrophages obtained from the mice which were injected with GF100 (500microg) 3 days before the assay showed significantly higher tumoricidal activity against tumor cells than that of the untreated macrophages . In addition, the i.v. administration of GF100 significantly augmented NK cytotoxicity to Yac-1 cells. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of GF100 on lung metastasis of colon26-M3.1 cells.These data suggest that GF100 has antitumor activity to inhibit tumor metastasis prophylactically as well as therapeutically, and its antitumor effect is associated with activation of macrophages and NK cells. 
7: Arch Pharm Res. 2004 Feb;27(2):217-24.Anti-metastatic activity of glycoprotein fractionated from Acanthopanax senticosus, involvement of NK-cell and macrophage activation. Ha ES, Hwang SH, Shin KS. Department of Food Science and Biotechnology, Kyonggi University , Kyonggido 442-760, Korea .
Previously, we reported that water-extracted Acanthopanax senticosus exhibited anti-metastatic activity by stimulating the immune system. In this study, we fractionated glycoproteins (EN-SP) from the soluble protein layer (GF-AS) of A. senticosus and determined their basic chemical properties. We also investigated the anti-tumor and immunostimulating activities of the fractionated glycoprotein, EN-SP. We found that intravenous (i.v.) administration of GF-AS dramatically inhibited metastasis of colon26-M3.1 carcinoma cells to the lung in a dose-dependent manner. In vitro analysis showed GF-AS to enhance the proliferation of splenocytes. GF-AS also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-1beta, TNF-alpha, IL-12 and IFN-gamma. Furthermore, the production of these cytokines was partially blocked when peritoneal macrophage was cultured with the polyclonal antibodies against GF-AS. The depletion of NK cells by rabbit anti-asialo GM1 serum partly abolished the inhibitory effect of GF-AS on lung metastasis of colon26-M3.1 cells. Using gel filtration, EN-SP, an active glycoprotein fraction, is isolated from GF-AS. While both GF-AS and EN-SP stimulated the proliferatation of splenocytes of normal mice, EN-SP showed higher anti-metastatic activity and more potently stimulated the proliferation of splenocytes compared to GF-AS. These results suggest the use of EN-SP, the fractionated glycoprotein from A. senticosus, can be used as a therapeutical reagent to prevent or inhibit tumor metastasis. 
8: Phytother Res. 2000 Nov;14(7):489-94.Antioxidant and hepatoprotective effects of Acathopanax senticosus. Lin CC, Huang PC. Graduate Institute of Natural Products, Kaohsiung Medical College , Kaohsiung , Taiwan .
Acathopanax senticosus (Rupr. et Maxim.) Harms. is a popular folk medicine used as a nutrient for hepatitis and cancer in Taiwan . In this study, the antioxidant activity of the crude extract and the hepatoprotective activities on CCl(4)- or acetaminophen-induced toxicity in the rat liver were evaluated. Our results suggest that A. senticosus exerts some antioxidant effects. On a CCl(4)- or acetaminophen-intoxicated -model, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased by CCl(4) or acetaminophen administration and reduced by treatment with the plant extract. Histological changes around the hepatic central vein were also recovered by treatments. However, treatments with larger doses of the crude extract of A. senticosus enhanced liver damage. This result suggests that even if A. senticosus had hepatoprotective activity in small doses , treatment with larger doses would possibly induce some cell toxicity.
9: Arch Pharm Res. 2004 Jan;27(1):106-10.Anti-oxidant activities of Acanthopanax senticosus stems and their lignan components. Lee S, Son D, Ryu J. Natural Products Research Institute and College of Pharmacy , Seoul National University , Seoul 110-460, Korea .
The antioxidant activities of Acanthopanax senticosus stems were evaluated in CCl4-intoxicated rats. The n-butanol fraction from the water extract of the stems, when pretreated orally at 200 mg/kg/day for 7 consecutive days in rats, was demonstrated to exhibit significant increases in antioxidant enzyme activities such as hepatic cytosolic superoxide dismutase, catalase and glutathione peroxidase by 30.31, 19.82 and 155%, respectively. The n-butanol fraction whereas showed a significant inhibition of serum GPT activity (65.79% inhibition) elevated with hepatic damage induced by CCl4-intoxication . Eleutheroside B, a lignan component, isolated from the n-butanol fraction was found to cause a moderate free radical scavenging effect on DPPH, its scavenging potency as indicated in IC50 value, being 58.5 microM. These results suggested that the stems of A. senticosus possess not only antioxidant but also hepatoprotective activities.10: Basic Clin Pharmacol Toxicol. 2004 Jun;94(6):298-304.Water-Soluble Polysaccharide from Eleutherococcus senticosus Stems Attenuates Fulminant Hepatic Failure Induced by D-Galactosamine and Lipopolysaccharide in Mice. Park EJ, Nan JX, Zhao YZ. Department of Pharmacy, Wonkwang University , Iksan, Jeonbuk 570-749, Republic of Korea .The aim of this study was to investigate whether Eleutherococcus senticosus stems could attenuate D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. E. senticosus, known as Siberian ginseng, is a popular folk medicine used as a tonic in Asia . Preparations of E. senticosus used in this study were as follows; (i) 70% ethanol extract (ii) water extract (iii) ethanol-soluble part of the water extract (iv) polysaccharide obtained as an 80% ethanol insoluble of the water extract. Preparations were given by intraperitoneal (300 mg/kg and 50 mg/kg) or oral (300 mg/kg) injection at 12 hr and 1 hr before a D-galactosamine / lipopolysaccharide injection. The intraperitoneal injection of water extract and polysaccharide significantly lowered serum levels of tumour necrosis factor-alpha, aspartate transaminase and alanine transaminase, improved the histologic changes in liver, inhibited hepatocyte apoptosisconfirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay, and suppressed the lethality induced by D-galactosamine/lipopolysaccharide . The oral administration of water extract and polysaccharide also reduced serum aspartate transaminase, alanine transaminase and tumour necrosis factor-alpha levels. In contrast 70% ethanol extract and ethanol-soluble part of the water extract had no protective effect when treated intraperitoneally or orally. These results indicate E. senticosus stems attenuate fulminant hepatic failure induced by D-galactosamine / lipopolysaccharide in mice and the protective effect is due to water-soluble polysaccharides in E. senticosus stems.
11: Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):473-80.Vascular effects of Siberian ginseng (Eleutherococcus senticosus): endothelium-dependent NO- and EDHF-mediated relaxation depending on vessel size. Kwan CY, Zhang WB, Sim SM. HSC-4N40, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Siberian ginseng (SG) has been widely and historically consumed as a health food product for the improvement of self well-being, but whether vascular relaxation may contribute to such a therapeutic health effect has not been studied. We therefore investigated the vasorelaxant effect of the aqueous extract of the roots of SG (Eleutherococcus senticosus Maxim) using several in vitro vascular rings prepared from dog carotid artery, rat aorta and rat mesenteric artery. SG extract (0.04-0.8 mg/ml) caused concentration-dependent relaxation in dog carotid arterial rings pre-contracted with 100 microM phenylephrine (PE), and the relaxation was primarily endothelium-dependent . Treatment with 100 microM L-NOARG (a nitric oxide synthase inhibitor) either prevented or totally reverted SG-induced relaxation, suggesting that the endothelium-dependent relaxation was mediated by NO . Similar endothelium-dependent vascular relaxant responses were also obtained with rat aortic and mesenteric arterial rings , except that it occurred over a relatively higher concentration range of SG (0.5-2.0 mg/ml). When tested in the presence of 300 microM L-NAME, the vasorelaxant effect of SG was inhibited totally in rat aorta but only partially in rat mesenteric artery. The relaxation to SG that was insensitive to L-NAME in rat mesenteric arterial rings was eliminated when the rings (both proximal and distal ends) were pre-treated with a combination of 300 microM L-NAME and 15 mM KCl indicating the involvement of endothelium-derived hyperpolarizing factor (EDHF). This vasorelaxant response of the SG extract was inhibited partially by atropine (1 microM), completely by TEA ( 5 mM ), but not by indomethacin (1 microM) or propranolol (10 microM). SG up to 2 mg/ml had no effect on KCl-induced contraction in any of the vascular rings studied. When compared with carbachol-induced (CCh) relaxation, SG resembles CCh in that the sensitivity to L-NAME inhibition is dependent on vascular size, i.e. aorta >proximal end of mesenteric artery >distal end of mesenteric artery. However, SG exhibited different potencies to relaxation while CCh showed similar potency (EC(50) of about 0.2 microM) in all three vascular segments. In conclusion, we have demonstrated that the vascular effect of SG is endothelium-dependent and mediated by NO and/or EDHF depending on the vessel size. Other vasorelaxation pathways, such as inhibition of K(+)-channels and activation of muscarinic receptors, may also be involved.
12: Phytother Res. 2004 Feb;18(2):160-3.Effect of Acanthopanax senticosus on lipoprotein lipase in 3T3-L1 adipocytes. Yang JY, Lee KS, Kim MK. Department of Biochemistry, Chonbuk National University Medical School , Jeonju , Korea .
