The Adaptogen Concept in the Modern Age
Since the publication of Il Brekhman’s landmark articles in 1969, adaptogen research has proceeded. Brekhman himself continued studying the adaptogens he had previously identified. Independent researchers have also investigated Brekhman’s adaptogens. Indeed, drugs like Eleutherococcus senticosus, Panax ginseng, Rhodiola rosea, and Schizandra chinensis have been scrutinised by researchers around the world. In addition, researchers have used Brekhman’s criterion to identify additional adaptogens; botanical drugs like Withania somnifera have surfaced through these efforts. To develop an appreciation for the adaptogen concept, and Brekhman’s adaptogen criterion, this chapter applies his criterion to five well?researched drugs: Eleutherococcus senticosus, Panax ginseng, Rhodiola rosea, Schizandra sinensis, and Withania somnifera. Although his research focused on Eleutherococcus senticosus and Panax ginseng, of the aforementioned tonic drugs, the first four botanical drugs were identified by Brekhman as adaptogens. Brekhman did not study Withania somnifera is an adaptogen, but it is revealed to be one by applying his criterion.
Significant phytochemicals include eleutheroside A?M, glycans (eleutherans), polysacharidespes?
a, polysacharides?pes?b, resin, saponins, and senticoside E?F. (4)
History Eleutherococcus senticosus (ES) is a thorny shrub found growing in Far Eastern Russia, Northeastern China, Korea, and Japan. Though the dominant species in this range is ES, there are 15 known species growing between the Himalayas and Japan. The drug is used as a tonic throughout Asia. For example, the Japanese use it to boost general vitality. The drug came to the attention of the rest of the world through Russian work with and use of the drug. Porphyrri Kirilov, while acting as the physician at the Russian Ecclesiastical mission to Peking (1830–1841), noticed ES. A plant collector as well as a medical man, Kirilov was impressed with the drug and brought samples back to central Russia when his post in China concluded. The drug lingered in medical circles in Russia until the middle of the 20th century. (5) In the 1950’s II Brekhman screened the Araliaceae family of plants for adaptogens and identified ES as an adaptogen. Brekhman, who worked in Siberia, focused much of his early studies on it. Thus ES became known as “Siberian ginseng.” Brekhman’s findings were compelling enough to intrigue other researchers and, over time, it has become a well?researched adaptogen.
The Adaptogen criterion: Brekhman’s research. Brekhman observed ES was very low in toxicity. His research revealed that doses of ES, large enough to increase non?specific resistance, did not cause significant disorders in normal function of the organism. (1–2) ES, then, satisfied his first criteria of an adaptogen. To fit his second criteria, ES had to increase resistance to a variety of physical, chemical, and biological stressors. In Brekhman’s terms, the adaptogen had to offer universal defence. To test ES, he conducted the following experiments.
Stress Using his animal model to test the effects of ES, Brekhman noted that following exposure to stress, the organs of the animals treated with the crude drug and isolated saponins did not show the usual signs of stress seen in the control animals. The drugs inhibited a major change in the weight of the adrenals, thymus, spleen, and thyroid demonstrated in the control animals. As well, shifts in blood chemistry and metabolism were distinctly modified. In other words, the pathological changes usually associated with stress did not occur. (1?2)Some saponins isolated from ES had a stronger anti?stress effect than others. Eleutheroside E had the strongest action, Eleutheroside B1 had a weak anti?alarm activity, and Eleutheroside C had no anti?alarm action at all. (1–2)
Fatigue Brekhman looked to see if ES and its saponins prolonged the time to physical collapse in the animal model. The question was would the drug increase resistance to fatigue? Rats treated with ES, in comparison to controls, were able to swim 52 minutes longer, an increase in swimming time of 9.2%. Moreover, they did not manifest the usual pathological consequences of stress (adrenal exhaustion, gastric ulceration, thymico?involution, etc.). In other tests, Brekhman foundthat time to complete exhaustion, when the test animal would drop to the electrified floor, was increased with the use of ES and its isolated saponins. Again, Brekhman found that some ES saponins had a stronger anti?fatigue effect than other saponins. (1–2)
Radiation ES was also found to have a radio?protective action in single x?ray irradiation. In prolonged irradiation, ES doubled the lifetime of rats and improved the state of their blood and other indices. Brekhman’s research revealed that ES, used in combination with antibiotics, increased the life span of irradiated animals three fold. (1–2)
Alloxan induced diabetes ES reduced weight loss, reduced urine blood sugar levels, and prolonged life span of rats with alloxan induced diabetes. (1–2)
ES reduced chemically induced tumours, inhibited urethane induced adenoma, 6? methylthiouracil induced thyroid tumours, and indole induced myeloid leukaemia. ES also reduced spontaneous tumours, especially spontaneous mammary gland tumours and spontaneous leukaemia. In addition, ES caused a reduction of transplants of Ehrlich, lymphosarcoma, and other transplanted tumours. It also caused a substantial inhibition of metastasis. Lastly, ES showed a radio protective and anti?toxic action towards anticancer drugs and radiotherapy. (1–2)
Narcotics ES was determined to have an anti?narcotic action in Brekhman’s studies. It showed activation on the EEG and diminished the depressed states caused by chloral hydrate, medinal, and aminasin. It also inhibited the activity of the drugs on the inner cortex. (1–2)
Hypertension In acute hypertension, a mild hypotensive activity was noted for ES. (1–2)
Anabolic activity ES exhibited three actions that indicated anabolic activity; it increased body weight, sped albumen replacement after a massive bleed, and increased immune cell production. However, unlike anabolic steroids which had an across the board effect, this anabolic activity wasmanifested only when it was required. In addition, ES had no virilizing effect. (1–2)
Physical and mental strain In Brekhman’s studies ES was found to alter anatomic and biochemical manifestations of the Alarm Reaction phase of the GAS including a reduction of activation of the adrenal cortices,thymicolymphatic involution, and bleeding ulceration of the stomach. Under physical strain, ES contributed to a sparing use of carbohydrates and enhanced glycogen and high?energy phosphorus compound use. (1–2)Efficiency is an integral and very sensitive index of the general state of the organism. His research showed that ES caused an increase of physical and mental efficiency after a single dose(stimulant) or a prolonged dosing (tonic). Stimulant doses differed from Benzedrine like compounds in that ES was devoid of pronounced excitant action and did not alter the ability of the organism to fall asleep or stay asleep. The saponins of ES were determined to be more active at increasing physical and mental efficiency than the crude drug. (1–2)
Normalising effect of ES To fit his third criteria, ES had to possess normalising action irrespective of the direction of the pathological changes. Brekhman observed ES had this capability. Specifically, ES was found to impede hypertrophy (ACTH induced) and atrophy (Cortisone induced) of the adrenal glands. (1– 2) It also impeded hypertrophy (thyreoidin induced) and atrophy (6?methylthiouracil induced) of the thyroid gland. (1–2) Further, ES reduced sugar levels in alimentary (glucose) and adrenal hyperglycaemia and it decreased hypoglycaemia induced by insulin. (1–2) In addition, ES normalised leukocytosis induced by the parenteral administration of milk and neutropenia induced by the endotoxin of dysenteric microbe. Lastly, ES normalised erythrocytosis caused by cobaltous nitrate and erythropenia caused by phenylhydrazine. (1–2)
ES at the cellular level Brekhman presented data that adaptogens worked on a cellular level, specifically acting as antioxidants and affecting the biosynthesis of protein and nucleic acid. (1–2) His researched revealed that ES exerted a protective action in the case of irradiation of diploid yeast. It also had a marked
protective effect when erythrocytes were subject to artificial radiomimetic substances (i.e. oxidised oleic acid). Substances in ES possessed the same anti?radical and anti?oxidant activity. Prophylactic and medicinal effects were obtained in pathological states (stress, irradiation, cancer) in which free radical caused disturbance played a role. Brekhman noted that ES did more than protect cells from damage. ES also had the capacity to switch cells on. The anabolic action of ES is an example of this ability; the stimulation of immunecell production and activity indicated the processes of biosynthesis of protein and nucleic acid.
