The use of herbals has increased considerably while their efficacy and safety remain untested. This unsupported surge in demand has prompted a call for their clinical evaluation. One area in which evaluations are emerging is ginseng and diabetes. Growing evidence is accumulating from in vitro and animal models indicating that various ginseng species, American (Panax quinquefolius L), Asian (Panax ginseng C.A. Meyer), Korean Red, San-chi (Panax notoginseng [Burk.] P.R. Chen), and the non-panax species Siberian (Eleutherococcus senticossus) ginsing, and their fractions, saponins (ginsenosides) and peptidoglycans (panaxans for panax species and eleutehrans for Siberian ginseng), might affect carbohydrate metabolism and related signaling molecules. Recent human studies from our laboratory have also shown a blood glucose lowering effect of American ginseng (AG) and some other ginseng spices postprandially after acute administration and chronically after administration for 8-weeks in people with type 2 diabetes. Although generally encouraging, these data only indicate a need for more evaluations of ginsengs safety and efficacy. Because of poor industry standardization, it is not known whether all ginsengs will affect blood glucose. In this regards some ginseng batches have demonstrated null effects while others have even raised postprandial glycemia. Clinical research should therefore focus on components involved in its glucose lowering effects.

Clinical study on hemodynamics of healthy elders before and after tread mill. Using doubleblind, placebo-controlled study design. Seventy-five 50-70 years old volunteers without organic disease were divided into two groups, Ginseng group and control group. Each subject was received 3 g Korea Red Ginseng (KRG) capsules or placebo per day for 4 weeks. Before and after administration 4 weeks, the symptoms were asked and hemodynamics parameter such as pump function, systolic function, preload and afterload were recorded before and after tread mill 1,5, 10 minutes by the method of thoracic impedance cardiograph. The result showed that Ginseng could improve quality of life, had obvious effect of increasing PEP (pre-ejection period), PEP/LVET (pre-ejection period/left ventricular ejection period), PCWP (wedged pressure pulmonary capillary). The change rate of HR (heart rate), SV (stroke volume) in KRG group were much lowered, while EF (ejection fraction), LVET (left ventricular ejection period), LVEDP (left ventricular end diastolic pressure) was recovered much quickly. The circulation showed Ginseng could improve the quality of life though its promoting circulation function which are increasing both the systolic function and the preload.

Panax ginseng C. A. Meyer has been one of the most highly recognized medicinal herbs in the Orient. Previous experiments have demonstrated that $Rg_3,\;and\;Rg_5$ statistically significantly decreased the incidence of benzo(a)pyrene-induced mouse lung tumor, $Rh_2$ showed tendency of decrease and $Rh_1$ showed no effect. It was, therefore, concluded that $Rg_3,\;Rg_5\;and\;Rh_2$ are active cancer chemopreventive components in red ginseng and they either singularly or synergistically act in the prevention of cancer. This study was undertaken to compare the cancer chemopreventive effects of $Rg_3,\;Rg_5\;and\;Rh_2$(purity: more than $60\%$) isolated from fermented ginseng extract and BST fermented ginseng with fortified ginsenoside $Rg_3\;and\;Rh_2$. The cancer chemopreventive effects were investigated in experimental groups treated with benzo(a)pyrene(BP) with ginsenoside $Rg_3,\;Rg_5\;Rh_2\;or\;BST$ at three doses of $50^{\circ}C/ml,\;100^{\circ}C/ml\;and\;200^{\circ}C/ml$ When mice given with $50^{\circ}C/ml$ concentration of ginsenoside $Rg_3$ combined with BP for 6 weeks after BP administration, $Rg_3\;showed\;60\%$ of lung tumor incidence, where as $100^{\circ}C/ml\;and\;200^{\circ}C/ml\;of\;Rg_3$ combined with BP groups had significant decrease of incidence $(40.0\%)$ respectively, with the inhibition rate being $35.5\%.$ While the tumor incidence was not decreased in the group treated with BP and 50 of $Rg_5,$ the incidence was $34.0\%\;and\;32.0\%$ in the group treated with BP and 100 and 200 of $Rg_5$, respectively. These incidences were significantly less than the group treated with BP alone, with the inhibition rate being $45.2\%\;and\;48.4\%,$ respectively. On the other hand, in the group treated with BP and 50 of ginsenoside $Rh_2,$ the tumor incidence was not decreased. However, the incidence was $40.0\%\;and\;38.8\%$ in the experimental treated with BP and 100 and 200 of $Rh_2,$ respectively, with the inhibition rate being $45.2\%\;and\;48.4\%,$ respectively. In addition, the incidence showed the tendency to decrease in the experimental group treated with BP and 50 of BST which contained $16.2\%\;of\;Rh_2,\;15.4\%\;of\;Rg_3\;and\;2.5%\;of\;Rg_5.$ The tumor incidence was $54.0\%$ in this group. In the group treated with 100 and 200 of EST, the incidence was $34.0\%\;and\;30.0\%,$ respectively, the incidences significantly being lower than the group treated with BP alone, with the inhibiting rate being $45.2\%\;and\;51.6\%,$ respectively. The results of this study strongly suggested that ginsenoside $Rg_3,\;Rg_5\;and\;Rh_2$ are the active components of red ginseng having a cancer chemopreventive activity and $Rg_5$ is the strongest cancer chempopreventive among them. On the other hand, the results demonstrating that the incidence of lung tumor was more markedly reduced by BST fermented ginseng with fortified ginsenoside $Rh_2\;or\;Rg_3$ compared to the single component alone, suggest that the combination of these components may remarkablely improve the cancer preventive effect