The effect of Acanthopanax senticosus (AS) leaves on lipoprotein lipase (LPL) was investigated in 3T3-L1 adipocytes. A water extract of AS leaves increased the LPL activity in culture medium of adipocytes in a dose- and time-dependent manner. The AS extract contained heparin-like LPL releasing components, however, the increase of medium LPL activity was continued up until 12 h, in contrast to the rapid decline after heparin treatment. The increase of LPL mRNA was also observed after AS extract treatment, suggesting that LPL induction occurs at the transcriptional level. The AS extract could partially reverse the LPL suppression by tumour necrosis factor-alpha in 3T3-L1 adipocytes. These results of an AS extract-induced increase of LPL activity in vitro suggest the possible action of AS as a facilitator of plasma triglyceride clearance.13: Pol J Vet Sci. 2003;6(3 Suppl):37-9.The influence of Eleuterococcus senticosus on cellular and humoral immunological response of mice. Rogala E, Skopinska-Rozewska E, Sawicka T. Department of Laboratory Diagnostic and Immunology, National Instutute of Tuberculosis and Lung Diseases, Warsaw , Poland .
The influence of Eleuterococcus senticosus on cellular and humoral immune response was evaluated. The experiments were performed on animal models (Balb/c mice and F1 crossbreeds Balb/cxC3H). It was shown that Eleuterococcus has immunomodulatory properties. This substance enhanced the cellular response of the mouse immunological system (chemokinetic activity of mice spleen cells, GvH reaction ). A stimulatory effect of Eleuterococcus on the humoral response (antibody production) was also observed . Eleuterococcus did not augment the angiogenic activity of human renal carcinoma cells.
14: Am J Chin Med. 2003;31(3):379-88.Protective effect of Acanthopanax senticosus against ethanol-induced apoptosis of human neuroblastoma cell line SK-N-MC. Jang MH, Shin MC, Kim YJ. Department of Physiology, College of Medicine , Kyung Hee University , Seoul , Korea .
The protective effect of Acanthopanax senticosus (AS) against ethanol (EtOH)-induced apoptosis of the human neuroblastoma cell line SK-N-MC was investigated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, DNA fragmentation assay, reverse transcription-polymerase chain reaction (RT-PCR), and caspase-3 assay. It was shown that cells treated with EtOH exhibit classical apoptotic features, while cells pre-treated with Acanthopanax senticosus prior to EtOH exposure showed decreased occurrence of apoptotic features . In addition, Acanthopanax senticosus pre-treatment was shown to inhibit EtOH-induced increase in caspase-3 mRNA expression and activity. These results suggest that Acanthopanax senticosus may exert a protective effect against EtOH-induced apoptosis of human neuroblastoma cells. 
15: Planta Med. 2003 Jul;69(7):610-6.In vivo anti-inflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus. Jung HJ, Park HJ, Kim RG. Division of Applied Plant Sciences, Sangji University , Woosan-Dong, Wonju , Korea .
In the present study, liriodendrin isolated by activity-guided fractionation from the ethyl acetate (EtOAc) extracts of the stem bark of Acanthopanax senticosus, was evaluated for anti-inflammatory and antinociceptive activities. Liriodendrin (5, 10 mg/kg/day, p. o.) significantly inhibited the increase of vascular permeability induced by acetic acid in mice and reduced an acute paw edema induced by carrageenan in rats. When the analgesic activity was measured by the acetic acid-induced writhing test and hot plate test, liriodendrin showed a dose-dependent inhibition in animal models. In addition, syringaresinol, the hydrolysate of liriodendrin, more potently inhibited the LPS-induced production of NO, PGE 2 and TNF-alpha production of macrophages than liriodendrin. Consistent with these observations, the expression level of iNOS and COX-2 enzyme was decreased by syringaresinol in a concentration-dependent manner. These results suggest that the anti-inflammatory and antinociceptive effects of liriodendrin after oral administration were attributable to the in vivo transformation to syringaresinol, which may function as the active constituent. 
Journal Cover16: Int Immunopharmacol. 2003 Sep;3(9):1301-12.Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus. Han SB, Yoon YD, Ahn HJ. Biopotency Evaluation Laboratory, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Oundong, Yusong, Taejon 305-333, South Korea .
We investigated the mechanism of the immunomodulatory action of polysaccharide (ASP) isolated from a cell culture of Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and cytokine production of T cells. Since ASP cannot penetrate the cell membrane due to its large molecular mass, such cellular activation may be caused by the surface binding of ASP to receptors expressed on B cells and macrophages. The possibility that TLRs, which are known to be involved in immune-related responses, may be the receptor(s) of ASP was investigated. The immunomodulating activities of ASP on the B cells and macrophages of C3H/HeJ mice, expressing a defective toll-like receptor (TLR)-4, were decreased versus the corresponding cells from C3H/HeN mice. In addition, the activities of ASP on B cells and macrophages were significantly reduced by treating the cells with antibodies to TLR4 and TLR2 prior to ASP, suggesting that both of them are the possible receptors of ASP. The ligation of TLRs induced by ASP was able to activate mitogen-activated protein kinases (MAPKs), such as Erk1/2, p38 and JNK, and the transcription factor NF-kappaB. Although ASP was shown to activate the TLR signaling cascades in the same manner as lipopolysaccharide (LPS), these two could be differentiated by the finding that polymyxin B (PMB), a specific inhibitor of LPS, did not significantly affect the activities of ASP on B cells and macrophages. Taken together, our results demonstrate that ASP, isolated from a cell culture of A. senticosus, activates B cells and macrophages by interacting with TLRs and leading to the subsequent activation of mitogen-activated protein kinases and NF-kappaB. 
Journal Cover17: Toxicol In Vitro. 2003 Apr;17(2):229-36.Intraspecific relationship analysis by DNA markers and in vitro cytotoxic and antioxidant activity in Eleutherococcus senticosus. Yu CY, Kim SH, Lim JD. Division of Applied Plant Sciences, College of Agriculture and Life Sciences, Kangwon National University, Chunchon 200-701, South Korea.
To analyse genetic relationships and intraspecific variation within Eleutherococcus senticosus, the polymerase chain reaction (PCR) was performed on total genomic DNAs of 10 Eleutherococcus collections. Ten primers were used for amplification, yielding 106 bands, of which 87 were polymorphic. The genetic diversity and genetic distance among 10 collections of Eleutherococcus species were used to describe the dendrogram showing the phylogenic relationship. The 10 collections were classified into two groups (groups I and II) at a similarity coefficient of 0.50. Group I included E. senticosus from Bukhaedo (Japan), E. sessliliflorus from Youngwal (Korea), E. seoulense and E. chiisanesis, while group II included several internal and Russian collections. The range of polymorphism was from 66.7 to 90.9% in the 87 amplified polymorphic DNA fragments. The similarity value of all collections ranged from 0.41 to 0.92, and the average genetic distance was 0.61. Thus, RAPD analysis was useful in determining genetic relatedness among collections and in identifying different genotypes of E. senticosus and other Eleutherococcus species. Also, the biological activity on DPPH radical scavenging, antilipid peroxidation in rat liver microsomes and cytotoxic sulforhodamine B (SRB) assay was evaluated using root extracts of E. senticosus, Odaesan , Korea . Ethyl acetate and n-butanol fractionationrevealed strong antioxidant against scavenging on DPPH free radical and also ethyl acetate fractionation exhibited high antilipid peroxidative activities. In the cytotoxic effects were evaluated on seven human cancer cell lines, the values of 50% growth inhibition (GI(50)) were mostly below 30 microg/ml for crude extracts to be considered as significantly active. 
18: J Nat Prod. 1986 Mar-Apr;49(2):293-7.Isolation and hypoglycemic activity of eleutherans A, B, C, D, E, F, and G: glycans of Eleutherococcus senticosus roots. Hikino H, Takahashi M, Otake K, Konno C.
Intraperitoneal injection of an aqueous extract of the crude drug “shigoka” (Siberian ginseng), Eleutherococcus senticosus roots, remarkably diminished plasma-sugar level in mice. Fractionation of the extract by monitoring the activity yielded seven glycans, eleutherans A, B, C, D, E, F, and G, which exerted marked hypoglycemic effects in normal and alloxan-induced hyperglycemic mice. 
19: J Agric Food Chem. 2003 Mar 12;51(6):1586-91.Protein glycation inhibitory and antioxidative activities of some plant extracts in vitro. Kim HY, Kim K. Food Function Research Division, Korea Food Research Institute, San 46-1 Baekhyun-dong, Bundang-gu, Songnam-si, Kyonggi-do 463-420, Republic of Korea.
The protein glycation inhibitory activity of aqueous ethanolic extracts from 25 plant tissues was evaluated in vitro using the model system of bovine serum albumin and fructose. The most bioactive plant tissue was Allium cepa (skin), followed by Illicium religiosum (bark and wood), Fagopyrum esculentum (hull), Origanum officinalis (leaf), Rosmarinus officinalis (leaf), Pyrus pyrifolia (bark), Acanthopanax senticosus (bark), Eugenia caryophllata (leaf), and Erigeron annuus (whole). The extracts with glycation inhibitory activity also showed antioxidative activity when a micellar linoleic acid peroxidation system was applied followed by 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization and 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assays. The glycation inhibitory activity was significantly correlated with the antioxidative potency of the extracts. The positive glycation inhibitory and antioxidative activities of these plants might suggest a possible role in targeting aging and diabetic complications. 