Additional findings While Brekhman was working, a peculiar fact came to the surface. Namely, the effect of ES only became apparent when the resistance of the organism diminished or the organism was taxed with extra demands. In a normal organism or an organism not experiencing over taxation, ES had
no effect. (1–2) Contemporary studies involving normal unstressed individuals have also
demonstrated that ES does not cause physiological variations in unstressed populations. (20, 21)
Organisms have an in built ability to resist destructive forces, be they chemical, biological, or
physical. The Alarm Reaction phase of the GAS, largely mediated by the adrenal glands, is a
physical manifestation of this inherent resistive force. Brekhman concluded that the “State of
Non?specifically Increased Resistance,” or SNIR, caused by ES was more than the general
adaptation reaction. The SNIR, in contrast to the AR, was always beneficial to the organism,
might last comparatively long, and was not accompanied by the usual pathological changes seen
in the AR. Indeed, Brekhman demonstrated that ES created a superior State of Resistance to that which an organism would have naturally.
The Adaptogen criterion 1960–1980 Norman Farnsworth and a team of researchers at the Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois, undertook a comprehensive survey of Eleutherococcus senticosus literature between 1960 and 1980. The result was the paper entitled “Siberian Ginseng: Current Status as an Adaptogen.” (3) The paper examined 220 ES studies and summarised the work found therein. Most of the studies were done in foreign
language. The findings that follow, presented by Farnsworth and his team, support Brekhman’s
conclusions about ES. ES conformed to the first adaptogen criteria in numerous studies where it was observed that there is virtually no lethal dose of ES. Even at high doses, no teratogenic effects were described in a variety of pregnant animals. Moreover, in studies involving 6000 humans, no toxicity was reported. (3)
Animal Studies A collection of studies revealed that ES displayed an anti?toxic effect, acted as an anti?narcotic, displayed an anti?infection effect via immune stimulation, increased tolerance to hypothermia, increased work capacity, reduced radiation damage, decreased physiological damage caused by stress, helped the body respond to massive bleeds, and improved adrenal function thereby countering fatigue. (3) In other words, ES displayed the second criteria of an adaptogen, namely
it increased resistance to a wide range of stressors. Animal research demonstrated that many of these effects are also found in ES saponins. For example, Eleutherosides A, C, D, E, and F increased the time to complete exhaustion in exhaustion models. Eleutheroside B showed an anti?stress effect and Eleutheroside B1 showed an anti?alarm effect. Polysaccharides PES?A and PES?B heightened immune response. (3)Eighteen animal studies demonstrated that ES played a role in cancer by reducing tumour take and metastasis in chemically induced and spontaneous tumours. (3) The “citrovorum factor” is used to decrease the toxicity of methotrexate in cancer therapies and there is evidence that ES has a similar effect. Furthermore, ES reduced the toxicity and increased anti?tumour effects of
rubromicin C, Thio?tepa, Dopan, 6?mercaptopurine, cyclophosphan, ethymidine, benzo?TEPA,
and sarcolysin. (3)
ES was found to normalise a collection of physiological abnormalities and thus fit the third
criteria of an adaptogen. Numerous studies demonstrated it normalised blood sugar levels,
reduced liver and adrenal cholesterol synthesis, lessened brain ischemia, countered CNS
depression, increased conditioned response to stimuli, countered endocrine depression/activation
of the endocrine system, countered adrenal failure/reduced inflammation in adrenalectomized
animals, and countered liver disease/induced liver cell regeneration.
In addition, researchers demonstrated that certain active constituents of ES also have a normalising effect. Eleutheroside B showed an androgenic effect, increasing RNA content of
seminal vesicles and prostate of treated animals. Eleutheroside B1 also increased RNA in seminal vesicles and prostate of treated animals. Isofraxidin displayed choleretic effect. (3)
Human studies ES was administered to over 2100 human subjects having no pathologies in 44 studies. In these studies, it was determined to increase human’s ability to withstand stressors such as heat, noise, motion, work load increase, exercise, and decompression. It was found to improve auditory
disturbances, mental acuity, work output, and quality of work under stressed conditions. ES increased athletic performance by raising resistance to fatigue. In one study of 1000 factory workers living in the polar region and taking ES, there was a 40% reduction in lost days and sick days were reduced by 50%. (3) In other words, ES raised resistance in general. 200 male and female subjects, ranging from 19 to 60 years of age, with various aliments were given ES. Across a wide range of pathology (atherosclerosis, hypo?tension, hyperglycaemia, rheumatic heart disease, neurasthenia, etc.), ES was shown to correct pathological process and display a normalising effect, regardless of the direction of pathological changes. (3) Once again, ES demonstrated adaptogenic capacity as defined by Brekhman’s criterion.
Adaptogen criterion: 1980–2003 After 1980, ES research began to take place outside of Russia and Asia. It would appear that there was enough evidence coming out of Russia and various Asian countries to intrigue western researchers. This third wave of research also has resulted in ongoing validation of Brekhman’s earlier findings. Namely: • In various studies investigating ES, no side effects have been reported. (4–21) • ES increases immuno?globulin levels in mice before and during illness. (6) • ES exhibits an anti?fatigue, anti?stress, and immunity enhancing effect. (9) • ES acts as an immune modulator in activated whole blood cultures of ten healthy volunteers. (12) • ES increased interleukin 1 and interleukin 6 production in vitro using mononuclear phagocytes extracted from rat bone marrow. (13) • ES increased in vitro phagocytosis of Candida albicans by granulocytes and monocytes of healthy human donors by 45% (15)
• Polysaccharide fractions extracted from ES with molecular weights of between 25,000
and 500,000 showed significant immunity stimulating activities according to
granulocytes and carbon clearance tests. (19)• In a human study, ES drastically increased the absolute number of immune competent cells, with an especially pronounced increase in T lymphocytes, primarily of the helper/inducer type. There was also an increase in cytotoxic and natural killer
cells and an enhancement of the Activation State of lymphocytes. (17)
• ES inhibited RNA viruses. The productive replication of human rhinovirus (HRV), respiratory synctial virus (RSV), and influenza A virus in cell cultures infected with these viruses was inhibited. (10) • ES inhibits catechol?O?methyl transferase that degrades stress hormones. The implication being that ES acts as an anti?stress drug, in part, by maintaining stress hormone levels. Researchers conclude that the increase in energy experienced when ES is administered may be due to enhancement of stress hormones. This in turn causes liberation of energy reserves. (11)• In a study looking at physical fitness in 50 healthy human subjects, ES demonstrated a positive effect in cellular defence, physical fitness, and lipid metabolism. (14)• The administration of ES in conjunction with transplacental administration of Nnitrosoethylurea resulted in a longer survival time of rats and a lower occurrence and
or multiplicity of tumours (mainly nervous system). (16)
• ES inhibited mast cell mediated anaphylaxis in vivo and in vitro murine model. (7)
• ES exhibited activity on the Central Nervous System and had an antidepressant
• ES was found to remarkably reduce blood sugar levels in normal and alloxan induced diabetic mice. (18)
Conclusion Clearly, Eleutherococcus senticosus fulfils Brekhman’s adaptogen criterion. Subsequent researchers have demonstrated that this is the case. Indeed, there is substantial evidence to support its use in raising resistance to stressors. In addition, it may be useful in two specific instances.
