Ginseng: A new Look at an old Story

Jen-Hsou Lin1 and Leang-Shin Wu
Department of Animal Science, National Taiwan University,
Taipei, Taiwan, Republic of China
1e-mail: jhlin@ccms.ntu.edu.tw

Abstract

Ginseng has been used in traditional Chinese medicine for thousands of years as an aid to prevent and treat many kinds of disease. It has been called a panacea. After intensive pharmacological investigations during the last 50 years, ginseng has developed a great reputation for marked effects on the body. From the viewpoint of preventive medicine, ginseng tonics can stimulate the body's defence system. This aids the body to overcome some insults and to adapt to stressful environments. This paper will review the source, chemistry, pharmacology and clinical applications of ginseng.

Key words: ginseng, traditional Chinese medicine, herbs, resource, chemistry, pharmacology, therapy

Introduction

The use of ginseng has a long rich history in traditional Chinese medicine (TCM). Prized by TCM practitioners and their patients as an effective tonic, ginseng has been in use since the Han Dynasty some 2000 years ago and perhaps even longer. An extensive amount of literature focuses on the use of this venerable herb. This ranges from anecdotal descriptive clinical observations, to detailed studies of individual constituents by modern techniques of molecular biology. One also finds folklore and romanticism that offers an illuminating glimpse into a system of beliefs and practices that form the background to the study of ginseng.

Forty years ago, two wonderful classmates and I attended a 50 km race. As we were only 12 years old, that was quite a long distance for us. On the morning of the race my mother gave me a piece of yellow twig about 2 g in weight. She told me to chew it if I became very tired. I was so excited, I forgot to ask her why. I put the twig in my pocket. There were thousands of competitors and despite being so young, we ran very well for the first 10 km. My body was so wet with sweat that the twig became soft. I swallowed it quickly without chewing it thoroughly. About 10 minutes later, a strange thing happened to me. I felt so sleepy that I sat down by the side of the road and fell asleep quickly. This was in spite of my friends trying to wake me. Several minutes later, I woke up and felt extremely thirsty. After drinking 2 bottles of water, I became wide awake and began running again. I was running better and better, but my two partners were fading. I held them up with my arms during the last 10 km and we finished the whole distance (50 km) within 10 hours. The next day, I went to school in good spirits even though my muscles ached, but my partners were too tired to attend. I wondered about this event for many years because we were in the same physical conditions. Why should I perform better? Finally, a patient's parent gave me a piece of ginseng as a reward after donating blood to her daughter during an emergency. At that time, I understood that the twig my mother gave me was ginseng. This illustrates ginseng's anti-fatigue effect.

In the 1950's, a Russian doctor, Brekhman, showed this effect by studying soldiers during exercise. He found that soldiers who consumed ginseng prior to exercise performed much better than those who did not. There was a record in Sou-Song's book "Chia-You-Tou-Ching" (1062) suggesting a test for true ginseng. The herb was given to one individual and not to the other. They were then asked to quickly walk for 1-2 miles. The individual who received the ginseng should not show any physical changes, but the other person should be panting and exhausted. This is an example of an ancient bioassay technique. You may try to prove the efficacy of ginseng yourself. The results may change your opinion of ginseng or even TCM. Today, ginseng preparations are gradually gaining wide acceptance in small animal medicine.

Source

In 1842, botanist Carl Mayer named ginseng, the root of the arialaceous plant. The genus Panax derives its name from the Greek pan (all) and akos (healing) - literally panacea or all-healing. Chinese doctors rely heavily on ginseng, but western scientists have been sceptical about its therapeutic values to its lack of specificity and broad effects. Panax ginseng (Asian ginseng, mainly from China and Korea) and P. quinquefolius (American ginseng, primarily from Canada and north America) are the common forms of ginseng. P. notoginseng and P. japonicus are less common varieties. Eleutherococcus senticosus (Siberian ginseng, a member of the Ariliaceae family), is another common preparation. It contains chemically distinct glycosides (eleutherosides).