20: Acta Pol Pharm. 2002 Sep-Oct;59(5):395-401.Estimation of humoral activity of Eleutherococcus senticosus. Drozd J, Sawicka T. Department of Biological Preparations, Drug Institute, Warszawa.The aim of the present work was an estimation of the influence of two plant pharmaceutical preparations containing an extract from the root of Eleutherococcus senticosus: Argoeleuter tablets and Immuplant tablets, on the humoral response of immunological system. Experiments were performed with female Balb/c mice six weeks old. In order to reveal the influence of taking preparations, containing an extract from Eleutherococcus senticosus on some elements of the immunological system, three ways of their administration have been compared: before illness, during illness and a combination of both. The obtained results allow formulating the following conclusions: – the pharmaceutical preparations, containing the extract from Eleutherococcus senticosus administered orally, influence on the increase of the level of immunoglobulins comprised in the mice’s blood serum, – the pharmaceutical preparations act with different power, not fully dependent on the content of marker of the active substance – eleutheroside E, – dosage of the preparations containing the extract from Eleutherococcus senticosus should not be established basing only on the extract content, – best curative results, measured as the stimulation of humoral response of the organism were obtained when a given preparation was administered therapeutically, even though the combined administration – prophylactically with prolonged administration during illness also is correct.
21: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001 Feb;21(2):105-7.Effect of Acanthopanax senticosus injection on plasma and urinary endothelin in early stage of diabetic nephropathy Ni HX, Luo SS. Department of Endocrinology, Zhejiang Provincial Hospital of TCM, Hangzhou .OBJECTIVE: To explore the mechanism of Acanthopanax senticosus (AS) on diabetic nephropathy (DN) patients by observing its effect on urinary albumin excretion (UAE) and renal endothelin (ET) metabolism. METHODS: Forty-seven patients of diabetes mellitus (DM) type 2 with persistent microalbuminuria and normotension were randomly divided into two groups, the conventional treatment group (control group) and the AS treatment group. The treatment course was 8 weeks. The changes of UAE, plasma and urinary ET levels before and after treatment were observed. RESULTS: Levels of UAE, plasma and urinary ET lowered significantly (P < 0.01) in the AS groups, while no significant change was shown in the control group. By correlation analysis, the decrement of UAE was positively correlated with the decrement of urinary and plasma ET levels (r = 0.72, P < 0.01 and r = 0.63, P < 0.01). CONCLUSION: The protective effect of AS injection on DN is probably correlated with its inhibition on ET synthesis in kidney.
22: Arch Pharm Res. 2003 Jan;26(1):40-2.Antibacterial compounds from the leaves of Acanthopanax senticosus. Lee S, Shin DS, Oh KB. Natural Products Research Institute and College of Pharmacy , Seoul National University , Seoul 110-460, Korea .
Chiisanogenin (1), hyperin (2) and chiisanoside (3) were isolated from the leaves of Acanthopanax senticosus, and were tested for their inhibitory activities against 6 strains of bacteria. Among them, chiisanogenin (1) revealed broad but moderate antibacterial activities against G (+) and G (-) bacteria , the minimum inhibitory concentration (MIC) being in the range of 50-100 microg/ml.
23: Phytother Res. 2002 Aug;16(5):474-8.Effect of Acanthopanax senticosus Harms on biogenic monoamine levels in the rat brain. Fujikawa T, Soya H, Hibasami H. Department of Biochemistry, Mie University Faculty of Medicine, Tsu, Mie 514-8507, Japan .
The extract of the stem bark of Acanthopanax senticosus Harms (ASH) is known to have healing and protective effects on stress-induced disturbance of mental status. We have analysed whether a single or chronic (2 week) administration of ASH can affect concentrations of noradrenaline (NA), dopamine (DA) and their metabolites in the normal rat brain. A single p.o. administration of ASH elevated the NA and DA levels in the whole brain of rats in a dose-dependent manner. A single or 2 week administration of ASH (500 mg/kg) showed a marked increase in the DA level only in the striatum. However, NA levels were increased by a single dose of ASH in a wide range of brain regions such as the cortex, hypothalamus, striatum, hippocampus, substantia nigra and pons. When administered for 2 weeks no increase in NA levels was seen in these brain regions, except for an increase in the frontal cortex and anterior hypothalamus. The present results suggest that ASH may act by regulating NA and DA levels in specific brain regions related to stress response and Parkinson’s disease.24: Wei Sheng Yan Jiu. 1998 Nov 30;27(6):421-4.[Effect of Ciwujia (Radix Acanthopanacis senticosus) preparation on exercise performance under constant endurance load for elderly] Wu Y, Wang X, Li M, Compbell TC. Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine, Beijing 100050, China .The effect of Ciwujia (Radix Acanthopanacis senticosus) preparation on human exercise performance was investigated by using 13 healthy volunteers aged 50-57. Under constant endurance load with 450 kg .m/min (75 W), the respiratory quotient after taking Ciwujia preparation was reduced to 0.88 from 0.96, which implied that the utilization of lipid increased with 27.2% as energy fuel during exercise. Meanwhile, the heart rate was reduced with 8.7%, and O2 uptake per heart beat increased with 16.18%. All results indicated that the Ciwujia preparation could increase O2 uptake, spare the glycogen in muscle and improve the exercise endurance and work performance in human subjects.
25: J Ethnopharmacol. 2002 Mar;79(3):347-52.Effect of Acanthopanax senticosus stem on mast cell-dependent anaphylaxis. Yi JM, Hong SH, Kim JH. Department of Oriental Pharmacy, College of Pharmacy, Korea Institute of Oriental Pharmacy, Wonkwang University , Iksan, Chonbuk 570-749, South Korea .
We studied the effect of Acanthopanax senticosus stem (ACPS) on mast cell-dependent anaphylaxis. ACPS inhibited compound 48/80-induced systemic anaphylaxis at a dose of 1.0 g/kg by 50%. ACPS also inhibited passive cutaneous anaphylaxis reaction and histamine release from mast cells in a dose-dependent manner, respectively. Moreover, ACPS had an inhibitory effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from mast cells. These results indicate that ACPS inhibits mast cell-mediated anaphylaxis in vivo and in vitro murine model .
Journal Cover26: Clin Chim Acta. 2001 Oct;312(1-2):163-8.Acanthopanax senticosus root inhibits mast cell-dependent anaphylaxis. Yi JM, Kim MS, Seo SW. Department of Oriental Pharmacy, College of Pharmacy and Center of Oriental Medicinal Science, Wonkwang University, Chonbuk, 570-749, Iksan City, South Korea.
BACKGROUND: Mast cells synthesize and secrete chemical mediators which play a central role in anaphylaxis. METHODS: The effect of Acanthopanax senticosus root (ASR) on mast cell-dependent anaphylaxis was investigated. RESULTS: ASR inhibited induced systemic anaphylactic shock at the dose of 1.0 g/kg by 50%. When ASR was given as pre-treatment at concentrations ranging from 0.01 to 2.0 g/l, the histamine release from rat peritoneal mast cells induced was reduced in a dose-dependent manner. ASR (2.0 g/kg) also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE to 53.17+/-6.62%. Moreover, ASR inhibited tumor necrosis factor-alpha production in a concentration-dependent manner, and the treatment of 1 g/l blocked the production by 32.5+/-3.50% compared to saline value. CONCLUSIONS: ASR may possess effective anti-anaphylactic activity. 
27: J Pharm Sci. 1992 Jul;81(7):661-2.Ciwujianosides D1 and C1: powerful inhibitors of histamine release induced by anti-immunoglobulin E from rat peritoneal mast cells. Umeyama A, Shoji N, Takei M. Faculty of Pharmaceutical Sciences, Tokushima Bunri University , Japan .
In rat peritoneal mast cells induced by anti-immunoglobulin E, ciwujianosides D1 (1) and C1 (2) from Acanthopanax senticosus (ciwujia) strongly inhibited histamine release in a concentration-dependent manner. The inhibitory effect of 1 was approximately 6800 times stronger than that of disodium cromoglycate.28: Acta Pharmacol Sin. 2001 Dec;22(12):1057-70.Constituents and pharmacological effects of Eucommia and Siberian ginseng. Deyama T, Nishibe S, Nakazawa Y. Central Research Laboratories, Yomeishu Seizo Co Ltd, Minowa-Machi, Kamiina-Gun, Nagano 399-4601, Japan .The bark and leaves of Eucommia ulmoides Oliv (Eucommiaceae) and “Siberian ginseng” (Ezoukogi in Japanese) prepared from the root bark or stem bark of Eleutherococcus senticosus Maxim (Acanthopanax senticosus Harms) have been used as tonic and anti-stress drug. The extracts of Eucommia showed anti-hypertensive, anti-complementary, anti-oxidative, and anti-gastric ulcer effects, and promoting collagen synthesis, accelating granuloma formation, and other pharmacological effects. The Siberian ginseng exhibited anti-fatigue, anti-stress, immuno-enhancing effect, CNS activity, and anti-depressive effect. By now, 40, 28, and 10 compounds have been isolated from Eucommia ulmoides bark, Eucommia ulmoides leaves, and Siberian ginseng, respectively, and their structures were elucidated. Their pharmacological activities were mainly due to lignans and iridoid glycosides.Publication Types:•  Review