ES and viral disease Numerous studies dating from 1960 to present indicate ES may have a role in raising resistance to viral infection. The drug has been shown to increase immune cell counts (17), increase immune cell production of immune products (immuno?globulin, interleukin, etc.) (12), and to directly inhibit viral replication (RNA viruses) (10). Lastly, viral disease represents a chronic stressor
agent and ES has been shown to raise resistance to chronic stress. (1–21)
ES and cancer ES may have a role in cancer resistance and treatment. The immune system is the first line of defence against Carcinogenesis and ES has been shown to increase immune function. (1–2) In
addition, ES has been shown to raise resistance to radiation and toxic chemicals (1–2), both of
which factor into cancer therapies.
References for Eleutherococcus senticosus
1. Brekhman, II. and Dardymov, IV. Pharmacological Investigation of Glycosides from
Ginseng and Eleutherococcus. II. Lloydia, March 1969, Volume 32, Number 1. P. 46–51.
2. Brekhman, II and Dardymov, IV. New Substances of Plant Origin Which Increase Nonspecific Resistance. Annual Review of Pharmacology. Henry Elliott, Editor. Annual Reviews, Inc. 1969. P. 419–430.
3. Farnsworth N, Kinghorn A, Soejarto D, and Waller D. Siberian Ginseng (Eleutherococcus
senticosus): Current Status as an Adaptogen. Economical and Medicinal Plant Research,
volume 1, 1985. P. 155–215.4. Duke, James. Handbook of Phytochemical constituents of GRAS drugs. CRC press. 1992. P. 240. 5. Davydov, M and Krikorian, A. Eleutherococcus senticosus as an adaptogen: a closer look. Journal of Ethnopharmacology 72(2000): 345–393.
6. Droned J et al. Estimation of humoral activity of Eleutherococcus senticosus. Acta Poll
Farm 2002 Sep–Oct; 59(5): 395–401. From PubMed abstracts. 7. Yi, JM ET al. Effect of Acanthopanax senticosus stem on mast cell dependent anaphylaxis. Journal of Ethnopharmacology 2002 Mar; 79(3): 347–52. From PubMed abstracts.8. Gaffney BT et al. The effects of Eleutherococcus senticosus and Panax ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes. Life Science 2001 Dec 14; 70(4): 431–42. From PubMed abstracts.9. Deyama T et al. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin 2001 Dec; 22(12): 1057–70. From PubMed abstracts. 10. Glatthaar?Saalmutter B et al. Antiviral activity of an extract derived from the roots ofEleutherococcus senticosus. Antiviral Research 2001 June; 50(3): 223–8. From PubMed abstracts.11. Gaffney BT et al. Panax ginseng and Eleutherococcus senticosus may exaggerate an already existing biphasic response to stress via inhibition of enzymes with limit the binding of stress hormones to their receptors. Medical Hypotheses 2001 May; 56(5): 567– 72. From PubMed abstracts.12. Scholmz MW et al. 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 senticosusroot. Phytotherapy Research 2001 May; 15(3): 268–70. From PubMed abstracts. 13. Steinmann GG. Immunopharmacological in vitro effects of Eleutherococcus senticosus extracts. Arzneimittelforschung 2001 Jan; 5(1):76–83. From PubMed abstracts.14. Szolomicki, J et al. The influence of active components of Eleutherococcus senticosus on cellular defence and physical fitness in man. Physiotherapy Research 2000 Feb; 14(1): 30–5. From PubMed abstracts. 15. Wildfeuer, A et al. The effect of plant preparations on cellular functions in body defence. Arzneimittelforschung 1994 Mar; 44(3): 361–6. From PubMed abstracts. 16. Bespalov VG et al. The inhibiting effect of phytoadaptogenic preparations from bioginseng, Eleutherococcus senticosus, and Raponticum carthamoides on thedevelopment of central nervous system tumours in rats induced by N?nitrosoethylurea. Vopr Onkol 1992; 38(9):1073–80. From PubMed abstracts. 17. Bohn B et al. Flow cytometric studies with Eleutherococcus senticosus as an immunomodulatory agent. Arzneimittelforschung 1987 Oct; 37(10): 1193–6. From PubMed abstracts. 18. Hikino H et al. Isolation and hypoglycaemic activity of eleutherans A?G: glycans of Eleutherococcus senticosus. Journal of Natural Products 1986 Mar–Apr; 49(2): 293–7. 19. Wagner H et al. Immunostimulating action of polysaccharides (heteroglycans) from higher plants. Arzneimittelforschung 1985; 35(7): 1069–75. From PubMed abstracts.20. Eschbach LF et al. The effect of Siberian ginseng (Eleutherococcus senticosus) onsubstrate utilisation and performance. International Journal of Sport Nutrition Exercise and Metablism 2000 Dec; 10(4):444–51. From PubMed abstracts.21. Dowling, EA et al. Effect of Eleutherococcus senticosus on submaximal and maximal exercise performance. Med Sci Sports Exerc 1996 April; 28(4): 482–9. From PubMed
Chinese Ginseng Araliaceae
Chemical constituentsSignificant phytochemicals include ginsenoside, ginsenoside F1?3, ginsenoside M?7?CD,ginsenoside RA?2, ginsenoside RB 1?3, ginsenoside RC, ginsenoside RD, ginsenoside RE,
ginsenoside RF, ginsenoside RG 1?2, ginsenoside RH1, ginsenoside RO, 2?glucoginsenoside RF,panacene, panasenoside, panaxic acid, panaxin, panaxydol, and panaxynol. (4)
History Panax ginseng (PG) has been used for centuries in Asia to stimulate the return of health and vitality amongst the ill and the elderly. Deemed one of the most powerful tonics known, traditional uses include treating massive blood loss in child delivery, tuberculosis, and age related physical and mental senility. Indigenous to China, Korea, and Japan, PG was a precious commodity and its collection and trade was a highly organised affair. The high regard in which Asians held PG quickly caught the attention of western communities in Asia. Once westerners experienced the drug, they too developed a taste for it, which added demand for, and increased the cost of, the drug. By the time Brekhman began working with adaptogens, PG?s reputation as a health building drug had spread around the globe. Though well known, widely sought after and extraordinarily expensive, little was known about the nature of the PG. It was only when Brekhman took an interest in PG that it shifted from mythical medicine to researched drug. Today, PG is one of the most thoroughly studied botanical drugs. A search of Pub Med, the online database of 4500 biomedical journals created by the American National Library of Medicine, reveals that 1434 Panax ginseng studies have been published between 1963 and 2003.
Indeed, the rate of research is increasing. Between 1963 and 1980, 172 studies are cited in Pub Med; between 1980 and 1990, 369 studies are cited; between 1990 and 2003, 892 studies are cited.
The adaptogen criterion: Brekhman’s research Brekhman’s research demonstrated that PG shows properties consistent with the adaptogen definition. He determined that PG had a low toxicity and did not pervert function. Research revealed that doses of PG, large enough to increase non?specific resistance, did not cause's significant disorders in normal function of the organism. (1–2) In other words, PG fit Brekhman’s first criteria of an adaptogen.
