Panax Ginseng C.A.Meyer

GINSENG

 

 

                            
Kwang-Tae Choi

Korea Ginseng & Tobacco Research Institute

 

 

 

1. Introduction
   

   
    

   
    

2. Biology
   

 

 

1. Taxonomical View of Ginseng Plants
   
2. Botanical Characteristics of Cultivated Korean Ginseng Plants
   
3. Related Species
   
4. Distribution and Cultivation
   
5. Biotechnological Approaches for Micropropagation and Production of Active Principle
   
   1. Micropropagation
      
   2. Production of Ginsenosides by In Vitro Culture of Ginseng Cells
      

 

 

1. Chemistry
   

   
    

   
    

2. Active Components
   
   1. Ginsenoside (Ginseng Saponin)
      
   2. Other Active Components
      
3. Pharmacological Properties
   
   1. Effects of Ginseng on Hepatic Diseases
      
   2. Effects of Ginseng on Diabetes Mellitus
      
   3. Anticarcinogenic Effects of Ginseng
      
   4. Effects of Ginseng on the Cardiovascular System
      
   5. Antifatigue, Antistress and Anti-Aging Effects of Ginseng
      

 

 

1. References
   

 

 

 

 

1. Introduction
   

 

 

 

Ginseng, Panax ginseng C.A.Meyer, has traditionally been considered a medicinal

plant of mysterious powers and has several thousand years of history among Oriental people. Especially in Korea, China and Japan, ginseng has been recognized as the most prized medicine among all herbal medicines. Therefore, the Oriental people have traditionally used ginseng roots and extracts for geriatric, stomachic, aphrodisiac treatment, and tonic. From the pharmacological studies of animal and human beings for more than 30 years, the efficacy of ginseng, especially tonic effects, has been gaining popularity even in western countries. The term tonic refers to a drug meant for maintaining normal physical tone or restoring a diseased state to normal. Ginseng has been known to have a tonic effect and it is the general opinion of many investigators (Bittles, 1979; D.H.Zhuo, 1982; Brekhman and Dardymov, 1969) that ginseng has the effect of normalization of physical conditions, that is, maintaining individual homeostasis. The Korean workers, Oh et al. (1969) and Hong et al. (1969), have reported that in mice the saponin fractions potentiate hypnosis, retard the onset of cocaine-induced convulsions, reduce body temperature, and enhance the process of sexual behavior.

    Recently a number of scholars have paid attention to elucidate the efficacy of ginseng scientifically. Today I have a considerable amount of information about cultivation, breeding, biotechnology, composition, pharmacology properties, clinical demonstrations, and molecular biology. And it is now known widely as a health food all over the world.

    Nowadays Korea is the largest Panax ginseng producing and exporting country in the world. In 1999, about 25,000 households were engaged in the cultivation of ginseng over a total area of over 11,800 ha. The estimated amount of cultivated ginseng crops reached 13,000 tons, of this, 2,930 tons were exported to more than 60 countries. Therefore, ginseng, Panax ginseng C.A.Meyer, is the economically important plant in the world.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1. Biology
   

   
    

   
    

1. Taxonomical View of Ginseng Plants
   

   
    

   
    

   The systematic of ginseng plants is as follows:
   

Phylum                Embryophyta

Subphylum             Angiospermae

Class                 Dicotyledoneae

Subclass             Anchichylamyeae

Order                    Umbellifloreae

Family                     Araliaceae

Genus                     Panax

The scientific name of the Korean ginseng plant is Panax ginseng C. A. Meyer as

used world-wide. C. A. Meyer, who was a Russian, named the plants in 1843. Panax is a compound Greek word and pan denotes all, axos means cure, therefore Panax denotes cure all, and the word "ginseng" originated from the Chinese pronunciation of ginseng plants.

 

 

1. Botanical Characteristics of Cultivated Korean Ginseng
   

Plants

 

 

Ginseng is a perennial herb with flesh roots, an annual stem bearing a whorl of palmate compound leaves and a terminal simple umbel. Ginseng plants are basically self-pollinated plants. However, cross-pollination can be found also. Flowers that are wrapped prior to blooming show over 95% self-pollination, and the percentage of cross-pollination is thought to be low.

Flowers start to bloom when the plant is 3-year old. Ginseng flowers in the middle of May. It is general practice to collect the seeds once from 4-year old plants, and the flower buds are nipped off for better growth of the roots. The ripe red fruits are gathered two or three times in the middle of July (Fig. 1). The mature fruits usually contain two white-yellow seeds.

    It is believed that the berries that fall on the ground naturally are the most desirable for propagation. The ginseng seeds must be stratified with fine sand to promote embryo growth artificially because the embryo is immature when the seed is gathered. The optimum season for sowing on the nursery bed are transplanted in late March and early April, and harvested 3 to 5 years after transplanting the seedlings, that is, 4- or 6-year old roots are harvested (Fig. 2).

The roots are corpulent and they are composed of a taproot (or main root), two to five lateral roots, and fine roots. The roots are light yellowish white in color. The size and the shape of the root are varied with soil property, fertilizer, water content in soil, method of transplantation, climate, and germplasm. Especially, the growth of the root and its shape differ according to plant age. The roots are harvested when the plants are 4- to 6-year old, but younger roots do not exhibit complete maturity in the growth of the main and lateral roots. The only six-year old plant of ginseng has the rhizome, main and lateral roots grown with balance to a shape that resembles the human body. At 6 years, the rhizome becomes fat and the length of the main root is about 7 to 10 cm; the diameter of the main root is about 3 cm, and in addition it has many fat lateral roots, the total length being about 35 cm. The weight of this mature root is 70 to 100g, and some have been found weighing 300 to 500g per root.

Korean ginseng is a perennial plant which sprouts buds from its roots each spring, and whose leaves and stems dry up and die off each fall. At that time each year the trace of an insertion is left on the rhizome, the head of the root, and its shape varies from mortar shape to hollow shape. This rhizome is an important factor in the quality assortment process of ginseng's manufactured goods; therefore if this part is missing, it is judged as inferior quality or becomes a low-priced item. For this reason, special care is taken in handling. In particular, this rhizome is the special feature of Korean ginseng and it is used as a manufacturing index to distinguish Korean ginseng from ginsengs of other countries.