•  Review, Tutorial

 

Journal Cover29 : Antiviral Res. 2001 Jun;50(3):223-8.Antiviral activity of an extract derived from roots of Eleutherococcus senticosus. Glatthaar-Saalmuller B, Sacher F, Esperester A. Labor Dr. Glatthaar, Virologische Testsysteme, Gewebekulturen, Immundiagnostik, Biotechnologie Zentrum Tubingen/Reutlingen, Reutlingen, Germany.
A liquid extract from Eleutherococcus senticosus roots inhibited the productive replication of human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus in cell cultures infected with these viruses, all of which belong to the RNA type viruses. Analysis of virus production after treatment of the infected cells using plaque-reduction assays showed a strong antiviral activity of the Eleutherococcus extract. In contrast, no effect was detected using the same protocol for cells infected with the DNA viruses, adenovirus (Adeno 5) or herpes simplex type 1 virus (HSV 1). Pre-treatment of cells did not inhibit either virus adsorption or virus replication. The results of the study demonstrate that the Eleutherococcus extract inhibited the replication of all RNA viruses studied so far. This antiviral activity remained stable under the conditions used for drug preparation and storage.Publication Types:•  Evaluation Studies
Journal Cover30: Med Hypotheses. 2001 May;56(5):567-72.Panax ginseng and Eleutherococcus senticosus may exaggerate an already existing biphasic response to stress via inhibition of enzymes which limit the binding of stress hormones to their receptors. Gaffney BT, Hugel HM, Rich PA. Department of Human Biology and Movement Science, Faculty of Biomedical and Health Sciences and Nursing, Royal Melbourne Institute of Technology Bundoora Campus, Melbourne , Australia .
A mechanism of action for Panax ginseng (PG) and Eleutherococcus senticosus (ES) is proposed which explains how they could produce the paradoxical effect of sometimes increasing and sometimes decreasing the stress response. The mechanism suggests that this biphasic effect results from increased occupancy of positive and negative feedback stress hormone receptors by their natural ligands due to inhibition of specific enzymes which function to limit receptor occupancy. Specifically, it is suggested that PG inhibits 11-beta hydroxysteroid dehydrogenase one and ES inhibits catechol- O -methyl transferase , both of which reside in close proximity to stress hormone receptors and catalyse the degradation of stress hormones into inactive compounds. In addition, it is suggested that the increased energy said to result from PG and ES may be a consequence of their increasing the occupancy of stress hormone receptors which function to redistribute the body’s energy reserves from regeneration to activity .
Publication Types:•  Review•  Review, Tutorial
31: Phytother Res. 2001 May;15(3):268-70.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. Schmolz MW, Sacher F, Aicher B. EDI (Experimental & Diagnostic Immunology) GmbH, Markwiesenstr. 55, D-72 770 Reutlingen , Germany.
An ethanol extract derived from the roots of Eleutherococcus senticosus was found to influence markedly the cytokine synthesis of activated whole blood cultures of ten healthy volunteers. Whereas the synthesis of Rantes was increased over a wide range of concentrations, the release of IL-4, IL-5 and IL-12 was significantly inhibited. An inhibition at higher concentrations, switching to a stimulation at lower doses of the extract was seen with G-CSF, IL-6 and IL-13. From these particular immuno-pharmacological effects of Eleutherococcus senticosus we suggest this herbal preparation possesses immuno-modulatory potency, rather than just being immuno-suppressive or -stimulating .
32: Arzneimittelforschung. 2001 Jan;51(1):76-83.Immunopharmacological in vitro effects of Eleutherococcus senticosus extracts. Steinmann GG, Esperester A, Joller P. Boehringer Ingelheim, Biberach/Riss, Germany .The objective of these investigations was to further elucidate the immunopharmacological profile of fluid extracts of Eleutherococcus senticosus and to identify the specific role of its characteristic eleutherosides B and E. An ethanolic dry extract of Eleutherococcus senticosus was used as starting material for the isolation of the eleutherosides B and E. Immunopharmacological studies included expression of major histocompatibility complex class I and II molecules by rat bone marrow-derived mononuclear phagocytes, human lymphocyte marker flow cytometry, and in vitro testing of human lymphocyte functions. In contrast to the isolated eleutherosides B and eleutherosides E and the re-mixed eleutherosides B and E, the whole ethanolic fluid extract of Eleutherococcus senticosus was able to induce and enhance interleukin-1 and interleukin-6 but not interleukin-2 production in vitro. The effective concentration of the whole ethanolic extract ranged from 1.0-0.1 mg/ml for the enhancement of interleuking-1 alpha production and 1.0-0.03 mg/ml for the enhancement of interleukin-6 production. It is concluded that the observed enhancing immunopharmacological activities on acute phase response mediators are best exhibited by the induction with whole ethanolic extracts whereas the species-specific and characteristic eleutherosides B and E are not associated with these activities.33: Oncol Rep. 2000 Nov-Dec;7(6):1213-6.Induction of apoptosis by Acanthopanax senticosus HARMS and its component, sesamin in human stomach cancer KATO III cells. Hibasami H, Fujikawa T, Takeda H. Faculty of Medicine, Mie University, Tsu-city, Japan.