StressAgain, Brekhman employed the animal model to test the crude drug and its saponins’ capability to increase resistance in a non?specific way. His studies revealed that the organs of the animals
treated with both the crude drug and its isolated saponins did not show the usual signs of stress
that were seen in the control group. Like ES, Panax Ginseng inhibited a major change in the
weight of the adrenals, thymus, spleen, and thyroid, demonstrated in the control animals. As
well, shifts in blood chemistry and metabolism were also distinctly modified. Like ES, PG altered the anatomic and biochemical manifestations of the alarm stage of stress in Brekhman’s studies. He noted that when PG and various PG glycosides and their genins were used there was a reduction in adrenal activity, thymicolymphatic involution, and bleeding ulceration of the stomach. Some saponins isolated from PG had a stronger anti?stress effect than other saponins. Brekhman concluded that when PG or its glycosides were administered, the pathological changes usually associated with stress did not occur. (1–2)
Fatigue Again, applying his animal model, Brekhman’s tests revealed that the time to complete exhaustion could be delayed with the use of PG and its isolated saponins. (1–2)
Radiation Panax ginseng was found to have a radio protective action in single x?ray irradiation. In prolonged irradiation it doubled lifetime of rats and improved the state of their blood and other indices. (1–2)
Alloxan Induced DiabetesPG increased resistance to alloxan induced diabetes. (1–2)
Narcotic intoxicationPG inhibited narcotics action on the inner cortex of the brain. (1–2)
HypertensionIn acute hypertension, a mild hypotensive activity was noted for PG. (1–2)
Catabolism PG, like ES, exhibited three actions indicating anabolic activity; it increased weight, sped albumen replacement after a massive bleed, and increased immune cell production. Similar to ES, this anabolic activity was manifested only when it was required and PG had no virilizing effect.(1–2)
Physical and mental strain PG contributed to a sparing use of carbohydrates and to enhanced use of glycogen and highenergy phosphorus compounds, especially when the organism was under physical strain. Brekhman’s research showed that Panax ginseng also caused an increase of physical and mental efficiency after a single dose (stimulant) and prolonged dosing (tonic). The stimulant doses were low in toxicity, devoid of pronounced excitant action, and did not alter the ability of the organism to fall asleep or stay sleep unlike Benzedrine compounds. (1–2)
Normalising effect of PG Brekhman’s research probed PG further to determine if it had the capacity to normalise functions regardless of the pathological changes. He found PG impeded hypertrophy (ACTH induced) and atrophy (Cortisone induced) of the adrenal glands. (1–2) It impeded hypertrophy (thyreoidin induced) and atrophy (6?methylthiouracil induced) of the thyroid gland. (1–2) PG reduced sugar levels in alimentary (glucose) and adrenal hyperglycaemia and decreased hypoglycaemia induced by insulin. (1–2) PG also normalised leukocytosis induced by the parenteral
administration of milk and neutropenia induced by the endotoxin of dysenteric microbe. (1–2) Finally, PG normalised erythrocytosis caused by cobaltous nitrate and erythropenia caused by phenylhydrazine. (1–2)
PG at the cellular level Brekhman also presented data suggesting PG, like ES, worked on a cellular level. Similar to ES, PG revealed a marked protective effect when erythrocytes were subject to artificial radiomimetic substances i.e. oxidised oleic acid. Active substances in PG possessed anti?radical and antioxidant activity; prophylactic and medicinal effect were obtained in pathological states (stress, irradiation, cancer) in which free radical caused disturbance played a role. The anabolic action of PG, particularly the stimulation of immune bodies, suggests that stimulation of the biosynthesis of protein and nucleic acid play a significant role in its action. (2)
Additional findingsLike ES, Brekhman found the adaptogenic effect of PG only became apparent when the resistance of the organism diminished or the organism was taxed with extra demands. In a normal organism or an organism not experiencing over taxation, PG had no effect. (1–2) Numerous studies using healthy individuals substantiated this finding. (26, 27)Brekhman went on to demonstrate that in addition to reducing the damage associated with the Alarm Reaction phase, PG increased resistance to stressors. Again, Brekhman’s analysis of the data led him to conclude that a “State of non?specifically Increased Resistance” or SNIR caused by PG was more than the general adaptive reaction. Like ES, PG also created a super State of Resistance to that which an organism would have naturally.
Adaptogen criterion: 1969–1990 This time period was an active one in PG research. Pub Med lists 541studies published between these years. In 1991, Hiroshi Hikino published a paper entitled “Traditional Remedies and Modern Assessment: The Case of Ginseng.” The paper appeared in the CRC press book entitled “The Medicinal Plant Industry” and represents a summary of the research done between 1980 and 1990. The paper cites 163 studies, many in foreign language, and can be seen as the most comprehensive review of PG literature. The data presented by Hikino, which confirmed Brekhman’s findings, is as follows:• Research confirms that PG is non?toxic. The safety of ginseng has been demonstrated inmice, rats, rabbits, beagle dogs, and minipigs in short, medium and long term studies. (3)• Chronic PG supplementation provides significant protection against electroshock stress, heat stress, and fatigue stress in mice. (3)• PG increases resistance to radiation, carbon tetrachloride and thioacetamide exposure, and alcohol intoxication in animal studies. (3)• PG increases resistance to ageing. Ageing is associated with the death of certain cells that result in the loss of vitality and greatly contribute to senility. Ginsenosides were found to increase the life span of long lived proteins in the human body. Experiments have shown that it inhibited the intracellular protein degradation in confluent cultures of IMR?90 human diploid fibroblasts, inhibited proteolysis of long lived proteins selectively, and stimulated protein synthesis in human fibroblast. (3)• PG increases resistance to microbial infection in animals. Polysaccharides found in PG have been demonstrated to stimulate immune function and thereby offer increased immunity against microbial infection. In mice, they were found to stimulate phagocytosis, increase the production of antibodies, cause an increase of serum complement content, raise the serum IgG level, and increase the B lymphocyte to T lymphocyte cell ratio. (3) • PG increases resistance to cancer. It has been found to inhibit the spread of tumours, to inhibit the production of tumours caused by toxins, to increase tolerance to toxic antitumour drugs, and to stimulate Natural Killer cell activity which carries an intrinsic antitumour activity. In addition, PG has been found to stimulate reverse transformation in certain cancer cells. (3) • PG improves tissue wasting and may do so by stimulating protein synthesis. Experiments showed that ginseng fractions accelerated incorporation of orotic acid into liver nuclear RNA and into cytoplasmic RNA in rats. The implication being that PG accelerated nuclear replication. In addition it has been shown to activate every step of the biosynthesis of protein. Looking at bone marrow, research has shown that PG increases protein in blood serum and the liver. (3)• Studies reveal PG participates in regulation of neurotransmitters. PG inhibited the uptake of GABA, glutamate, dopamine, noradrenaline, and seratonin. In addition, PG may accelerate the process of nerve fibre production and maintenance. Nerve Growth Factor (NGF), a protein that plays an important role in the development and maintenance of sympathetic neurones, was increased in embryonic chick cells when exposed to PG saponins. (3) • PG was shown to increase gastric, pancreatic, and biliary secretion. At the same time, it was shown to prevent and heal gastric ulceration. (3) • PG may have a role in the treatment and prevention of cardiovascular disease. In the first instance, it