A Korean ginseng seedling, when it sprouts, has two cotyledons (primary leaves). Between these cotyledons a small stem supports three tiny leaves. Leaves of the ginseng plants are palmately compound with a little longer petiole whorled on the tip of the stem. The number of leaves varies with the age of the plants and cultivation factors. It is usually related to the age of the plants, i.e., one for yearlings, two for two-year old plants, three for three-year old plants, and so on. Each compound leaf has three to five leaflets. Yearlings have three leaflets, and the older than two-year plants have five leaflets in each compound leaf.

Ginseng is a semi-shade plant and the aerial part above ground is fairly weak. Therefore, if it is exposed to direct sunlight, chlorophyll in the leaves is destroyed, leaving that part dried up and dead. For that reason, it is good to set up a shade of sorts during the high temperatures of summer to create cooler conditions. Moreover, ginseng's growth is very slow as compared to common plants and its fertilizer tolerance is very weak, so when chemical fertilizers are used they often hinder the growth of the plants. Therefore, nutrition management should focus on improving soil with decomposed leaves. Another consideration is ginseng's severe unsuitability for consecutive planting-thus it is desirable to wait usually 10 to 15 years before planting the same field with ginseng again. Reasons to explain this include blight and damage from harmful insects, the lack of particular components in the soil, and the accumulation of toxic components. At present the most likely theory involves blight and insects.

    Given that ginseng has various botanical characteristics which demand great care, high production cost, and hard labor in its cultivation, it is understandable that the end-product is expensive.

 

1. Related Species
   

   
    

   The genus Panax was established by Linnaeus. Depending on who is doing the
   

taxonomy, there are anywhere from six to eight species of the Panax genus (Hiroshi et

al., 1970).

The six species about which there is little debate are as follows:

j
Panax ginseng C. A. Meyer

Panax ginseng C. A. Meyer was found in Korea, North China, Manchuria, Siberia,

and Japan, and usually referred to as Korean or Asian ginseng. Panax ginseng is a long-peduncled plant, with the peduncle 3 to 6 times longer than the petiole. The chromosome number of P. ginseng is 2n=48.

k
Panax quinquefolium L.

Panax quinquefolium L. was found in America and Canada, and commonly called American ginseng, Canadian ginseng, or North American ginseng. This species is a short-peduncled plant. Its flowering pedunclees are equal to, shorter than, or only slightly exceeding the petioles of the same plant. The chromosome number of P. quinquefolium is 2n=48.

l
Panax trifolium L.

Panax trifolium L. was found in North America, and commonly called dwarf ginseng or ground nut. The plants of Panax trifolium L. are all sexually specialized (Hu, 1976). The male plants bear white flowers with slender long pedicels 5 or 6 times longer than the obconic floal tube. The female plants bear pink flowers with short strout pedicels.

m
Panax japonicum C. A. Meyer

Panax japonicum C. A. Meyer was found in only in Japan, and called Japanese ginseng or Chikusetsuninjien. This species is a long-peduncled plant.

n
Panax notoginseng Burkill

Panax notoginseng Burkill was found in China, and commonly called San Chi or Tien Chi ginseng.

o
Panax pseudoginseng Wallich

Panax pseudoginseng Wallich was found in India, Nepal, Bhutan and Sikkim (Wallich, 1829).

 

Of these six ginseng species, Panax ginseng C. A. Meyer and Panax quinquefolium L. are thought to have exceptional curative properties and therefore have the greatest commercial value.

 

1. Distribution and Cultivation
   

   
    

   Natural ginseng, Panax ginseng C. A. Meyer, is distributed in East Asia of 30-48
   

north latitude such as Korea, the northeast of China, and the Russian Far East because it enjoys the cooler climate conditions of the temperate zone.

Ginseng grows all over Korea of 33 to 46 north latitude, especially in the Tae-Baek

mountain range and the northern district of Korea. And it is distributed in a range of 100-800 m above sea level (Fig. 3). Natural ginseng, that is, wild ginseng, has been disappearing gradually while its demand for medicinal use, trade, and political exchange, have all increased. Therefore, people began cultivating it artificially. The early methods of artificial cultivation involved sowing the seeds of planting the seedlings of wild ginseng in the forest; then it was later moved gradually from mountainous to flat areas, and eventually to today's shaded cultivation method. At present, ginseng cultivation prevails throughout almost all of Korea.

The environmental conditions suitable for Korean ginseng cultivation include an

average temperature of 0.9°C to 13.8°C, and summer average of 20°C to 25°C. Rainfall should average 1,200 mm annually, with comparatively little snow. Direct sunlight is harmful, diffused light being preferred in amounts 1/8 to 1/13 of the total sunlight capacity. Sandy loam is good for surface soil, but for subsoil it is desirable to have somewhat more clay. Old soil neither too fertile nor damaged by blight or insects, and with a pH of 5.5 to 6.0, is very suitable.

It is extremely difficult to adapt and raise ginseng in places where climate or soil is incompatible with its natural surroundings. Even if it is possible to cultivate, it is recognized that ginseng unsuitably grown differs in shape, quality, and pharmacological effect.

 

1. Biotechnological Approaches for Micropropagation and Production of Active Principle
   

   
    

1. Micropropagation
   

   
    

   Korean ginseng plants (Panax ginseng C. A. Meyer) are perennial herbaceous plant,
   

which grow very slowly. Cultivation of ginseng plants requires a period of more than three years to produce seeds. At time of seed harvest, zygotic embryos of Korean ginseng are still in a immature globular stage, thus the seeds require stratification and cold treatment for several months. Therefore, tissue culture procedures could contribute to clonal propagation and genetic breeding in ginseng. However, it has been accepted that plant regeneration from somatic embryos of ginseng was a very recalcitrant. In many reports of Korean ginseng tissue cultures, structurally abnormal somatic embryos such as multicotyledonary or multiple embryos frequently formed (Arya et al., 1991; Butenko et al., 1968; Chang et al., 1980; Lee et al., 1990). In addition, regenerated plantlets from somatic embryos developed into multiple shoots without or inadequate roots (Chang et al., 1980; Choi et al., 1998; Shoyama et al., 1988). Root development of plants is important for the field habituation after transfer. However, little is known what is the main problem of plant regeneration in ginseng.