Many cultures have traditions that encompass the use of herbs, spices, and other plants for medicinal purposes. From the ancient past to the present medicinal knowledge has been passed down to new generations in the form of shamans, medicine men, healers, and the like. In the past decade there has been a surge of scientific interest in complementary and alternative medicine, much of which has its origins in traditional medicine. It has been recognized for some time that dietary patterns and content affect cancer risk. Epidemiological studies have strongly suggested that the fruit and vegetable content of the diet associates with reduced risk for colon, lung, prostate, and other cancers. Many different types of cellular mechanisms have been postulated by which compounds in botanicals can prevent cancer. Mechanisms particular to the prevention of colon cancer will be addressed in this review.

Ginseng has been used as a key constituent in traditional medicine prescriptions for centuries. Other than its well-known anti-stress and adaptogenic properties, ginseng has also been shown to be very effective in treating age-related deterioration in metabolic and memory functions. Although it is generally believed that the saponin (GS) fraction of the ginseng root accounts for the bioactivity of ginseng, a direct demonstration on which ginsenoside does what is still generally lacking. In the past decade, our laboratory has endeavored to identify the active GS components involved in energy metabolism, memory, and anti-neurotoxicity. To examine the ergogenic effects of GS in enhancing aerobic capacity, rats were subjected to either severe cold ($40^{\circ}C$ under helium-oxygen, two hours) or exercise workload $(70\%\;VO_{2}max,$ to exhaustion). Acute systemic injection (i.p.) of ginseng GS (5-20 mg/kg) significantly elevated both the total and maximum heat production in rats and improved their cold tolerance. However, pretreating the animal with the optimal dose (10 mg/kg) of GS devoid of $Rg_1\;and\;Rb_1$ failed to elicit any beneficial effects in improving cold tolerance. This indicates that either $Rb_1\;and/or\;Rg_1$ may be essential in exemplifying the thermogenic effect of GS. Further studies showed that only pretreating the animals with $Rb_1(2.5-5\;mg/kg),\;but\;not\;Rg_l,$ resulted in an increase in thermogenesis and cold tolerance. In contrast to the acute effect of GS on cold tolerance, enhancement of exercise performance in rats was only observed after chronic treatment (4 days). Further, we were able to demonstrate that both $Rb_1\;and\;Rg_1$ are effective in enhancing aerobic endurance by exercise. To illustrate the beneficial effects of GS in learning and memory, a passive avoidance paradigm (shock prod) was used. Our results indicated that the scopolamineinduced amnesia can be significantly reversed by chronically treating (4 days) the rats with either $Rb_1\;or\;Rg_1$ (1.25 - 2.5 mg/kg). To further examine its underlying mechanisms, the effects of various GS on ${\beta}-amyloid-modulated$ acetylcholine (ACh) release from the hippocampal slices were examined. It was found that inclusion of $Rb_1$ (0.1 ${\mu}M$), but not $Rg_1$, can attenuate ${\beta}-amyloid-suppressed$ ACh release from the hippocampal slices. Our results demonstrated that $Rb_1\;and\;Rg_1$ are the key components involved in various beneficial effects of GS but they may elicit their effects through different mechanisms.