normalised blood circulation. Several of the saponins increased contractile force of the heart. Some of the Ginsenosides caused vasodilatation, increasing peripheral blood flow to the fingertips and brain. (3)• PG also diminished risk factors associated with the development of atherosclerosis. PG reduced serum cholesterol levels. Rabbits fed a high cholesterol diet and treated with Ginseng saponins had reduced serum cholesterol levels, lower ratios of cholesterol to phospholipids, elicited less fatty infiltration of the liver, and diminished the penetration of cholesterol into aortic tissue. This resulted in less atherosclerotic alteration and prevented the occurrence of atheroma in the aorta. Research went onto demonstrate PG reduced the atherogenic index. (3) In addition, platelet aggregation and fibrin production was inhibited by PG. (3) • PG increased erythrocyte and haemoglobin counts. PG fractions induced erythropoietin production in the liver, kidney, spleen, and bone marrow. Ginseng fractions doubled the number of mitoses in both myeloid and elytroid cells, increased the numbers of nucleated cells in bone marrow, and reticulocytes in peripheral blood. Human erythrocytes were shown to have increased cellular metabolic activity when exposed to PG saponins. (3• In a variety of animal tests PG and its saponins have been found to inhibit inflammation. (3)• PG demonstrated blood sugar reduction activity. PG saponins have been shown to reduce blood sugar in both drug induced diabetic animals and genetically diabetic animals. It appears to work on several levels including stimulating the production of insulin. Recent work suggests that sugars contained in PG, the panaxans A?H also contribute to its reduction of blood sugar levels. (3) • Early work revealed PG promoted adrenal function. Research reveals that PG has the capacity to stimulate pituitary cells to increase production of ACTH and at the same time sit on cortical steroid receptors. Some of the Ginsenosides are more active at stimulating adrenal function than others. (3)
Adaptogen criterion: 1990–2003 This period of research has also been active. Hundreds of studies were undertaken and greastrides were made. With substantial evidence behind the efficacy of this particular adaptogen, some of the research took a different direction. Researchers began to look for cheaper ways to produce the PG saponins through cell cultures and other means. Simultaneously, work on its pharmacological effects continued. Studies conducted between 1990 and 2003 duplicated many of the findings about PG already mentioned in the review of research between 1969 and 1990. For example, this additional research confirmed the innocuous nature of Panax ginseng and its protective effect against cancer in extensive pre?clinical and epidemiological studies. (8)Some of the additional findings follow:• A case control study demonstrated PG might inhibit the Carcinogenesis associated with the transition from chronic hepatitis to hepatic cirrhosis. (10)• A study revealed that PG inhibited the development of mammary tumours induced by intra?mammary injections of N?methyl?N?nitrosourea in rats, brain and spinal cord tumours induced by transplacental administration of N?methyl?N?nitrosourea in rats, and uterine, cervical, and vaginal tumours induced by intra?vaginal applications of 7,12? dimethylbenza(a) anthracene in mice. PG also induced regression of adenamatous cystichyperplasia of the endometrium in human patients. (11)• Research indicated the supplementation with antioxidants, specifically PG, might protect smokers from oxidative damage and reduce the risk of cancer caused by free radicals associated with smoking. (16)• PG was shown to bolster immune activity. Specifically, it activated the innate immunityof cows infected with Staphylococcus aureus mastitis and contributed to their recovery.(12)• Used in combination with anti?HIV drugs, PG delayed resistance to these drugs in a human study. (13)• In a study of 227 volunteers, researchers found that following vaccination, participants given PG had a lower incidence of developing the common cold. With respect to the vaccination, antibody titres rose to an average of 171 units in the control group. PG treated patients displayed an average titre of 272 units. (18) • In another study involving 60 healthy volunteers, PG was found to increase immune activity and was deemed an immunomodulator. (24) • A study involving 625 patients revealed that patients treated with PG experienced an improvement of quality of life index in a physically and mentally stressed population. (17) • In a study involving 46 healthy male sports teachers, PG increased the subjects work capacity by improving muscular oxygen utilisation. (22) • In a study involving 24 elderly outpatients suffering from alcohol or drug induced hepatic?toxicity, PG improved the detoxifying activity of the liver. (25) • PG demonstrated effectiveness in the treatment of erectile dysfunction in 45 clinically diagnosed men. (5) • Administration of PG in rats resulted in a reduction of bile flow and bile secretion of total lipids and cholesterol, while it increase the secretion of proteins in a dose dependent manner. The drug may be of use in preventing gallstone development. (6) • PG improved secondary memory performance, improved speed of performing memory tasks, and accuracy of attention tasks in twenty healthy young adults. (7)• PG improved aspects of human mental health and social functioning after 4 weeks of therapy. (9)• PG improved vascular endothelial dysfunction in patients with hypertension. (14) • PG was found to improve the signs and symptoms of symptomatic post?menopausal women. (15)• In a study involving 36 non?insulin dependent patients, patients treated with PG experienced elevated mood, improved psychophysical performance, and reduced fasting blood glucose activity. In a higher dose group, patients experienced improved glycated haemoglobin, serum PNP, and physical activity. The conclusion was that PG might be a useful adjunct in the treatment of non?insulin dependent diabetes. (19)• In a study involving 46 patients with class IV cardiac function, participants given PG experienced an improvement in hemodynamical and biochemical indices. The effect amongst patients given both PG and digoxin was an even more pronounced improvement. (20)• In a study involving 30 mitral valvular surgical patients, PG had a protective effect on myocardial ischemia and reperfusion injuries following open?heart surgery. (21) • In a study involving 358 persons aged 50–85 years, PG had an anti?senility effect improving memory, raising white blood cell counts, organic immune function, function of hypophyseal?gonadalaxis, adrenal cortex function, and coronary heart disease with angina pectoris. (23)
Conclusion Panax ginseng complies with the criterion set out by Brekhman for an adaptogen and subsequent researchers have substantiated his finding. Evidence supports its use in raising general resistance and there is evidence that suggests it may be of use in other specific circumstances.
PG and heart disease There is evidence that PG has a role in preventing heart disease. As already noted, it contains anti?oxidants that may reduce free radical damage to cardiovascular tissues. (1–2, 16) In addition,
research has demonstrated it reduces cholesterol and blood pressure levels. (3) The reduction in these damaging influences may impede the development of atherosclerosis. (3) In addition, the drug demonstrated an ability to reduce the incidence of reperfusion injury to the heart muscle(21)
PG and viral disease PG has demonstrated the ability to raise resistance to infectious disease through immune
stimulation. (1–2) It has been shown to reduce the incidence of hepatic carcinoma in the patients in transition from chronic hepatitis to cirrhosis. (10) It has also been shown to reduce the anti?HIV drug resistance when used in conjunction with certain HIV anti?retro?viral drugs. (13)
PG and cancer PG has demonstrated the ability to inhibit Carcinogenesis and to increase resistance to existing cancer. (1–2, 8, 10–11) The action in both instances is complex. In addition, the drug has been shown to increase resistance to radiation and toxic chemicals, which suggest it may have a role as man adjunct in cancer therapy. (1–2)References for Panax ginseng 1. Brekhman, II and Dardymov, IV. Pharmacological Investigation of Glycosides from Ginseng and Eleutherococcus. II. Lloydia, March 1969, Volume 32, Number 1. P. 46–51. 2. Brekhman, II and Dardymov, IV. New Substances of Plant Origin Which Increase Nonspecific