In general, exogenous growth regulators are the most important components for somatic embryo induction. In Panax ginseng, many papers concerning somatic embryogenesis were conducted from the callus culture. Lately, direct somatic embryogenesis of ginseng on hormone-free medium can be applied to a technique for plant regeneration (Choi et al., 1994; 1997). This method has some advantages due to the rapid propagation and to the low frequency of genetic variation compared to calli-derived embryogenesis. Choi et al. (1997, 1998) tried to introduce an efficient plant regeneration protocol using direct somatic embryogenesis on hormone-free medium.

When the cotyledon explants were cultured on MS agar medium with 5% sucrose, somatic embryos were developed directly near the basal excised region of cotyledon explants (Figs. 4 and 5). The frequency of somatic embryo formation was the highest (93%) in the cotyledon explants from midmature zygotic embryos and the competence for embryo formation decreased to 66% as the zygotic embryos matured and no embryos formed at seedling stage (60 mm in length) (Table 1). Somatic embryos were developed into multiple or single state (Table 1). The frequency of multiple and single embryo formation differed markedly according to the degree of maturity of the zygotic embryos. On cotyledons from midmature zygotic embryos, most of somatic embryos (96% of total embryos) developed as multiple state, while on cotyledon explants from mature one, 13% of somatic embryos developed into single state (Table 1). In midmature cotyledons, multiple embryos (Fig. 4A, B, D, E) formed on the basal portion of cotyledons, which developed into numerous multiple shoots (Fig. 4B, C, E, F). On a while, in fully mature cotyledons, single embryos formed from single epidermal cells of cotyledons and eventually developed into single cotyledonary embryos (Fig. 5A-C).

It was reported that single and multiple cell origin of somatic embryo depended on the differentiated state of maternal ginseng cotyledon (Choi et al., 1994). We compared the developmental pattern and plant conversion rate of multiple and single embryos. In the culture of immature cotyledons, somatic embryos derived from multiple cells developed into abnormal multiple embryos fused each other and fused to maternal explants, and these embryos regenerated into only multiple shoots (Fig. 4A-F). While, in cotyledons from fully matured zygotic embryos, somatic embryos were originated from single cells and developed into single independent state (Fig. 5A-C). These single embryos developed into normal plantlets with both shoots and roots (Fig. 5D, E). Therefore, direct single embryogenesis derived from single cells is important for normal plant regeneration in ginseng. However, to induce single embryos, only cotyledons from fully matured zygotic embryos should be sampled as explants.

In conclusion mass production of ginseng plants was accomplished via direct single somatic embryogenesis from preplasmolysed ginseng cotyledons, and this protocol may be applied to the micro propagation of Korean ginseng plants.

 

1. Production of Ginsenosides by In Vitro Culture of Ginseng Cells
   

   
    

   In general, ginseng cultivation work requires large facilities and manpower as well as
   

unusually long cultivation times. Therefore, the production of ginsenosides by in vitro culture of ginseng cells or tissues has been studied by a number of investigators (Kim et al., 1980; Choi et al., 1990). Large-scale plant cell cultures may be cost-effective and enable one to produce a higher amounts of ginsenosides. The production of ginsenosides and other secondary metabolites from cell and tissue cultures of Panax ginseng cell lines have been patented by this laboratory (Korea Patent No. 045232, 045233, 045234 and 047779). For ginsenoside production from ginseng cell cultures to be commercially available, significant amounts of ginsenosides must be produced in a relatively short period of time. This can be accomplished with a slowly-growing cell line that produces relatively large amounts of ginsenosides or with a rapidly-growing cell line that produces relatively small amounts of ginsenosides. The ideal, of course, is to select a rapidly-growing cell that produces large amounts of ginsenosides.

    Choi et al. (1994) studied effects of auxins on the ginsenoside-biosynthesis in ginseng cells cultured in liquid media. There have been numerous reports on the conditions of phytohormones to enhance the yields of secondary metabolites, but it is obvious that there is no general rule in most cases of plant cell cultures. The critical factors of secondary metabolite formation is the phytohormone regime. Since 2, 4-D and IAA was clarified as the good phytohormone for the growth of ginseng cells cultured in the liquid medium, experiments were done in 10^-4M of IAA and 3mg/l of 2, 4-D in order to clarify the effects of IAA and 2, 4-D on the ginsenoside biosynthesis in ginseng cells suspension-cultured.

    The amounts of total ginsenoside of KGC2 cultured in 10^-4M of IAA and 3mg/l of 2, 4-D were 12.29 mg and 6.51 mg per g dry weight, respectively. In general, ginseng cells were grown faster in 2, 4-D than in IAA. However, the total ginsenoside was more highly synthesized in 10^-4M of IAA than in 3mg/l of 2, 4-D. Also, amounts of ginsenoside fractions in 10^-4M of IAA were higher than those in 3mg/l of 2, 4-D. Specifically, amounts of ginsenosides Rb₂ and Re in 10^-4M of IAA were increased to 2.3 and 3.2 fold of 3mg/l 2, 4-D. However, the amount of ginsenoside Rg₁ in 3mg/l of 2, 4-D was increased to 2.2 fold of 10^-4M IAA. Choi et al. (1994) investigated the growth of ginseng cells, ginsenoside content and ginsenoside productivity in ginseng cell lines cultured on the MS liquid medium containing 10^-4M of IAA for 34 days. Table 2 shows the growth and amounts of total ginsenoside and ginsenoside productivity of ginseng cell lines at 34 days after culture. In general, the ginsenoside amount was maximized at 34 days after the liquid culture. Especially, KGC 13 was selected as a cell line having the highest total ginsenoside, 65.92 mg per g dry weight, among the other cell lines, such as KGC 2, KGC 15 and KGC 16. The fresh weight of KGC 13 was 1.22g per 15 ml culture solution. Although KGC 13 produced the highest amount of total ginsenoside, KGC 13 was slowly grown in the liquid medium. The amount of total ginsenoside in KGC 15 was 22.45 mg per g dry weight. However, KGC 15, of which the fresh weight was 3.18g per 15ml culture solution, was the most rapidly grown among the other cell lines. In general, the productivity of ginsenoside in the cells is dependent on the capability of the ginsenoside biosynthesis and the growth of individual cells. In this experiment, the productivities of total ginsenoside in KGC 2, KGC 13, KGC 15 and KGC 16 were 12.69mg, 80.42mg, 71.39mg, and 56.04mg per 15ml culture solution, respectively.

