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.
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