Resistance. Annual Review of Pharmacology. Henry Elliott, Editor. Annual Reviews, Inc. 1969. P. 419–430. 3. Hikino, Hiroshi. Traditional Remedies and Modern Assessment: The Case of Ginseng. Hiroshi Hikino. The Medicinal Plant Industry. CRC Press. Chapter 11. P. 149–166. 4. Duke, J. Handbook of Phytochemical Constituents of GRAS drugs. CRC Press. P. 424. 1992 5. Hong B et al. A double blind crossover study evaluating the efficacy of Korean red ginseng in patients with erectile dysfunction: a preliminary report. Journal of Urology 2002 Nov; 168(5): 2070–3. From PubMed abstracts. 6. Salam OM et al. The effect of ginseng on bile?pancreatic secretion in the rat. Increase in proteins and inhibition of total lipids and cholesterol secretion. Pharmacology Research 2002 Apr; 45(4): 349–53. From PubMed abstracts. 7. Kennedy DO et al. Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and ginkgo/ginseng combination to healthy young adults. Physiol Behav 2002 Apr 15; 75(5): 739–51. From PubMed abstracts. 8. Yun TK. Panax ginseng?a non?organ specific cancer preventative? Lancet oncology 2001 Jan; 2(1): 49–55. From PubMed abstracts. 9. Ellis JM et al. Effects of Panax ginseng on quality of life. Annals of Pharmacotherapy 2002 Mar; 36(3): 375–9. From PubMed abstracts 10. The Ginseng HCC chemopreventive study Osaka group. Study on chemoprevention of hepatocellular carcinoma by ginseng: an introduction to the protocol. Journal of Korean Medical Science 2001 Dec; 16 Suppl: S70–4. From PubMed abstracts. 11. Bespalov VG et al. Chemoprevention of mammary, cervix and nervous system Carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the oesophagus and endometrium. Journal of Korean Medical Science 2001 Dec; 16 Suppl: S42–53. From PubMed abstracts. 12. HU S et al. Effect of subcutaneous injection of ginseng on cows with subclinical Staphylococcus aureus mastitis. J Vet Med B Infect Dis Vet Public Health 2001 Sep; 48(7): 519–28. From PubMed abstracts. 13. Cho YK et al. Long term intake of Korean red ginseng in HIV?1 infected patients: development of resistance mutation to zidovudine is delayed. International Immunopharmacology 2001Jul; (7) 1295–1303. From PubMed abstracts. 14. Sung J et al. Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. American Journal of Chinese Medicine 2000; 28(2): 205–16. From PubMed abstracts. 15. Wiklund IK et al. Effects of a standardised ginseng extract on quality of life and physiological parameters in symptomatic post menopausal women; a double blind, placebo controlled trial. International Journal of Clinical Pharmacology Res 1999; 19(3): 89–99. From PubMed abstracts. 16. Lee BM et al. Inhibition of oxidative DNA damage, 8?OhdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, betacarotene, and red ginseng). Cancer Letter 1998 Oct 23; 132 (1–2): 219–27. From PubMed abstracts. 17. Caso Marasco A. et al. Double Blind study of a multivitamin complex supplemented with ginseng extract. Drugs Experimental Clinical Research 1996; 22(6): 323–9. From PubMed abstracts. 18. Sotaniemi EA at al. Ginseng therapy in non?insulin dependent diabetic patients. Diabetes Care 1995 Oct; 18(10): 1373–5. From PubMed abstracts. 19. Ding DZ et al. Effects of red ginseng on the congestive heart failure and its mechanism. Zhongguo Zhong Xi Yi Jie He Za Zhi 1995 June; 15(6): 325–7. From PubMed abstracts. 20. Zhan Y et al. Protective effects of ginsenoside on myocardial ischemia and reperfusion injuries. Zhonghua Yi Xue Za Zhi 1994 Oct; 74(10): 626–8,648. From PubMed abstracts. 21. Pieralisi G et al. Effects of standardised ginseng extract combined with dimethylaminoethanal bitartrate, vitamins, minerals, and trace elements on physical
performance during exercise. Clinical Therapy 1991 May–Jun; 13 (3): 373–82. From
PubMed abstracts. 22. Zhao, YZ. Anti?senility effect of ginseng rhizome saponin. Zhong Xi Yi Jie He Za Zhi. 1990. Oct; 10(10): 586–9, 579. From PubMed abstracts.
23. Scaglione F et al. Immunomodulatory effects of two extracts of Panax ginseng. Drugs
Experimental Clinical Research 1990. 16(10): 537–42. From PubMed abstracts.
24. Zuin M et al. Effects of a preparation containing standardised ginseng extract combined
with trace elements and multivitamins against hepatotoxin induced chronic liver disease
in the elderly. Journal of International Medical Reseach 1987 Sep–Oct; 15(5): 276–81. From
25. You Kang H ET al. Effects of ginseng ingestion on growth hormone, testosterone, and insulin like growth factor 1 responses to acute resistance exercise. Journal of Strength
Conditioning Research 2002 May; 16(2):179–83. From PubMed abstracts.
26. Engels HJ et al. Effects of ginseng supplementation on supramaximal exercise
performance and short term recovery. Journal of Strength Conditioning Research 2001 Aug; 15(3): 290–5. From PubMed abstracts.
Crassulaceae Stone Crop
Part used Root
Chemical constituents Significant phytochemicals include salidroside, rosarin, rosavin, rosin, rosiridin, 5% essential oil (monoterpene hydrocarbons, monoterpene alcohols, straight chain aliphatic alcohols, primary oils including n?decanol, geraniol, and 1,4?p?menthadien?7?ol). (3)
History Rhodiola rosea is a member of the Sedum family and indigenous to the northern parts of Ireland, Scotland, Scandinavia, and Russia. A traditional medicine in Russia and Scandinavia, the drug is used to increase physical endurance, combat weakness, improve work capacity, and induce longevity. Medically, it is used to treat altitude sickness, fatigue, debility, depression, anaemia, impotence, gastrointestinal affections, infections, nervous disorders, infertility, cold, flu, tuberculosis, and cancer. Intriguingly, the Vikings used the drug to enhance physical endurance and strength. Linnaeus, the famous botanist, discussed its use in hernia, leucorrhoea, hysteria, and headache. Rhodiola rosea (RR) was introduced in the first Swedish Pharmacopoeia published in 1755. (22) Though those that had a local supply knew RR, it does not appear to have been an item of commerce. Gerard, an English drugalist working in 17th century London who was familiar with many foreign drugs, had little to say of it. “There is little extent of the faculties of Rosewort: but this I have found that if the root be stamped with oile of roses and laid to the temples of the head, it easeth the paine of the head.” (20) The drug remained a local remedy until the 1960’s when the Russian adaptogen researchers began investigating it for potential adaptogen activity. Between 1960 and present, over 180 pharmaceutical, phytochemical, and clinical studies have been conducted on Rhodiola rosea. (22)
Adaptogen criterion Applying Brekhman’s criterion to Rhodiola rosea (RR), it is clear that it exhibits the properties of an adaptogen in the following studies:
In vitro and animal studies • RR was found to be safe in acute and sub?acute toxicity studies. (13) • RR increased non?specific resistance of fresh water snail embryos against environmentally induced stress. (8) • RR increased resistance to free radical damage by acting as a free radical scavenger. (1) • RR reduced hyopoxia induced pancreatic injury either by increasing intracellular oxygen diffusion or by acting as an anti?oxidant. (4) • RR decreased the oxygen consumption of myocardium and oxygen consumption index, decreased coronary artery resistance, and had no effect on coronary blood flow in anaesthetised dogs. (5) • RR reduced stress induced cardiac damage. The cardioprotective and anti?stress effects are associated with limited adrenergic effects on the heart. (18) • RR had an anti?tumour and anti?metastatic effect in the Lewis lung cancer model in mice (potentiated cyclophosphamide). (7) • RR demonstrated a 90% inhibition rate of mutagenicity in Ungernia victoris cultured cells. (12) Shown to act as antimutagenic drug in bone marrow of cells of mice due to its ability to raise the efficiency of the intracellular DNA repair mechanism. (15) • RR reduced the toxicity and liver damage associated with the anti?tumour drug Adriamycin without reducing efficacy of the anti?tumour drug. (19) • RR normalised gastric functions, regardless of the nature of the perversion, in an animal model using cisplatin induced alterations. (13) • RR showed a marked preventative antiarrythmic effect when adrenaline and CaC12 were administered to rats. (14,16)