    In conclusion, Choi et al. (1994) selected two ginseng cell lines, KGC 13 and KGC 15, having higher productivity of total ginsenoside. In particular, the amount of total ginsenoside in KGC 13 cell line in vitro cultured was the highest reported so far, for any ginseng tissues and was much higher than that in 6 year-old native root. KGC 15 cell line was the most rapidly grown among ginseng cell lines selected. Therefore, the ability of ginseng to produce a medicinal compound by cultured cell line is apparently higher than that of intact plants.

 

1. Chemistry
   

   
    

1. Active Components
   

   
    

2. Ginsenoside (Ginseng Saponin)
   

   
    

   Chemical studies of ginseng components were first reported by Garriques (1854) of
   

the United States, who isolated a blend of amorphous glycoside, called it "panaquilon", and claimed it as a peculiar component of ginseng. And studies of ginseng were restimulated when Brekhman (1957) published a monograph named Panax ginseng suggesting saponin as the active principle contained in ginseng. He found that ginseng exhibits antifatigue effects, increases work efficiency, and can either stimulate or pacify the central nervous system.

In 1960's, Shibata et al. (1963, 1965) isolated 13 kinds of saponins from Korean

ginseng and identified their structures, differentiating them as to their order of moved distance on thin-layer chromatography, ginsenoside Ro, Ra, Rb, Rc, Rd, Re, Rf, Rg, and Rh₁.

Plant saponin gets its name from the fact that it forms a soapy foam when dissolved

in water. In general, it is any of a group of glycosides and forms a rather highly polarized compound which has a destructive effect on red blood cells and a toxicity to fish. In addition, it is able to join with cholesterol in the blood to form a complex. Given this, what is so different about ginseng saponin when compared to that in other plants that makes it effective while not causing the toxic effects which may lead to such problems as hemolysis?

    First, ginseng saponin is a glycoside structured with dammarane from triterpenoid. However, this is not the case in general herbal pharmaceutical saponin. Secondly, while the saponin originating from other plants has polarity with such effects as hemolysis, ginseng saponin is a neutral glycoside which has hardly any toxicity. Thirdly, ginseng saponin's pharmacological action is remarkably different from other herbal medicinal saponins.

    Hydrolysis of glycoside mixtures with acid results in the formation of carbohydrates and their aglycones. Panaxadiol, panaxatriol, b-sitosterol and oleanolic acid are known to be aglycones of ginseng glycosides. Glycosides of panaxadiol and panaxatriol are distributed in ginseng and related plants only, and their physiological activities have attracted much academic interest since it had essentially the same effects as in public experience.

    Glycoside groups containing protopanaxadiol or protopanaxatiol as genuine aglycone are called dammarane triterpene glycoside. First of all, terpenes are carbons whose number is a multiple of 5, that is, 5n (n=2), and in the view of herbal synthesis it is the "n" number of isoprene or isopentane; [CH₂ =CH-C(CH₃)=CH₂]. Therpene is classified according to the number of carbons, and when n=6, triterpene is indicated with 30 carbons. The basic structure of dammarendiol, with its four rings, is dammarane.

    As shown in Fig. 6, what is combined in the position of R₁, R₂, and R₃, in

dammarane's basic structure determines the kind of ginsenoside.

    Ginseng saponin is thus called "ginsenoside", which is a combination of the words ginseng and glycoside. It is known that Korean ginseng, Panax ginseng C. A. Meyer, contains more than 20 kinds of ginsenosides, but as shown in Table 3, only half this number is found in related species. Considering that each of these ginsenosides has different pharmacological actions, it becomes apparent that Korean ginseng, Panax ginseng C. A. Meyer, might have a pharmacological effectiveness superior to any other.

 

1. Other Active Components
   

   
    

   There are other very important substances in ginseng. Among them are components
   

that demonstrate anticancer, antioxidation, antidiabetes, and anti-inflammation effects, as well as those which exhibit hematopoiesis.

Polyacetylene compounds (Ahn et al., 1988; Kim et al., 1989) exhibit an anticancer effect, and phenol compounds (Han et al., 1981, 1992) exhibit antioxidation and, thus, anti-aging effects through the inhibition of the formation of lipid peroxide in the body.

Among refined oil constituents, there appear pinene, which acts as an analgesic, and ocinene, which has an antiphlogistic effect, antibiotic tendency, and also inhibits overfermentation in the intestinal tract. Moreover, through the discovery of antidiabetic constituents such as adenosine, acidic peptide, and a manganese-containing substance, and the discovery of other non-saponin constituents which have effective pharmacological action, the importance of these non-saponin ingredients was recognized (Han et al., 1981; Okuda, 1990). Meanwhile, the importance of the anti-inflammatory constituents, panaxynol and linoleic acid, was emphasized. In addition, 12 to 16% of nitrogen-containing compounds such as protein, nucleic acid, as well as many other components including essential amino acids, essential fatty acids are contained in Korean ginseng (Panax ginseng C. A. Meyer). Therefore, Korean ginseng is spotlighted not only for pharmacological use, but also as a health food.

 

1. Pharmacological Properties
   

   
    

2. Effects of Ginseng on Hepatic Diseases
   

   
    

   When ginseng was administered to rats who had been given a two-thirds partial
   

hepatectomy, the rate of liver regeneration was higher by 34% than that in the control (Igarashi et al., 1975). Liver disease is usually hepatitis, especially acute viral hepatitis type B, and when this becomes chronic it becomes cirrhosis of the liver, and may progress further to liver cancer. Therefore, the treatment of hepatitis is most important to prevent it from passing into a chronic state. Professor Koo (1981) observed that ginseng given to 201 patients of acute viral hepatitis-B, not only promotes early recovery but also prevents the disease from becoming chronic. Ginseng reduces tissue damage such as the death of liver cells induced by acutely toxic chemicals such as carbon tetrachloride or phenacetin (Hahn, 1978). Moreover, the fact that ginseng promotes RNA synthesis in the liver was revealed (Igarashi et al., 1975).