Rapidly increasing international demand has led to special efforts to cultivate ginseng in China, Korea, Canada, north America and Australia. These include the development of culture varieties by selection, field cultivation, re-utilisation of abandoned ginseng plantations, ginseng cultivation under forestry and prevention and treatment of the diseases and pests of ginseng. In respect to the tissue culture of ginseng, the development of the callus tissue, solid medium culture, liquid medium culture and submerged culture of ginseng callus have all been developed. Ginseng callus contains saponins (ginsenosides) similar to those of the roots, indicating that the callus has similar pharmacological activities

Roots of plants 5-7 years old are either air-dried to yield "white ginseng", or steam-treated for 2-4 hours to yield "red ginseng". In clinical use, white ginseng usually is used as a Yin-tonic and red ginseng as a Yang-tonic

Chemistry

Using column- and thin layer- chromatography, Russian and Japanese scientists were first to report the separation and isolation of ginseng saponins (ginsenosides). Ginsenosides are the main active constituents of ginseng. The root, root-stock, stems, leaves, flowers and flower-buds of the ginseng plant contain more than 30 ginsenosides. Extracts from red and white ginseng contain different ginsenosides. The accepted nomenclature of the individual saponins named Rx (x=o, a, b1, b2, c, d, e, f, g1, g2 .) is based on the sequence of spots detected after silica gel thin layer chromatography. Ginsenosides are tri-terpenoid glycosides of the dammaran series. They can be divided into three types according to the characteristics of their chemical structure: oleanolic acid, panaxadiol and panaxtriol types. Ginsenoside Ro is due to oleanolic acid saponin, while the other ginsenosides are due to panaxadiol and panaxatriol saponins. The chemical structures of these ginsenosides have been detected by IR, MS, NMR and chemical reactions.

Besides ginsenosides, ginseng also contains other active compounds such as alkaloids, maltol, volatile oil and polysaccharides.

Pharmacology

Early studies revealed that ginseng possesses biomodulatory effects on the higher centres of the central nervous system, facilitating both physical and mental activities. It has a noteworthy effect on the endocrine system. Recent experimental and clinical studies concluded that ginseng has a wide range of effects. These include a remarkable anti-shock effect in circulatory failure and a modulatory effect on the immune system, cellular metabolism, and endocrine functions. Though the mechanism of ginseng action remains unclear, the ginsenosides are the main active compounds. An extensive amount of literature deals with its effects on the CNS (memory, learning and behaviour), neuroendocrine functions, carbohydrate and lipid metabolism, immune function and the cardiovascular system. Reports are often contradictory. Perhaps this is because the ginsenoside contents of ginseng or root extracts are different depending on the method of extraction, subsequent treatment, or even the season of its collection. The following is a summary of some of the recent important findings in ginseng research. Readers may refer to the references for the details.

Adaptogenic effect

TCM considers ginseng to have stimulatory effects on physical capacity, alertness, and powers of concentration, especially in the elderly and those recovering from illness. Brekhman, a pioneer in the experimental evaluation of ginseng, used the term "adaptogen" to describe these non-specific tonic effects of ginseng and other members of the Ariliaceae family. Ginseng reportedly increased resting oxygen uptake and oxygen transport in elderly subjects. It also significantly increased the capacity for mental arithmetic and logical deduction in healthy normal subjects. Several clinical reports suggest that ginseng increased physical performance and reduced fatigue in human subjects.

Cardiovascular actions

Cardiovascular effects of ginseng and individual ginsenosides have been studied extensively. Many reports describe a transient vasodilator action, which in some cases is followed by vasoconstriction and an increase in blood pressure. Several authors have implicated the adrenergic nervous system in the cardiovascular effects of ginseng. It has been reported that the panaxatriols, particularly Rg, reduced ACh-evoked release of catecholamines from bovine adrenal chromaffin cells. Extrapolating from the data, the authors suggest that ginseng may reduce elevated circulating catecholamine concentrations associated with various forms of human stress.

Immune modulation

Until recently, little was known of the local effects of ginseng on the immune system. Some studies with human lymphocytes, activated by phytohaemagglutinin or concanavalin-A, showed that Rg1 could promote mitosis. However Rb1 had the opposite effect inhibiting mitosis and DNA synthesis of the stimulated lymphocytes.