Human studies In a series of human studies, RR also possessed Brekhman’s adaptogenic properties. Namely, Rhodiola rosea: • Improved superficial bladder cancer by improving characteristics of the urothelial tissue integration, parameters of leukocyte integrins, and T?cell immunity. (17) • Reduced fatigue in a double blind cross over study of healthy physicians working night shifts. (9) • Reduced fatigue of students associated with the stress of examination periods. (10) • Increased the amount of veloergometric work accomplished, increased kinesthesiometric sensitivity, and increased the general condition. It also decreased the levels of psychic fatigue and situation anxiety. (11) • Increased erythropoiesis during sleep deprivation. (2)
Conclusion In many senses, Rhodiola rosea represents a classic tonic drug. It was used to increase work performance, fertility, and to remedy the signs and symptoms of ageing. It was also used to bolster those with failing health. From a research perspective, Rhodiola rosea complies with all the criterion set forth by Brekhman for an adaptogen. As such, there is evidence to support its use in raising resistance to stressors. References for Rhodiola rosea 1. Pieroni A et al. In vitro antioxidant activity of non?cultivated vegetables of ethnic Albanians in southern Italy. Phytotherapy Research 2002 Aug: 16(5): 467–73. From PubMed abstracts. 2. Probalova NV, Mechanisms underlying the effects of adaptogens on erythropoiesis during paradoxical sleep deprivation. Bulletin of Experimental Biology and Medicine 2002 May; 133(5): 428–432. From PubMed abstracts. 3. Rohloff, J. Volatiles from rhizomes of Rhodiola rosea, Phythochemistry 2002, March: 59: (6): 655–61. From PubMed abstracts. 4. IP, SP et al. Association of free radicals and the tissue renin?angiotensin system: prospective effects of rhodiola, a genus of Chinese Drug, on hyopoxia induced pancreatic injury. JOP 2001 Jan; 2(1): 16–25. From PubMed abstracts. 5. Zhang et al. The effect of Rhodiola capsules on oxygen consumption of myocardium and coronary artery blood flow in dogs. Zhongguo Zhong Yao Za Zhi 1998 Feb; 23(2): 104–6. From PubMed abstracts. 6. Ganzera M et al. Analysis of the market compounds of Rhodiola rosea by reverse phase high performance liquid chromatography. Chem Pharm Bull (Tokyo) 2001Apr; 49(4): 465–7. From PubMed abstracts. 7. Razina TG et al. Medicinal plant preparations used as adjuvant therapeutics in experimental oncology. Eksp Lin Farmakol 2000 Sept–Oct; 63(5): 59–61. From PubMed abstracts. 8. Boon?Niermeirjer EK ET al. Phyto?adaptogens protect against environmental stress induced death of embryos from the fresh water snail Lymnae stagnalis. Phytomedicine 2000 Oct; 7(5): 389–99. From PubMed abstracts. 9. Darbinyan V et al. Rhodiola rosea in stress induced fatigue?a double bind cross over study of a standardised extract SHR?5with a repeated low dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine 2000 Oct; 7(5): 365– 71. From PubMed abstracts. 10. Spasov AA et al. A double blind, placebo controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR?5 extract on the fatigue of students caused by stress during an examination period with a repeated low dose regimen. Phytomedicine 2000 Apr; 7(2): 85–89. From PubMed abstracts. 11. Spasov AA et al, The effect of the preparation rodakson on the psychopathophysiological and physical adaptation of students to an academic load. Eksp Klin Farmakol 2000 Jan– Feb; 63(1); 76–78. From PubMed abstracts. 12. Duhan OM et al. The antimutagenic activity of biomass extracts from the cultured cells of medicinal plants in the Ames test. Tsitol Genet 1999 Nov–Dec; 33(6):19–25. From PubMed abstracts. 13. Rege NN et al. Adaptogenic properties of six rasayana drugs used in Ayurvedic medicine. Phytotherapy Research 1999 June; 13(4): 275–91. From PubMed abstracts. 14. Maimeskulova LA et al. The anti?arrhythmia action of an extract of Rhodiola rosea and of n?tyrosol in models of experimental arrhythmia’s. Eksp Klin Farmakol 1998 Mar–Apr; 61(2): 37–40. From PubMed abstracts. 15. Salikhova RA et al. Effect of Rhodiola rosea on the yield of mutation alterations and DNA repair in bone marrow cells. Patol Fiziol Eksp Ter 1997 Oct–Dec; (4): 22–4. From PubMed abstracts. 16. Maimeskulova, LA et al. The participation of the mu, delta, and kappa opioid receptors in the realisation of the anti?arrhythmia effect of Rhodiola rosea. Eskp Lkin Farmakol 1997 Jan–Feb; 60(1): 38–39. From PubMed abstracts. 17. Bocharova AO et al. The effect of Rhodiola rosea extract on the incidence of recurrences of a superficial bladder cancer. Urol Nefrol 1995 Mar–Apr; (2): 46–7. From PubMed abstracts. 18. Maslova LV et al. The cardioprotective and anti?adrenergic activity of an extract of Rhodiola rosea in stress. Eksp Klin Farmakol 1994 Nov–Dec; 57(6): 61–3. From PubMed abstracts. 19. Udintsev SN et al. The enhancement of the efficacy of Adriamycin by using hepatoprotectors of plant origin in metastases of Ehrlich’s adenocarcinoma to the liver in mice. Vopr Onkol 1992; 38(10):1217–22. From PubMed abstracts. 20. Johnson, Gerard. The herbalor general history of plants. 1633. London. P. 532. 21. Ye at al. Effect of Salidroside on cultured myocardial cells anoxia/re?oxygenation injuries. Zhuongguo Yao Li Xue Bao. 1993. Sep; 14(5)P. 424–6. From PubMed abstracts. 22. Brown et al. Rhodiola: A phytomedical review. Drugalgram 2002: 56:40–52.
Chinese matrimony vine
Plant, berry, seed.
Significant phytochemicals include angeloulgomisin?O?Q, angeloulisogomisin?O,
benzoylisogomisin, deoxyschisandrin, epigomisin?O, gomisin A?R, pregomisin, schisantherim?D,
schizandrin, gamma?schizandrin, schizandrol, steroids, and tigloylgomisin?P. (1)
The drug is indigenous to China and has been used as a tonic since antiquity. One of the
fundamental drugs in Traditional Chinese Medicine, many parts of the plant are used
medicinally. The stem is decocted into a mucilaginous liquid that is used in cough, dysentery,
and gonorrhoea. The fruit is considered anti?tussive, aphrodisiac, stimulant, and tonic. It is used
in amnesia, asthma, cough, diabetes, diarrhoea, dysentery, insomnia, night sweats, polyuria,
premature ejaculation, spermatorrhea, stridor, and tuberculosis. The seed is used in cancer. (10)
Chinese tonic preparations frequently contain this drug.
Although Brekhman identified Schizandra chinese (SC) as an adaptogen, he did not research this
drug. Reviewing the literature it is clear that SC fits the parameters of an adaptogen as defined by
Brekhman?s criterion; it is non?toxic, non?specific, and normalises function regardless of the
pathology’s trajectory. Examples that demonstrate this are as follows:
• SC was determined to be non?toxic and safe. (9)
• The crude drug reduced hepatotoxicity associated with an Alzheimer drug in a mouse
study (2) and reduced hepatotoxicity of carbon tetrachloride intoxication. (3)
• The crude drug acts as a free radical scavenger which may contribute to its reported antiageing
effect. (4) Nine different lignan’s were determined to have anti?oxidant activity.
• The crude drug increased resistance to work and increased capacity to do work in test
• Gomisin A was found to inhibit tumour formation following exposure to tumour causing
• Gomisin A showed a suppressive effect against hepatocarcinogen caused tumour
formation in rats. (11)
• Rats, treated with Gomisin A, and then exposed to hepatotoxins, did not develop
massive hepatic cells necrosis or die. The result suggested that Gomisin A could be used
to prevent acute hepatic failure. (12) It also prevented immunologically induced hepatic
failure in the guinea pig. (13) Several other animal studies demonstrated that Gomisin A
protected the liver from chemical damage. (14–16)
• Schisandrin was shown to prevent cerebral toxicity in mice exposed to a cerebra?toxic
• Gomisin and Schisandrin were determined to have an anti?HIV activity. (21)
• Crude extracts lowered levels of serum glutamic pyruvic transaminase(sgpt) caused by
hepatitis. The fruit exhibited a therapeutic effect in viral and chemical hepatitis.