    Many people have heard that ginseng is good for a hangover, and probably many have experienced this themselves. Joo et al. (1984) studied the effect of ginseng saponin fraction on enzymes involved in alcohol metabolism such as alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS). Electron micrographs of the liver from rats receiving 12% ethanol and 12% ethanol supplemented with ginseng saponin were also compared. A moderate amount of ginseng saponin fraction stimulated ADH, ALDH and MEOS in vivo as well as in vitro. It appears that ginseng saponin fraction enhances the removal from the liver of the toxic aldehyde produced during ethanol oxidation. Furthermore, in the presence of saponin fraction, the excess hydrogen generated from the oxidation of ethanol is efficiently mobilized for biosynthetic processes and thus protects the liver against alcohol intoxication. Electron microscopic observation revealed that the hepatocytes of rats treated with 12% ethanol for 6 days were severely damaged, whereas no damage was observed in hepatocytes of ginseng saponin-treated animals. Such results suggest that the ginseng fraction protects the liver against ethanol intoxication. Yu et al. (1982) measured the activity of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP) in serum to study the effect of ginseng on alcohol-intoxication. Alcohol administration induced fat degeneration, the accumulation of intracellular lipid, the thickening of venular wall, cellular swelling, congestion and bile pigmentation in the Kuffer cell and also increased the GOT, GPT, and ALP activities. Combined treatment with ginseng saponin and a moderate amount of ethanol, however, did not induce any histological changes and furthermore, the levels of GOT, GPT and ALP were lower than the control group receiving alcohol treatment alone.

 

1. Effects of Ginseng on Diabetes Mellitus
   

   
    

   Chinese medicine has known that ginseng increases stamina, prevents collapse,
   

increases the secretions of body fluids, and quenches thirst. This means that ginseng can counter the special characteristics of diabetes, such as thirst and body weakness. And recent research reports reveal ginseng's effect on the treatment of diabetes as well as its prevention. Ginseng not only acts directly to lower the level of blood sugar, but also acts indirectly and improves the symptoms that accompany diabetes and its complications. Okuda (1978), Ando et al. (1979, 1980) and Sekiya et al. (1981) isolated insulin-like compounds from water extracts of Korean ginseng and identified them as acidic peptides, ginsenoside-Rb₁ and Re, adenosine and Mn-containing compounds. Recently, it was found that ginsenoside Rb₂, which is one of the components of ginseng saponin, also exhibits the effect of lowering blood sugar levels. Meanwhile, Professor Kimura (1980, 1981) reported that he had isolated DPG3-2, which is a blood sugar depressive component and found that this component has the function of stimulating insulin release.

 

1. Anticarcinogenic Effects of Ginseng
   

   
    

   Effects to develop the use to cancer chemotherapy have intensified over the last
   

several decades, however, many cancers remain difficult to cure. It seems that the 20^th century is destined to end with the war against cancer far from win. The studies of Dr. Yun (1997) have focused on the anticarcinogenicity of Panax ginseng C. A. Meyer, known as mysterious tonic, against various chemical carcinogens since 1978. The prolonged administration of red ginseng extract inhibited the incidence and also proliferation of pulmonary tumors induced by DMBA, urethane and aflatoxin by modified long term in vivo experiments. A 9 weeks medium-term anticarcinogenicity test using pulmonary adenoma induced by benzo(a)pyrene was established. Statistically significant anticarcinogenic effects were observed in powder and extract of 6-year fresh ginseng, 5- and 6-year white ginseng, and 4-, 5- and 6-year red ginseng. Comparative studies on anticarcinogenicity between Panax ginseng C. A. Meyer and Panax notoginseng using the 9 weeks medium-term mouse system (Yun's test) were carried out. In Panax ginseng, both the water extract ad the ethanol soluble fraction showed significant reduction of lung tumor incidence compared to benzo(a)pyrene alone group. However, in the case of Panax notoginseng, only the highest dose of ethanol soluble fraction showed anticarcinogenicity. The ethanol insoluble fractions of both ginsengs did not show any significant decreases of lung adenoma incidence.

    An epidemiological study to confirm whether ginseng has anticarcinogenic effect in human being was conducted in relation to two case-control studies on patients and a cohort study on a population of a ginseng cultivation area. In case-control studies, odd ratios of the cancer of lip, oral cavity and pharynx, larynx, lung, esophagus, stomach, liver, pancreas, ovary and colorectum were significantly reduced. In a cohort study with seven years follow-up conducted in a ginseng cultivation area, ginseng intakers had a decreased relative risk (RR: 0.38) compared with non-intakers. On the types of ginseng, the RRs of cancer were 0.52 for fresh ginseng extract intakers and 0.47 for multiple combination intakers. Among 24 red ginseng intakers, there were no cancer deaths. The RRs of ginseng intakers were 0.35 in gastric cancer and 0.23 in lung cancer. There was a decrease in risk with rising frequency of ginseng consumed, showing a statistically significant dose-response relationship. These findings strongly suggest that Panax ginseng C. A. Meyer has non-organ specific cancer preventive effect against various cancers. In 1984, potential cytotoxic activity of the petroleum ether extract of Panax ginseng root (crude GX) and its partially purified fraction (7:3 GX) on tumor cells were compared with that of 5-fluorouracil (5-FU). Administration of crude GX normalized the elevated level of white blood cells in mice caused by inoculation with S-180 cells. A decrease in Hb value in rats inoculated with Walker 256 was also restored to the normal level by GX-treatment. Administration of the 7:3 GX fraction increased the survival time of the mice challenged with S-180 cells by 1.5 to 2 times that of the control group. These results demonstrate that the inhibitory effects of ginseng on the proliferation of cancer cells are attributed to the lipid-soluble fraction of ginseng.