Polysaccharides of ginseng were found to significantly increase phagocytosis of the reticuloendothelial system and the production of antibodies. They caused an increase in serum complement content in guinea pigs and raised the serum IgG level in mice. They also increased the number of B-lymphocytes and T-lymphocytes.

Neurotropic activity

Ginsenoside Rg1 and Rb1 were found to possess neurotropic activity. The two components improve memory and learning, both in normal animals and in animals whose cognitive functions are impaired. The mechanism is a multiple biological effect: Rg1 and Rb1 influence brain cholinergic mechanism, increase the synthesis and release of ACh, decrease brain 5-HT level, promote brain nucleotide and protein metabolism, and decrease and clear oxygen free radicals. Thus, there is reason to conclude that ginseng can be a neurotropic drug.

Aphrodisiac action

Ginseng has long been reported to have aphrodisiac properties. It is likely that such effects reflect the non-specific tonic or adaptogen actions referred to above. However, recognition of importance of NO (nitric oxide) in the mechanism of penile erection led to consideration of the rabbit as a model. NO is released from non-adrenergic, non-cholinergic nerves. It relaxes both the human and rabbit penile corpus cavernosum, thus permitting penile erection. Since endothelial cells and perivascular nerves in the corpus cavernosum contain NO synthase, ginsenosides may relax the corpus secondary to the release of endogenous NO. By means of an in vitro superfusion technique, ginseng extract relaxed the corpus cavernosum in a concentration-dependent manner. It increased Ach-induced relaxation, and significantly enhanced tetrodotoxin-sensitive cavernosal relaxation in response to transmural nerve stimulation. These effects were attenuated significantly by inhibition of NO synthase. They were enhanced by superoxide dismutase, which is assumed to scavenge oxygen-radicals that would otherwise oxidise NO. The authors concluded that ginsenosides may release NO from endothelial cells and perivascular nerves in the corpus cavernosum, and speculate that the aphrodisiac effect of ginseng may be linked partly to release of NO.

Luteotropic activity

Luteotropic activity means there can be an increase in the progesterone production from luteal cells or an increase in the life span of the cells. It also implies gonadotropic activity that stimulates gonadal functions of animals. Almost no other plant material has been proven to have such activity. Most known materials with such activity are hormones isolated from animal tissues. We first provided evidence of the luteotropic activity of polysaccharides, isolated from ginseng flowers and leaves, by using a dispersed bovine luteal cell system in vitro. It suggests that these polysaccharides may be useful in the future in clinic settings.

Adverse effect

Generally speaking, ginseng is a very mild and non-toxic medicinal herb. The LD50 of ginseng in mice has been reported as 10-30g/kg. Long term treatment of rats, mice, dogs and rabbits caused very few observable signs of toxicity. There were no treatment-related changes in body weight, haematology or clinical chemistry after 90 days of daily administration of as much as 15 mg/kg ginsenosides to both male and female dogs. Despite the expectation of safety from such data, case reports of presumed ginseng toxicity continue to appear in the literature. There are reports of acute hypertension, together with side effects including behaviour stimulation, sleeplessness, diarrhoea, mastalgia and skin eruptions after a short course of ginseng treatment at high doses. As far as is known, there are no drug interactions with ginsenosides.

Clinical applications

Ginseng was a very valuable medicinal herb in the past. It was seldom used in animals in ancient China except in some special cases. Traditional veterinarians would use Dan-Seng (Codonopsis pilosula) or Sai-Seng (Adenophora tetraphylla) as a substitute, or some other tonic herbs such as Houng-Chi (Astragalus membranaceus), Dan-Choa (Ziziphus jujuba), Dan-Gau (Angelica sinensis), Chao-Kou-Lan (Gynostemma pentaphllum), or Yin-Yan-Hou (Epimedium brevicornum). Therefore the following reports are derived from human medicine in China.