Antitumor effect of the stem bark of Acanthopanax senticosus HARMS (ASH) from Hokkaido (Japanese name: Ezoukogi) on human stomach cancer KATO III cells was investigated. The extract of the stem bark of ASH prepared with hot water was dissolved in distilled water and used for the assay of antitumor effect on the KATO III cells. The exposure of KATO III cells to ASH led to both growth inhibition and induction of apoptosis . Morphological change showing apoptotic bodies was observed in the cells treated with ASH. The fragmentation by ASH of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. We have investigated which component in ASH is effective on the induction of apoptosis. Among chlorogenic acid, syringaresinol di-o-beta-D glucoside, syringin, and sesamin, components of the n-butanol extract prepared from ASH, sesamin suppressed the growth and induced apoptosis in the cells. These findings suggest that growth inhibition by ASH results from the apoptosis induced by sesamin, a component of ASH .

34: J Ethnopharmacol. 2000 Oct;72(3):345-93.Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look. Davydov M, Krikorian AD. Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, 11794-5215, USA .
The adaptogen concept is examined from an historical, biological, chemical, pharmacological and medical perspective using a wide variety of primary and secondary literature. The definition of an adaptogen first proposed by Soviet scientists in the late 1950s, namely that an adaptogen is any substance that exerts effects on both sick and healthy individuals by ‘correcting’ any dysfunction(s) without producing unwanted side effects, was used as a point of departure. We attempted to identify critically what an adaptogen supposedly does and to determine whether the word embodies in and of itself any concept(s) acceptable to western conventional (allopathic) medicine. Special attention was paid to the reported pharmacological effects of the ‘adaptogen-containing plant’ Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae), referred to by some as ‘Siberian ginseng’, and to its secondary chemical composition. We conclude that so far as specific pharmacological activities are concerned there are a number of valid arguments for equating the action of so-called adaptogens with those of medicinal agents that have activities as anti-oxidants, and/or anti-cancerogenic, immunomodulatory and hypocholesteroletic as well as hypoglycemic and choleretic action. However, ‘adaptogens’ and ‘anti-oxidants’ etc. also show significant dissimilarities and these are discussed. Significantly, the classical definition of an adaptogen has much in common with views currently being invoked to describe and explain the ‘placebo effect’. Nevertheless, the chemistry of the secondary compounds of Eleutherococcus isolated thus far and their pharmacological effects support our hypothesis that the reported beneficial effects of adaptogens derive from their capacity to exert protective and/or inhibitory action against free radicals. An inventory of the secondary substances contained in Eleutherococcus discloses a potential for a wide range of activities reported from work on cultured cell lines, small laboratory animals and human subjects. Much of the cited work (although not all) has been published in peer-reviewed journals. Six compounds show various levels of activity as anti-oxidants, four show anti-cancer action, three show hypocholesterolemic activity, two show immunostimulatory effects, one has choleretic activity and one has the ability to decrease/moderate insulin levels, one has activity as a radioprotectant, one shows anti-inflammatory and anti-pyretic activities and yet another has shown activity as an antibacterial agent.Some of the compounds show more than one pharmacological effect and some show similar effects although they belong to different chemical classes. Clearly, Eleutherococcus contains pharmacologically active compounds but one wishes that the term adaptogen could be dropped from the literature because it is vague and conveys no insights into the mechanism(s) of action. If a precise action can be attributed to it, then the exact term for said action should obviously be used; if not, we strongly urge that generalities be avoided. Also, comparison of Eleutherococcus with the more familiar Panax ginseng C.A. Meyer (Araliaceae), ‘true ginseng’ has underscored that they differ considerably chemically and pharmacologically and cannot be justifiably considered as mutually interchangeable. Accordingly, we recommend that the designation ‘Siberian ginseng’ be dropped and be replaced with ‘Eleutherococcus’. In the case of both Eleutherococcus and true ginseng, problems inherent in herbal preparation use include inconsistencies not only in terms of indications for use, but in the nomenclature of constituent chemical compounds, standardization, dosage and product labeling. (ABSTRACT TRUNCATED)Publication Types:•  Review•  Review, Academic35: Biol Pharm Bull. 1996 Sep;19(9):1227-30.Protective effects of Acanthopanax senticosus Harms from Hokkaido and its components on gastric ulcer in restrained cold water stressed rats. Fujikawa T, Yamaguchi A, Morita I. Faculty of Medicine, Mie University , Japan .

The aim of this study is to investigate the pharmacological effect of the stem bark of Acanthopanax senticosus Harms from Hokkaido (Japanese name: Ezoukogi) in place of the root bark as a restorative tonic on the stress-induced gastric ulcer. In the test, the extract of the stem bark of A. senticosus prepared with hot water was dissolved in water and used for the assay of the protective effect of gastric ulcer (erosion) on stressed rats that were restrained on cold water. The result from a single oral administration of the stem bark of A. senticosus-extract (50, 100 and 500 mg/kg, per day) dissolved in 1 ml distilled water did not show any protective effect on gastric ulcer, but the protective effect was observed in a dose-dependent manner from the oral administration of the extract (50, 100 and 500 mg/kg, per day) for 2 weeks. Pre-administration of the stem bark of A. senticosus-extract in a dose of 500 mg/kg showed the most potent inhibition without affecting either body or adrenal glands weights. Among ether, chloroform, n-butanol and aqueous residue extracts from the stem bark of A. senticosus-extract, the n-butanol extract used for oral administration for 2 weeks showed an obvious inhibition of 61.1% on gastric ulcer, compared with the control group which was treated with distilled water in the same way. Chlorogenic acid and syringaresinol di-o-beta-D-glucoside, as the major components of the n-butanol extract, showed a significantly inhibitory effect on gastric ulcer, at 21.4% and 51.3%, respectively. We suggested that the protective effect of the stem bark of A. senticosus on gastric ulcer may be partially due to those of chlorogenic acid and syringaresinol di-o-beta-D-glucoside.