 

1. Effects of Ginseng on the Cardiovascular System
   

   
    

   Ginsenosides reduced the mean arterial blood pressure in anesthetized rats. The
   

studies of Kim (1999) have focused on characterizing the endothelium-dependent and independent relaxation elicited by ginsenosides, a mixture of saponin extracted from Panax ginseng, in isolated rat aorta. Ginsenosides stimulated the formation of nitric oxide (NO) in endothelial cells which caused relaxation of blood vessels by enhancing the production of cyclic GMP in rings of rat and rabbit aorta and dog femoral and coronary artery. Ginsenosides increased the permeability of the vascular smooth muscle cell membrane to K⁺, resulting in hyperpolarization, which indirectly relaxed the blood vessel by decreasing the opening of voltage-dependent Ca²⁺ channels.

Ginsenoside Rg₃ was the most potent vasodilator among the ginsenosides examined.

These results indicated that ginsenosides-inducced relaxation might be regulated by dual mechanisms. Ginsenosides-induced relaxation in rat aorta was caused by release of endothelium-derived nitric oxide and direct inhibition of vascular smooth muscle via the activation of K⁺ channels. Endothelium-dependent relaxation to acetylcholine was impaired in the thoracic aorta isolated from hypercholesterolemic rabbits. Dietary supplementation of rabbits with ginsenosides improved the endothelium-dependent relaxation to acetylcholine in the aortic blood vessels in cholesterol-fed rabbits, providing evidence that ginsenosides increased production of nitric oxide by endothelial cells. Ginsenosides reduced the blood pressure of spontaneous hypertensive rats (SHRs). Acetylcholine caused endothelium-dependent contraction in the aorta of SHRs. Ginsenosides prevented endothelium-dependent contaction to acetylcholine in the isolated thoracic aorta of SHR. Prostaglandin endoperoxide (PGH2)- and oxygen-derived free radcal-induced contractions of the isolated aorta of SHR were significantly inhibited by ginsenosides. These results indicate that hypotensive effect of ginsenosides in SHR may be associated with decreased formation of PGH2 and inhibition of superoxide anion in the aorta. Ginsenosides reduced rat and human platelet aggregation induced by collagen or thrombin, possibly by inhibiting the formation of TXA2. These results indicate that ginsenosides may be useful in endothelium-dependent relaxation, vasorelationa via activation of potassium channels, hypertension, platelet aggregation, atherosclerosis, and the positive inotropic effect.

 

1. Antifatigue, Antistress and Anti-Aging Effects of Ginseng
   

 

The ginsenoside Rg₁ exerted an antifatigue effect in mice subjected to exhaustive

exercise (Saito et al., 1974). Takagi (1974) conducted pharmacological studies of active components extracted from ginseng. Water extracts, Rg₁ and the G-5 fraction exhibited antifatigue effects. When seven ginsenosides, Rb₁, Rb₂, Rc, Rd, Re, Rf, and Rg₁, were individually administered to mice, they all showed antifatigue effects (Kaku et al., 1975).

    Brekhman (1969) studied the pharmacological effect of ginseng and presented the concept of ginseng's tonic effect as a phenomenon that generally increases resistance, and said that ginseng improves defense ability nonspecifically by increasing resistance against harmful environmental conditions in the body. This effect of ginseng was named "adaptogen effect". Dr. Petkov (1978) found that Korean ginseng accelerates the release of hormones related to the defense system against stress and thus exhibits an anti-stress effect. The effects of ginsenosides (Rb₁, Rb₂, Rc, Re, and Rg₁) isolated from Panax ginseng and their partial hydrolyzates, prosapogenins, on specific cold stress (SART) and water immersion stress in mice were studied (Kita et al., 1981). A single intraperitoneal administration of ginsenosides or prosapogenins did not affect the pentobarbital-induced sleeping time in non-stressed mice. But the inhibition of normal body weight increase in stressed mice was significantly prevented by the administration of ginsenosides and prosapogenins for 5 days at a dose of 2.5mg/kg body weight. Writhing, caused by the administration of acetic acid, was significantly inhibited by ginsenosides and prosapogenins in non-stressesd and SART-stressed mice. Studies on the effect of red ginseng powder and extract on the sex cycle of the adult IV-CS strain female mice exposed to chronic hanging stress were conducted by Bao et al. (1984). Administration of red ginseng powder and extract prevented disturbances on the sex cycle and a decrease in body temperature induced by chronic stress.

    The non-saponin fraction of ginseng inhibited the harmful action of oxygen radicals such as O₂^- , H₂O₂^- , OH^- , ¹O₂ and thus prevented tissue degeneration which causes aging (Park et al., 1984). The mechanism of the antioxidant effect of ginseng was also investigated. The non-saponin fraction of ginseng prevented the inhibition of skin collagen gelation induced by xanthine and xanthine oxidase. Total ginseng extract and its non-saponin fraction exhibited a quenching effect on ¹O₂. These results suggest that the collagen alteration induced by oxygen radicals was prevented by the active components present in the non-saponin fraction which have a free radical (¹O₂) quenching property. Also, Cho et al. (1984) investigated the effect of ginseng on age-related enzymes such as isocitrate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, glutachione peroxidase, and glutathione reductase. Ginseng extract enhanced the activities of those age-related enzymes in vitro and also retarded a decline in their activity occurring in relation to aging. Such results indicate that ginseng has the potential to retard aging processes.

 

1. References
   

 

1. Ahn, B.Z., Kim, S.I., Kang, K.S., and Kim, Y.S. 1988. The action of cytotoxic components of Korean ginseng against L1210 cells and their structure-activity relationship. Proc. 5^th Int'l Ginseng Symp., Korea Ginseng and Tobacco Research Institute, Korea: 19-24.
   
2. Ando, T., Muraoka, T., Yamasaki, N. and Okuda, H. 1979. Preparation of insulin-like peptides from Panax ginseng. Proc. Symp. Wakan Yaku 12:15.
   
3. Ando, T., Muraoka., T., Okuda, H. and Yamasaki, N. 1980. Preparation of an antilipolytic substance from Panax ginseng. Planta Medica 38:18.
   