Anti-ageing

Ageing is due to inborn processes, environmental factors and disease. Anti-ageing means prolonging the life span and a reducing the signs of ageing. Human subjects (n=327, aged 50-70 years old) took ginsenosides - 150mg/day for 2 months. The ginsenosides had marked effects on relieving the symptoms of ageing, adjusting the metabolism and improving physiological functions such as promoting memory, raising the amount of leukocytes and increasing immune functions.

Diabetes

Ginseng has been used to treat diabetes for a long time. It can lower blood sugar to some degree, which improves the general symptoms such as thirst and weakness. Thirty-seven diabetic patients were given oral ginsenosides, 50 mg, 3 times/day for 2 months. The general symptoms were improved and the blood sugar levels fell in 23/37 patients.

Cancer

Ginsenosides are useful anticancer agents and immune-stimulants. One hundred-one cancer patients with various types of cancer took an anti-cancer agent (such as cyclophosphomide, 50mg) and a ginsenosides (50 mg) mixture daily. In almost all patients, clinical symptoms were improved (better appetite, body weight increased, pain abated). Anaemia and leukocytopenia caused by the anticancer drug was improved.

Angiocardiopathy

Protective effects of ginsenosides on myocardial ischaemic and reperfusion injuries were investigated in thirty mitral valvular surgical patients. The patients were randomly divided into 3 groups. No saponin was used in the control group, which consisted of 11 patients. In the two treatment groups, the saponin and the ginsenoside Rb were added into the cardioplegis solution, respectively. During the operation, comparative studies were made of the pre- and post-operative cardiac functions with intraoperative transoesophageal echocardigraphy and with electromicroscopy of myocardial cells. Both total saponin and ginsenoside Rb had protective effects on myocardial ischaemic and reperfusion injuries in open heart surgery, and the effect of total saponin was even better than that of ginsenoside Rb.

Hepatitis

Infectious hepatitis is a common disease in the East and unfortunately, Chinese doctors have vast experience with the disease. Gan-Fu-Kang, which consists of ginseng saponin and saikosaponin in a ratio of 10/1, had a favourable therapeutic effect on chronic hepatitis B. The short-term effective rate in 360 patients was 88.6%; this was significantly higher than in the control group. The negative rate of HbsAG was 30%, which was also higher than the control.

Ulcer

The therapeutic effect of Wei-Kang-Ling, which consist of ginseng saponin and bee gum in a ratio of 1/2, was investigated in 465 peptic ulcer patients. After administration of the formula, the stool was examined for occult blood and a barium study was done. The pre- and post-treatment findings differed significantly. The total effective rate was 92.4%. In a double blind study, no significant difference was observed between Wei-Kang-Ling and cimetidine in 70 peptic ulcer patients. The side effects, such as headache, vertigo, depression and drug rash seen in the cimetidine group, were not observed in Wei-Kang-Ling group.

Adverse effects of glucocorticoid drugs

Under physiological conditions, ginseng saponin stimulates the hypophyseal-adrenal system and the secretion of glucocorticoid hormones. It also has a protective action on the hypophyseal-adrenal system under stress conditions or a glucocorticoid overdose. Clinical investigations have shown that ginseng saponin may alleviate the adverse effects due to the administration of large doses of glucocorticoids over a long period. The treatment of inflammation with the combined application of ginseng and glucocorticoid is recommended.

Erectile dysfunction

Since ancient China, ginseng has been used to maintain physical vitality and improved sexual performance. Thirty-three patients with borderline organic and psychological erectile dysfunction were studied: 23 took ginseng extract, 300 mg/day for 3 months, and the other 10 served as the placebo group. The clinical efficacy of the ginseng group was 66.7% on objective questionnaire and 72.2% on subjective analysis; this was significantly higher than in the placebo group.

 

Conclusion

Though some chemical constituents of ginsenosides have different pharmacological activities, these constituents were not widely applied clinically. In general, multiple constituents in ginseng mainly produce the wide range of therapeutic actions. In order to reasonably utilise these actions, we must make a great effort to investigate the therapeutic value of each constituent. Animal studies and veterinary practices will be needed to confirm the findings from human medicine.

Acknowledgements

We thank Drs. Edward Boldt (IVAS) and Phil Rogers (Dublin) for kind criticism in preparing this manuscript.

 

References