Schisandrol was the most effective in lowering sgpt levels. In mice, the drug reduced
carbon tetrachloride liver toxicity.(10) Schisantherin A–D were found to normalise liver
enzyme assays in patients suffering from chronic hepatitis. (8)
• Soviet research indicated that in low doses the crude drug acted as a Central Nervous
System stimulant and in higher doses as a Central Nervous System depressant. (10)
• An analogue of Schisandrin was effective in reducing liver impairment in acute and
chronic liver disease in human patients. (22)
• Gomisin A inhibited inflammation. (7)
• Soviet research indicated the drug regulated cardiovascular function. (10) Schisandrin B
prevented myocardial ischemia?reperfusion injuries in the rat heart. (19)
• Schisandrin B diminished the hepatic?toxicity associated with a toxic compound and
enhanced cognitive function in mice. The conclusion was that Schisandrin B might be
useful in Alzheimer’s therapy to diminish toxicity associated with Alzheimer’s drugs and
to improve mental function. (18)
• Schisandrin B reduced carbon tetra?chloride hepatotoxicity in streptozotocin induced
diabetic rats. (20).
Schizandra chinensis is one of the most widely used tonic drugs in Chinese medicine. It is seen as
a fortifying agent, strengthening the weak, the ill, and the aged. As shown, SC complies with
adaptogenic criterion set forth by Brekhman and there is evidence that the drug can be used to
raise resistance to stressors. In addition, as research reveals, it may be useful in certain specific
SC and Hepatitis
The drug may have a role raising resistance to chemically induced and viral hepatitis. The drug
has been shown to raise liver resistance to free radical damage, toxic compounds, and
inflammatory changes in animal studies. (2–4, 6, 11–16, 18, 20, 22) The same studies also suggest
it may have a role in preventing the liver damage often associated with chronic hepatitis.
SC and risk reduction in drug therapy
The drug may have a role in reducing the toxicity associated with certain drug therapies as it
raises resistance to liver toxicity in healthy and compromised animals. (7,20) A study using mice
demonstrated that the liver toxicity associated with one Alzheimer drug was reduced with the
administration of SC. Though liver damage was reduced, the efficacy of the Alzheimer drug was
SC and chemical exposure
Similarly, SC may have a role in raising liver resistance to toxic compound exposure in workers
routinely exposed to toxic chemicals and to those incidentally exposed. Indeed, the crude drug
and constituents have been shown to reduce liver toxicity associated with exposure to hepatotoxic
substances. (2–4, 6, 11–16, 18, 20, 22)
References for Schizandra chinensis
1. Duke, James. Handbook of Phytochemical constituents of GRAS drugs. 1992. CRC Press.
2. Pan SY et al. Schisandrin B protects against tacrine and bis?(7)?tacrine induced
hepatotoxicity and enhances cognitive function in mice. Planta Medica 2002 March; (3):
217–20. From PubMed abstracts.
3. Zhu M et al. Improvement of phase I drug metabolism with Schisandra chinensis against
CCL4 hepatotoxicity in a rat model. Planta Medica 2000 Aug; 66(6): 521–5. From PubMed
4. Ip SP ET al. Schisandrin B protects against menadione induce hepatotoxicity by
enhancing DT?diaphorase activity. Mol Cell Biochem 2000 May; 208(1–2): 151–5. From
5. Azizov AP et al. The effect of elton, leveton, and adapton on the work capacity of
experimental animals. Eksp Klin Farmakol 1998 May–June; 61(3):61–3. From PubMed
6. Lu H et al. Anti?oxidant activity of dibenzocyclooctene lignans isolated from
Schisandraceae. Planta Medica 1992 Aug: 58(4): 311–3. From PubMed abstracts.
7. Yasukawa K et al. Gomisin A inhibits tumour promotion by 12?O?tetradecanoylphorbol?
13?acetate in two?stage Carcinogenesis in mouse skin. Oncology 1992; 49(1): 68–71. From
8. Liu et al. Studies on the active principles of Schisandra. The structures of schisantherin AE.
Sci Sin 1978 Jul–Aug; 21(4): 483–502. From PubMed abstracts.
9. Brekhman, II and Dardymov, IV. New Substances of Plant Origin Which Increase
Nonspecific Resistance. Annual Review of Pharmacology. Henry Elliott, Editor. Annual
Reviews, Inc. 1969. P. 419–430.
10. Duke, James and Ayensu, Edward. Medicinal Plants of China. Reference Publications.
Michigan. 1985. P. 422.
11. Miyamoto et al. Effects of Gomisin A on hepatocarcinogenesis by 3’?methyl?4?
dimethyaminoazobenzen in rats. Jpn J Pharmacol 1991 Sep; 57(1):71–7. From PubMed
12. Mizoguchi et al. Effect of Gomisin A in the prevention of acute hepatic failure induction.
Planta Medica 1991Aug; 57(4): 320–4. From PubMed abstracts.
13. Mizoguchi et al. Effect of gomisin A in an immunologically induced acute hepatic failure
model. Planta Medica 1991 Feb; 57(1): 11–4. From PubMed abstracts.
14. Nagai et al. The effect of gomisin A on immunologic liver injury in mice. Planta Medica
1989Feb; 55(1): 13–7. From PubMed abstracts.
15. Takeda et al. Effects of gomisin A, a lignan component of Schizandra fruits, on
experimental injuries and liver microsomal drug metabolising enzymes, Nippon
Yakurigaku Zhashi 1986 feb; 87(2): 169–87. From PubMed abstracts.
16. Maeda et al. Effects of gomisin A on liver functions in hepatoxic chemical treated rats.
Jpn J Pharmacol 1985 Aug; 38(4): 347–53. From PubMed abstracts.
17. Ko et al. Schisandrin B protects against tert?butylhydroperoxide induced cerebral toxicity
by enhancing glutathione antioxidant status in mouse brain. Mol Cell Biochem 2002 Sep;
238 (1–2): 181–6. From PubMed abstracts.
18. Pan et al. Schisandrin B protects against tacrine and bis?(7)?tacrine induced
hepatotoxicity and enhances cognitive function in mice. Planta Medica 2002 Mar; 68(3):
217–20. From PubMed abstracts.
19. Yim et al. Methylenedioxy group and cylcoootadiene ring as structural determinants of
schisandrin in protecting against myocardial ischemia?reperfusion injuries in rats.
Biochemical Pharmacology 1999 Jan 1; 57(1): 77–81. From PubMed abstracts.
20. Mak et al. Alterations in susceptibility to carbon tetrachloride toxicity and hepatic
antioxidant/detoxification system in streptozotocin induced short term diabetic rats:
effects of insulin and schisandrin B treatment. Mol Cell Biochem 1997 Oct; 175(1–2): 225–
32. From PubMed abstracts.
21. Chen DF et al. Anti?Aids agents?XXVL. Structure activity correlations of Gomisin?G
related Anti?HIV lignans from Kadsura interior and of related synthetic analogues.
Bioorg Med Chem 1997Aug; 5(8): 1715–23. From PubMed abstracts.
22. Akbar et al. Effectiveness of the analogue of natural Schisandrin (HpPro) in treatment of
liver disease: an experience in Indonesian patients. Chin Med J (Eng) 1998 Mar; 111(3):
248–51. From PubMed abstracts.