---36: Zhongguo Zhong Yao Za Zhi. 1994 Dec;19(12):746-7, 764.

[Effects of the leaves of Acanthopanax senticosus (Rupr. et Maxim.) Harms. on myocardial infarct size in acute ischemic dogs] 

Sui DY, Lu ZZ, Ma LN, Fan ZG. Bethune University of Medical Science, Changchun .

Effects of saponin isolated from the leaves of Acanthopanax senticosus (ASS) on myocardial infarct size were studied in acute ischemic dogs. The results showed that ASS (in a dosage of 25.50 mg/kg, iv) could significantly reduce the sizes of acute myocardial infarcts and decline the serum CK and LDH activity at 6h after ligation of LAD. It could also decrease the serum FFA levels at 3h and 6h after LAD occlusion.

---37: Vopr Onkol. 1992;38(9):1073-80.

[The inhibiting effect of phytoadaptogenic preparations from bioginseng, Eleutherococcus senticosus and Rhaponticum carthamoides on the development of nervous system tumors in rats induced by N-nitrosoethylurea] 

Bespalov VG, Aleksandrov VA, Iaremenko KV.
The study was concerned with the inhibitory effect of officinal preparations of phytoadaptogenic drugs such as bioginseng and Eleutherococcus senticosus and Rhaponticum carthamoides root extracts on the carcinogenesis induced by transplacental administration of N-nitrosoethylurea. The phytodrugs were given orally over a year. The administration of the drugs was followed by longer survival of the rats and lower occurrence and/or multiplicity of tumors (mainly those of the central nervous system). The drugs were placed in the order of decreasing anticarcinogenic activity as follows: bioginseng, Rhaponticum carthamoides extract and Eleutherococcus senticosus extract.

---38: Mem Inst Oswaldo Cruz. 1991;86 Suppl 2:159-64.

Immunomodulating Chinese herbal medicines. 

Li XY. Shanghai Institute of Materia Medica , Chinese Academy of Sciences.

Traditional Chinese medicine always pays close attention to the strengthening of the patient’s general resistance against illness, there are many Chinese herbs used for thousands of years are considered as tonics. Animal experiments and modern clinical trails have shown that quite a number herbs are immunologically active, and most of the tonics are excellent immunomodulating agents, such as polysaccharides or saponins isolated from Astragalus mongholicus, Acanthopanax senticosus and Panax notoginseng, which stimulated macrophages, promoted antibody formation, activated complement and increased T lymphocyte proliferation . Moreover, some of them were proved to be anti-irradiative and protected animals from liver intoxications. On the other hand, some anti-inflammative or anti-pyretic herbs such as Tripterygium wilfordii, Aconitum and Artemisiae species were proved to have immunosuppressive principles, some of them were now used clinically for the treatment of rheumatoid arthritis, chronic nephritis, systemic lupus erythematosis and various skin disorders. Pharmacological studies revealed that they have depressant effect on most of the humoral-immunity but not on the cell-mediated immunity. Some of them stimulated adrenal cortex functions and prolonged the survival time of transplanted allograft tissues.

39: Int J Immunopharmacol. 1991;13(5):549-54.Immunomopharmacological effects of polysaccharides from Acanthopanax senticosus on experimental animals. Shen ML, Zhai SK, Chen HL. Department of Pathology, University of Illinois , Chicago.
Polysaccharides PES isolated from a common Oriental herb Acanthopanax senticosus were found to have awide spectrum of immunomodulatory activities on experimental animals. The potential usefulness of these polysaccharides is suggested in the observations that PES inhibited transplanted tumor growths and ameliorated toxicities of the toxic substances in experimental animals. Of most interest is the observations that they suppressed human TB propagation in mice and guinea pigs, as evaluated by lymph node responses and OT skin tests in the guinea pig model, and the quantitation of the TB in the lungs in the mouse model.39: Chem Pharm Bull ( Tokyo ). 1990 Jun;38(6):1763-5.Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. Nishibe S, Kinoshita H, Takeda H. Faculty of Pharmaceutical Sciences, Higashi Nippon Gakuen University, Hokkaido, Japan.Ten phenolic compounds, isofraxidin (1), (+)-syringaresinol-di-O-beta-D-glucoside (2), syringin (3), chlorogenic acid (4), isofraxidin-7-O-beta-D-glucoside (5), 2,6-dimethoxy-p-benzoquinone (6), (+)-pinoresinol-O-beta-D-glucoside (7), (7), (+)-syringaresinol-O-beta-D-glucoside (8), (+)-pinoresinol-di-O-beta-D-glucoside (9) and (+)-medioresinol-di-O-beta-D-glucoside (10), were isolated from the stem bark of Acanthopanax senticosus Harms and identified, respectively. The aqueous extract of the stem bark exhibited a prolonging effect on the exercise time to exhaustion in chronic swimming stressed rats. The effect on the exercise time in the chronic swimming stressed rats was respectively tested for compounds 2 and 4, which are major constituents of the stem bark. As a result, it was indicated that compound 2 is the compound responsible for part of the pharmacological effect which the aqueous extract of the stem bark showed.40: Zhong Xi Yi Jie He Za Zhi. 1990 Mar;10(3):155-6, 132.[Effect of a mixture of Acanthopanax senticosus and Elsholtzia splendens on serum-lipids in patients with hyperlipemia] 
Shi Z, Liu C, Li R. Institute of Space Medico-Engineering, Beijing .

The serum-lipids were determined in 31 hyperlipemia patients before and after treated with the mixture of Acanthopanax senticosus and Elscholtzia splendens. While the mean value of serum beta-lipoprotein decreased from 902 +/- 228 mg/dl to 608 +/- 189 mg/dl (P less than 0.001), the mean value of HDL-C increased from 52.6 +/- 12.5 mg/dl to 61.2 +/- 15.4 mg/dl (P less than 0.001). Thus the ratios of HDL-C to total cholesterol (HDL-C/TC) and to LDL-C (HDL-C/LDL-C) increased significantly, the arteriosclerosis index (AI) decreased significantly. The results indicate that the mixture of Acanthopanax senticosus and Elsholtzia splendens could improve the lipid-metabolism in hyperlipemia patients so that it might play a good role in preventing or alleviating arteriosclerosis .

41: Zhonghua Zhong Liu Za Zhi. 1989 Sep;11(5):338-40.

Immunoregulatory effect of polysaccharide of Acanthopanax senticosus (PAS). I. Immunological mechanism of PAS against cancer 

Xie SS. Beijing University of Medical Sciences.

The effect of PAS against cancer and its immunoregulatory function were studied. The results indicated that PAS was able to inhibit tumor growth and prolong the survival time of tumor-bearing mice significantly at the dose of 100 mg/kg/day, ip. In addition, PAS was also able to increase the response of murine spleen cells to Con A and LPS, the amount of IgM and IgG PFC in murine spleen and the DTH response induced by BSA. These results indicate that the inhibitory effect of PAS on tumor growth is related to the enhanced immune response.