4. Arya, S., Liu, J.R., Eriksson, T. 1991. Plant regeneration from protoplasts of Panax ginseng (C. A. Meyer) through somatic embryogenesis. Plant Cell Rep. 10:227-281.
   
5. Bao, T.T. and Saito, H. 1984. The effects of red ginseng, vitamins and their preparations (IV): Effects on the sex cycle in stressed female mice. Japanese Pharmacology & Therapeutics 12(4):37.
   
6. Bittles, A.H., Fulder, S.J., Grant, E.C., and Nichills, M.R. 1979. The effect of ginseng on lifespan and stress response in mice. Gerontology 25:125.
   
7. Brekhman, I.I. and Dardymov I.V. 1969. New substances of plant origin which increase non-specific resistance. Ann. Rev. Pharmacol. 9:419-430.
   
8. Butenko, R.G., Brushwitzky, I.V., Slepyan, L.I. 1968. Organogenesis and somatic embryogenesis in the tissue culture of Panax ginseng C. A. Meyer. Bot. Zh. 7: 906-913.
   
9. Chang, W.C., Hsing, Y.I. 1980. Plant regeneration through somatic embryogenesis in root-derived callus of ginseng (Panax ginseng C. A. Meyer). Theor. Appl. Genet. 57:133-135.
   
10. Cho, Y.D., Koo, B.S. and Lee, S.J. 1984. Studies of ginseng extract on age-related enzymes. Proc. 4^th Int'l Ginseng Symp.: 37.
    
11. Choi, K.T., Park, J.C. and Ahn, I.O. 1990. Saponin production in tissue culture of ginseng (Panax ginseng C. A. Meyer). Korean J. Ginseng Sci. 14:107-111.
    
12. Choi, K.T., Lee, C.H., Ahn, I.O., Lee, J.H. and Park, J.C. 1994. Characteristics of the growth and ginsenosides in the suspension-cultured cells of Korean ginseng (Panax ginseng C. A. Meyer). Proc. Int'l Ginseng Conference, Vancouver: 259-268.
    
13. Choi. Y.E., Sho, W.Y. 1994. Origin of somatic embryos induced form cotyledons of zygotic embryos at various developmental stages of ginseng. J. Plant Biol. 37: 365-370.
    
14. Choi. Y.E., Yang, D.C., Kim, H.S., Chio, K.T. 1997. Distribution and changes of reserve materials in cotyledon cells of Panax ginseng related to direct somatic embryogenesis and germination. Plant Cell Rep. 16: 841-846.
    
15. Choi, Y.E., Yang, D.C., Park, J.C., Soh, W.Y., Choi, K.T. 1998. Regenerative ability of somatic single and multiple embryos from cotyledons of Korean ginseng on hormone-free medium. Plant Cell Rep. 17: 544-551.
    
16. Hahn, D.R. 1978. Pharmaco-biological action of the ginsenosides Rb1, Rg1, and Re. Proc. 2^nd Int'l. Ginseng Symp.: 135.
    
17. Han, B.H., Park, M.H. and Han, Y.N. 1981. Studies on the antioxidant components of Korean ginseng (III). Identification of phenolic acid. Arch. Pharm. Res. 4(1): 53-58.
    
18. Han, B.H., Park, M.H., Han, Y.N., and Suh, D.Y. 1992. Chemical and biochemical study on non-saponin constituents of Korean ginseng. Korean J. Ginseng Sci. 16(3): 228-234.
    
19. Hwang, W.I. and Oh, S.K. 1984. Study on the anticancer activities of lipid soluble ginseng extract and ginseng saponin derivatives against some cancer cells. Korean J. Ginseng Sci. 8(2): 153.
    
20. Igarashi, S., Oka, Y., Oda, T. and Oura, H. 1975. Effect of saponin extract from Panax ginseng on protein and amino acid metabolism in liver. Proc. Symp., Waken Yaku 9:63.
    
21. Joo, C.N. 1984. The preventive effect of the saponin fraction of Panax ginseng C.A. Meyer against ethanol intoxication of rat liver. Proc. 4^th Int'l. Ginseng Symp.: 63.
    
22. Kaku, T., Miyata, T., Uruno, T., Sako, I. and Kinoshita, A. 1975. Chemico-pharmacological studies on saponins of Panax ginseng C.A. Meyer. Arzenim-Forsch. (Drug Res.) 25(4): 539.
    
23. Kim, M.W., Choi, K.T., Bae, H.W. and Kang, Y.H. 1980. Effect of 2, 4-D and kinetin on saponin content of callus derived from ginseng root. Korean J. Botany 23: 91-98.
    
24. Kim, N.D. 1999. Cardiovascular actions of ginsenosides. Proceedings of '99 Korea-Japan Ginseng Symposium: 1-15.
    
25. Kim, S.I., Lee, Y.H., and Kang, K.S. 1989. 10-Aceylpanaxytriol, a new cytotoxic polyacetylene from Panax ginseng. Yakhak Hoeji 33:118.
    
26. Kimura, M. 1980. Hypoglycemic components in ginseng radix and its insulin Release. Proc. 3^rd Int'l Ginseng Symp.: 37.
    
27. Kimura, M., Waki, I., Tanaka, O., Nagai, Y. and Shibata, S. 1981. Pharmacological sequential trials for the fractionation of components with hypoglycemic activity, in alloxan diabetic mice, from ginseng radix. J. Pharm. Dyn. 4: 402.
    
28. Kita, T., Hata, T., Kawashima, Y., Kaku, T., and Itoh, E. 1981. Pharmacological actions of ginseng saponin in stress-mice. J. Pharm. Dyn. 4: 387.
    
29. Koo, K.H. 1981. Clinical observation on the preventive effect on Panax ginseng against liver cirrhosis and its treatment at an early stage. Ann. Rept. Korean Ginseng Res., Korea Ginseng & Tobacco Research Institute.
    
30. Lee, H.S., Liu, J.R., Yang, S.G., Lee, Y.H., Lee, K.W. 1990. In Vitro flowering of plantlets regenerated from zygotic embryo-derived somatic embryos of ginseng. HortSci 25: 1652-1654.
    