42: Zhongguo Zhong Yao Za Zhi. 1989 Aug;14(8):493-5, 508, 512.

Effects of ciwujia (Acanthopanax senticosus Harms) on reperfusion-induced arrhythmia and action potential alterations in the isolated rat heart 

Tian BJ, Gao TL, Song ZL. 

By means of Langendorff method and standard microelectrode techniques the effects of Ciwujia on reperfusion induced arrhythmias and action potential alterations were studied in isolated rat heart with transient coronary occlusion. Inclusion of Ciwujia extract (equivalent to 1.2 and 2.4 mg crude drug/ml) was found helpful inreducing reperfusion induced ventricular fibrillation and ventricular tachycardia. Associated with this reduction in rhythm disturbances was an increase in the total duration of normal sinus rhythm during the 3 min reperfusion period. With the administration of Ciwujia the number of cells with abnormal action potential configurations was significantly reduced. This confirms that Ciwujia can protect myocardium from electrophysiological abnormalities, and therefore reduces the incidence of malignant arrhythmias.

Journal Cover43: Exp Hematol. 1988 Oct;16(9):801-6.Radioprotection of hemopoiesis conferred by Acanthopanax senticosus Harms (Shigoka) administered before or after irradiation. Miyanomae T, Frindel E. Unite de Recherches sur la Cinetique Cellulaire , INSERM U.250, Villejuif, France.
Acanthopanax senticosus Harms (Shigoka) extract has been observed to have radioprotective effects on hemopoiesis of irradiated mice (CBA/olac) when administered before or after irradiation by 60Co. The mechanisms of action were explored by studying the following parameters: 1) survival after lethal doses of irradiation; 2) recovery of spleen colony-forming units (CFU-S); 3) protective effect on endogenous CFU-S; and 4) effect on self-renewal of CFU-S. 1) The 30-day mortality due to bone marrow failure after irradiation was significantly reduced in Shigoka-treated mice. The maximum effect of the extract (80% survival) at a dose of 5 mg was observed when given intraperitoneally 24 h before a lethal dose of irradiation (9.5 Gy) and it was still effective when administered as late as 12 h after irradiation (30% survival). The radioprotective effect of Shigoka extract given before irradiation was not due to an increase in the total number of CFU-S but probably due to quiescent CFU-S that entered DNA synthesis (S-phase) 24 h after the injection of Shigoka extract. 2) Recovery of CFU-S in mice given the extract within 15 min after 4.75 Gy of whole body irradiation was also enhanced, especially in the spleen. The number of CFU-S in the bone marrow 24 h after irradiation showed a marked decrease. It returned to normal values in the bone marrow at day 11 in Shigoka-treated mice and at day 15 in nontreated irradiated mice. CFU-S in the spleen recovered more rapidly with an overshoot from days 7 to 21 in the Shigoka-treated mice, whereas in control irradiated mice it did not reach the normal value until day 21. 3) Nine days after sublethal doses of irradiation (7.0 Gy) the number of endogenous spleen colonies (endogenous CFU-S) was highest in mice given the extract 24 h before irradiation. The extract administered as late as 24 h after irradiation also resulted in an increase of the endogenous CFU-S. 4) The number of CFU-S in each 9-day endogenous CFU-S was 73.9 +/- 7.2 per nodule in treated mice and 0.2 +/- 0.1 per nodule in irradiated control mice, which suggests increased self-renewal of CFU-S in Shigoka-treated groups. These results suggest that the radioprotection conferred by Shigoka extract results from enhanced stimulation of CFU-S not only toward proliferation but also toward CFU-S self-renewal. These two phenomena could explain the protective effects of Shigoka extract administered even after irradiation. 
44: Am J Chin Med. 1981 Spring;9(1):48-56.Effect of Panax ginseng saponins and Eleutherococcus senticosus on survival of cultured mammalian cells after ionizing radiation. Ben-Hur E, Fulder S.
Panax ginseng saponin and Eleutherococcus senticosus extract were applied to cells in culture in order to assess the effect of these substances on resistance to gamma-irradiation. Eleutherococcus was slightly radio protective . However, ginseng saponin at a dose of 10 microgram/ml was significantly radioprotective (Do = 2.25 Gy) compared to control (Do = 1.80 Gy) when it was present prior to gamma-irradiation. It enhanced radiation response if it was also present for 4-6 hours after gamma-irradiation (Do = 1.10 Gy). Ginseng-treated cells made 30% less RNA and 14% more protein during a 1 hour pulse of labeled intermediates. The cells were morphologically altered. It is concluded that ginseng saponin can increase radiation resistance. The effect is indirect, due to alterations in cell physiology rather than DNA repair processes.
44: J Nat Prod. 1987 Nov-Dec;50(6):1059-64.Potential inhibitors of platelet aggregation from plant sources, III. Yun-Choi HS, Kim JH, Lee JR. Natural Products Research Institute, Seoul National University , Korea .
3,4-Dihydroxybenzoic acid (DBA) was isolated from Acanthopanax senticosus as an antiplatelet aggregatorysubstance. This paper also reports the results of the investigations on the structural activity relationships among the various dihydroxybenzoic acid derivatives against rat platelet aggregations induced by ADP (adenosine 5′-diphosphate), AA (arachidonic acid), or collagen.45: Farmakol Toksikol. 1986 Sep-Oct;49(5):73.Effect of the glycosides of Eleutherococcus senticosus on the hemodynamic indices of children with hypotensive states Kaloeva ZD. Efficacy of extractum eleutherococci fluidum in children aged 7-10 years with a stable stage of neurocirculatory hypotension was shown. A positive dynamics of subjective evidence, a statistically significant elevation of levels of systolic and diastolic pressures low before treatment and an increase of total peripheral resistance were noted. 46: Arzneimittelforschung. 1985;35(7):1069-75.[Immunostimulating action of polysaccharides (heteroglycans) from higher plants] 

Wagner H, Proksch A, Riess-Maurer I.

From the water or alcaline-water extracts of Echinacea purpurea (L.) Moench. and -angustifolia DC., Eupatorium cannabium L. and -perfoliatum L., Chamomilla recutita L. Rauscher, Calendula officinalis L., Baptisia tinctoria (L.) R. B., Achyrocline satureioides DC., Arnica montana L., Sabal serrulata Roem. et Schult., and Eleutherococcus (Acanthopanax) senticosus Maxim. polysaccharide fractions with molecular weights in the range of 25 000 to 500 000 and higher have been isolated, which, according to the granulocytes- and carbon clearance tests,showed significant immunostimulating activities . The isolated compounds belong to the group of watersoluble, acidic branched-chain heteroglycans. Their immunostimulating activity is compared and discussed with respect to other polysaccharides of biological activity.

47: Jpn J Pharmacol. 1984 Jun;35(2):79-85.

The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats. 

Martinez B, Staba EJ.

Relative and total amount of saponins in Panax ginseng, Panax quinquefolius, Aralia mandshurica and Eleutherococcus senticosus were determined by thin-layer chromatography and by a spectrophotometric method. The ginsenoside Rg1 was present in American ginseng. Aralia and Eleutherococcus did not contain diol- and triol-type ginsenosides. Low concentrations of ginsenosides were found in Oriental red ginsengs (1.4-2.7%). Orally administered Araliaceae saponin extracts did not affect plasma lactic acid, glucagon, insulin or liver glycogen levels in exercised rats and did not prolong their swimming time. Plasma glucose levels in resting rats were decreased by saponin extracts of Canadian white, American red, Sanchi, Aralia,Eleutherococcus , Korean red and Shiu-Chi ginsengs.

48: J Ethnopharmacol. 1984 Apr;10(2):235-41.Effects of Eleutherococcus senticosus extracts on hexobarbital metabolism in vivo and in vitro. Medon PJ, Ferguson PW, Watson CF.
Eleutherococcus senticosus (Siberian Ginseng) is widely exported from China as a health food. Pharmacologically it has been classified as an adaptogen and enzyme induction has been proposed as its mechanism of action. To evaluate this hypothesis E. senticosus was administered to mice on an acute (40-320 mg/kg i.p., X 1 day) or chronic (80-320 mg/kg i.p., X 4-5 days) basis. Sleep latency and duration, in response to hexobarbital sodium (100 mg/kg i.p.), were determined either 1 h (acute and chronic) or 24 h (chronic) following the last E. senticosus injection. E. senticosus produced a sedative effect which decreased the sleep latency (47%) and increased sleep duration (45-228%) following acute administration. A similar effect was seen following chronic administration (125-202% increase in sleep duration). E. senticosus was also shown to produce an inhibition (66%) of hexobarbital metabolism , in vitro, as compared to controls. These data support enzyme inhibition rather than enzyme induction as a mechanism for the actions of Siberian Ginseng.
49: J Pharm Sci. 1984 Feb;73(2):270-2.Cytotoxic effects of Eleutherococcus senticosus aqueous extracts in combination with N6-(delta 2-isopentenyl)-adenosine and 1-beta-D-arabinofuranosylcytosine against L1210 leukemia cells. Hacker B, Medon PJ.
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 .50: Arzneimittelforschung. 1984;34(6):659-61.[Immunostimulant action of polysaccharides (heteroglycans) from higher plants. Preliminary communication] Wagner H, Proksch A, Riess-Maurer I.From the water or alcaline-water extracts of Echinacea purpurea (L.) Moench and -angustifolia DC., Eupatorium cannabinum L. and -perfoliatum L., Chamomilla recutita (L.) (Rauscher), Calendula officinalis L., Baptisia tinctoria (L.) R.B., Achyrocline satureoides DC., Arnica montana L., Sabal serrulata Roem et Schult. andEleutherococcus senticosus Maxim. polysaccharide fractions with molecular weights in the range of 25 000 to 500 000 and higher have been isolated, which, according to the granulocytes- and carbon clearance tests, showed significant immunostimulating activities. The isolated compounds belong to the group of water-soluble, acidic heteroglycanes. The linkages in the different polysaccharides do not represent a uniform structure type.51: Endocrinol Jpn. 1982 Oct;29(5):567-73.Panax ginseng and Eleuthrococcus senticosus extracts–in vitro studies on binding to steroid receptors. 

Pearce PT, Zois I, Wynne KN, Funder JW. 

We have examined the binding of 44% saponin from Panax ginseng, and extracts from Eluthrococcus senticosus (Siberian ginseng) to classical steroid receptors in vitro. Both extracts had demonstrable affinity for progestin, mineralocorticoid and glucocorticoid receptors; the Siberian ginseng also bound to estrogen receptors.Highest affinity binding was to glucocorticoid receptors, with an approximate Ki of 8 x 10(-6) M for Panax ginseng. Such interactions may explain the reported glucocorticoid-like effects of ginseng in vivo.

52: Di Yi Jun Yi Da Xue Xue Bao. 2003 Apr;23(4):355-7.
High-performance liquid chromatography combined with mass spectrum analysis for identifying the antifatigue components in Acanthopanax senticosus Harms. 

Wang ZC, Qiao SY, Ma AD. Central Laboratory, First Military Medical University , Guangzhou 510515, China .

The roots of Acanthopanax senticosus (Rupr. et Maxim.) Harm were obtained for the acquisition of the crude extractives to isolate the 19 components by means of preliminary extraction and isolation. High-performance liquid chromatography followed by primary and secondary mass spectrum analysis (HPLC/MS/MS) was employed to identify the antifatigue components from the extracts of the plant with reference to the literature. Good isolation results were achieved and several known and unknown chemical compounds were identified, for instance, in one sample (No. 11) 5 known components were detected along with 6 unknown compounds with relative molecular mass of 302, 318, 346, 354, 390, and 406, respectively.

53: Se Pu. 2002 Nov;20(6):543-5.

[Separation of eleutheroside E from crude extract of Radix Acanthopanacis Senticosus by analytical and preparative high-speed countercurrent chromatography] 

Wei Y, Zhang TY, Wu KY. Beijing Research Center for Separation & Purification Technology of Natural Products, Beijing Institute of New Technology Application, Beijing 100035, China.
Analytical high-speed countercurrent chromatography (HSCCC) was used for the systematic optimization of the two-phase solvent system to separate eleutheroside E from crude extract of Radix Acanthopanacis Senticosus. Eleutheroside E was obtained by preparative HSCCC with two-phase solvent system composed of chloroform-methanol-isopropanol-water (5:6:1:4 in volume ratio). The mobile phase is the lower phase and operated at a flow-rate of 2.0 mL/min, while the apparatus rotated at 800 r/min. High performance liquid chromatographic analysis of eleutheroside E revealed that its purity was over 98%. HSCCC is a useful method for the separation of natural products.

54: Phytochem Anal. 2002 Nov-Dec;13(6):316-28.

Identification of isomeric dicaffeoylquinic acids from Eleutherococcus senticosus using HPLC-ESI/TOF/MS and 1H-NMR methods. 

Tolonen A, Joutsamo T, Mattlla S. Department of Chemistry, University of Oulu, PO Box 3000, 90014 Oulu, Finland.

Liquid chromatography-electrospray time-of-flight mass spectrometry (HPLC-ESI/TOF/MS) and a novel NMR technique, developed to maximise the sensitivity obtained from the standard NMR spectrometer, have been applied to the identification of the phenolic constituents of Eleutherococcus senticosus. In addition, molecular modelling and dihedral bond angle calculations based on the vicinal 3JHH-coupling constants have been used in the unambiguous assignment of signals in the 1H-NMR spectra. 5′-O-Caffeoylquinic acid and three isomeric compounds, 1′,5′-O-dicaffeoylquinic acid, 3′,5′-O-dicaffeoylquinic acid and 4′,5′-O-dicaffeoylquinic acid, have been isolated and identified from a sample. The isolation and structure determination of the latter two compounds are reported for the first time from this plant.

Cover Image55: Rapid Commun Mass Spectrom. 2002;16(4):264-71.Analysis of flavonoid constituents from leaves of Acanthopanax senticosus harms by electrospray tandem mass spectrometry. Chen M, Song F, Guo M. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun , People’s Republic of China .
Three known flavonoids, quercetin, quercitrin (quercetin-3-0-rhamnoside) and rutin (quercetin-3-0 rutinoside), have been identified for the first time in the leaves of Acanthopanax senticosus Harms by using electrospray tandem mass spectrometry techniques (ESI-MS(n)). The flavonoid hyperin (quercetin-3-0-beta-galactoside), already known to be present, was also investigated. The diagnostic fragment ions of the aglycone quercetin were obtained in the ESI-MS(n) experiments, and a fragmentation mechanism proposed.
56: Planta Med. 2001 Nov;67(8):776-8.A new lignan glycoside from Eleutherococcus senticosus. Li XC, Barnes DL, Khan IA. National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy , University of Mississippi , Mississippi 38677 , USA .

A new lignan glycoside, named eleutheroside E(2) (1), has been isolated from the roots of Eleutherococcus senticosus (known as “Siberian ginseng”), along with isomaltol 3-O-alpha-D-glucopyranoside (2), eleutherosides B, E and E(1), and thymidine. The structure of 1 was established by spectral interpretations as episyringaresinol 4″-O-beta-D-glucopyranoside. Compound 2 is described here for the first time as a naturally occurring compound.

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