31. Okuda, H. 1978. Studies on insulin-like substances in Panax ginseng. Proc. 2^nd Int'l Ginseng Symp.: 75.
    
32. Okuda, H., Lee, S.D. 1990. Biological activities of non-saponin compounds isolated from Korean red ginseng. Proc. Int'l Symp. on Korean ginseng. The Society for Korean Ginseng, Seoul, Korea: 15-19.
    
33. Park, C.W., Lim, J.K., Lee, J.S. and Chung, M.H. 1984. Effects of ginseng components on the actions of oxygen radicals to the gelation of skin collagen. The Seoul J. Med. 25(1):45.
    
34. Petkov, V.D. 1978. Effect of ginseng on the brain biogenic monoamines and 3', 5'-AMP system: Experiments on rat. Arzeim Forsch. 28: 388-393.
    
35. Saito, H., Yoshida, Y. and Takagi, K. 1974. Effect of Panax ginseng root on exhaustive exercise in mice. Japanese J. Pharmacol. 24: 119.
    
36. Sekiya, K. and Okuda, H. 1981. Purification of an anti-lipolytic (insulin-like) substance from Panax ginseng. Proc. Symp. Wakan Yaku 14:133.
    
37. Shibata, S., Fujita, M., Itokawa, H., Tanaka, O., and Ishii. T. 1963. Panaxadiol, a sapogenin of ginseng roots (I). Chem. Pharm. Bull. 11:759-761.
    
38. Shibata, S., Tanaka, O., Soma, K., Iita, Y., Ando, T., and Nakamura, H. 1965. Studies on saponins and sapogenins of ginseng. The structure of panaxatriol. Tetrahedron Lett. 3: 207-213.
    
39. Shoyama, Y., Kamura, K., Nisioka, I. 1998. Somatic embryogenesis and clonal multiplication of Panax ginseng. Planta Med. 54:155-156.
    
40. Takagi, K. 1974. Pharmacological studies on ginseng. Proc. 1^st Int'l Ginseng Symp.: 119.
    
41. Wallich, N. 1829. An account of the Nepal ginseng. Trans. Med. Phys. Soc. Calcutta 4:115-120.
    
42. Yu, H.Y., Kim, C.M. and Koo, K.H. 1982. An experimental study on the effect of ginseng saponin upon alcoholic liver injury. J. Hanyang Med. Coll. 2(2): 287.
    
43. Yun, T.K. 1997. Anticarcinogenic and cancer preventive effects of Korean ginseng. Proceedings of '97 Korea-Japan Ginseng Symposium: 1-31.
    
44. Zhao, X.Z. 1990. Antisenility effect of ginseng rhizome saponin. Chung Hsi Chieh Ho Ta Chih 10(10): 486-589.
    
45. Zhuo, D.H. 1982. Preventive geriatrics: An overview from traditional Chinese medicine. American J. Chinese Med. 10(1-4): 32.
    

    
     

    
     

    
     

    
     

    
     

    
     

    
     

FIGURE LEGENDS

 

Fig.1. Ripe red fruits of Korean ginseng.

 

Fig.2. 6-year old roots of Korean ginseng.

 

Fig 3. Korean ginseng field.

 

Fig 4. Multiple shoot formation from somatic multiple embryos of ginseng. A, D; Somatic multiple embryos formed directly from the basal surface of midmature cotyledons on MS basal medium after 1 month of culture (bars: 830 um). B, E; Greening of cotyledonary multiple embryos just after treatment with 3´10^-5M GA₃, for 2 weeks (bars: 2.3 cm). C, F; Multiple shoots formed from somatic multiple embryos on half-strength MS medium (bars: 3.2 cm). Arrows in B and C indicate radical region.

 

Fig. 5. Plant regeneration with both shoots and roots from somatic single embryos of Korean ginseng. A; Somatic embryos formed directly from cotyledons of mature zygotic embryos on MS basal medium after 1 month (bar: 300 mm). B; Cotyledonary embryos after 2 months (bar: 920 mm). C: Somatic single embryos with well-developed cotyledons and radicles after separation from the cotyledon explants (bar: 1.2 cm). D; Germinating somatic single embryos with well-developed roots on MS medium with 3´10^-5M GA₃ (bar: 2.2 cm). E; Plantlets regenerated from single embryos on half-strength MS basal medium with both shoots and roots (arrows roots, arrowheads shoots, bar: 1.36 cm).

 

Fig. 6. Structure of ginsenosides

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Fig. 1

 

 

Fig. 2

 

 

Fig. 3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Fig. 4

 

 

 

 

 

 

 

Fig. 5

 

 

Fig. 6

 

 

 

 

 

 

Table 1. Frequency of somatic multiple or single embryo formation from cotyledon explants of Korean ginseng zygotic embryos at different stages of maturity on hormone-free MS medium after 2 months of culture

 

Stage of Size Explants forming Proportion of embryos Explant (mm) Somatic Embryos (%) Multiple Single

Immature 1 0 0 0 Cotyledon 3 94±7 96 4 Midmature Cotyledon 6 66±5 13 87 Mature Cotyledon 60 0 0 0 Seedling

 

Table 2. Fresh weight and ginsenoside content of ginseng cell lines cultured in the liquid medium containing 10^-4M of IAA for 34 days

 

Cell lines FW Ginsenoside Productivity (g/15ml) (mg/g dry weight) (mg/15ml media)

KGC 2 1.03 12.32 12.69 KGC 13 1.22 65.92 80.42 KGC 15 3.18 22.45 71.39 KGC 16 1.85 30.29 56.04

Initial inoclum size=200mg

Productivity=Amount of cells (g/15ml of culture media) X total ginsenoside (mg/g dry weight)

 

Table 3. The composition of ginsenosides in Korean ginseng (Panax ginseng C.A. Meyer), American ginseng (Panax quinquefolium L.), and Chinese Tienchi ginseng (Panax notoginseng Burkill)

 

Components P. ginseng P. quinquefolium P. notoginseng

Total number of 22 13 14 Ginsenosides Panaxadiol group 14 8 5 Panaxadiol group 7 4 9 Oleanolic acid group 1 1 0