Recently, we have provided evidence that ginsenosides, the active components of Panax ginseng, utilize pertussis toxin (PTX)-insensitive $G{\alpha}_{q/11}-phospholipase\;C-{\beta}3(PLC-{\beta}3)$ signal transduction pathway for the enhancement of $Ca^{2+}-activated\;Cl^{-}$ current in the Xenopus oocyte (British J. Pharmacol. 132, 641-647, 2001; JBC 276, 48797-48802, 2001). Other investigators have shown that stimulation of receptors linked to $G{\alpha}-PLC$ pathway inhibits the activity of G proteincoupled inwardly rectifying $K^+$ (GIRK) channel. In the present study, we sought to determine whether ginsenosides influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocyte injected with GIRK 1/4 channel cRNAs, bath-applied ginsenosides inhibited high potassium (HK) solution-elicited GIRK current $(EC_{50}:4.9{\pm}4.3\;{\mu}g/ml).$ Pretreatment of the oocyte with PTX reduced the HK solution-elicited GIRK current by $49\%,$ but it did not alter the inhibitory ginsenoside effect on GIRK current. Prior intraoocyte injection of cRNA(s) coding $G{\alpha}_q,\;G{\alpha}_{11}\;or\;G{\alpha}_q/G{\alpha}_{11},\;but\;not\;G{\alpha}_{i2}\;or\;G{\alpha}_{oA}$ attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding $G{\beta}_{1{\gamma}2}$ also attenuated the ginsenoside effect. Similarly, injection of the cRNAs coding regulators of G protein signaling 1, 2 and 4 (RGS1, RGS2 and RGS4), which interact with $G{\alpha}_i\;and/or\;G{\alpha}_{q/11}$ and stimulates the hydrolysis of GTP to GDP in active GTP-bound $G{\alpha}$ subunit, resulted in a significant reduction of ginsenoside effect on GIRK current. Preincubation of GIRK channel-expressing oocyte in PLC inhibitor (U73122) or protein kinase C (PKC) inhibitor (staurosporine or chelerythrine) blocked the inhibitory ginsenoside effect on GIRK current. On the other hand, intraoocyte injection of BAPTA, a free $Ca^{2+}$ chelator, had no significant effect on the ginsenoside action. Taken together, these results suggest that ginsenosides inhibit the activity of GIRK 1/4 channel expressed in the Xenopus oocyte through a PTX-insensitive and $G{\alpha}_{q/11}$-,PLC-and PKC-mediated signal transduction pathway.

In the present study, we have investigated the effects of centrally administered ginsenoside Rc or Rgl on the modulation of NMDA receptor and $GABA_A$ receptor binding in rat brain. The NMDA receptor binding was analyzed by quantitative autoradiography using $[^3H]MK-801$ binding, and $GABA_A$ receptor bindings were analyzed by using $[^3H]muscimol\;and\;[^3H]flunitrazepam$ in rat brain slices. Rats were infused with ginsenoside Rc or Rg1 ($10\;{\mu}g/10{\mu}l/hr$, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2ML), The levels of $[^3H]MK-801$ binding were highly decreased in part of cortex and cingulated by ginsenoside Rc and Rgl. The levels of $[^3H]muscimol$ binding were strongly elevated in almost all regions of frontal cortex by the treatment of ginseoside Rc but decreased by ginsenoside Rg 1. However, the $[^3H]flunitrazepam$ binding was not modulated by ginsenoside Rc or ginsenoside Rgl infusion. These results suggest that prolonged infusion of ginsenoside could differentially modulate $[^3H]MK-801\;and\;[^3H]muscimol$ binding in a region-specific manner. Also, we investigated the influence of centrally administered ginsenoside on the regulation of mRNA levels of the family of NMDA receptor subtypes (NR1, NR2A, NR2B, NR2C) by in situ hybridization histochemistry in the rat brain. The level of NR1 mRNA is significantly increased in temporal cortex, caudate putamen, hippocampus, and granule layer of cerebellum in Rgl-infused rats as compared to control group. The level of NR2A mRNA is elevated in the frontal cortex. In contrast, it was decreased in CAI area of hippocampus in Rgl-infused rats. However, there was no significant change of NR1 and NR2A mRNA levels in Rc-infused rats. The level of NR2B mRNA is elevated in cortex, caudate putamen, and thalamus in both Rc- and Rg-infused rats. In contrast, NR2B level is decreased in CA3 in Rgl-infused rats. The level of NR2C mRNA is increased in the granule layer of cerebellum in only Rg1 but not Rc infused rats. These results show that structure difference of ginsenoside may diversely affect the modulation of expression of NMDA receptor subunit mRNA after infusion into cerebroventricle in rats.

We investigated anti-hyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On Day 5, 150 mg/kg extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice $(156{\pm}9.0\;mg/dl\;vs.\;243{\pm}15.8mg/dl,$ P<0.01). On Day 12, the extract-treated ob/ob mice became normoglycemic $(137{\pm}6.7\;mg/dl)$ and had significantly improved glucose tolerance. The overall glucose excursion during the two-hour intraperitoneal glucose tolerance test (IPGTT), calculated as area under the curve (AUC), decreased by $46\%$ (P<0.01) compared to vehicle-treated ob/ob mice. Glucose levels of lean mice were not significantly affected by the extract. The improvement in blood glucose levels in 150 mg/kg extracttreated ob/ob mice was associated with significant reduction in serum insulin levels of fed and fasting mice. Consistent with an improvement in insulin sensitivity, hyperinsulinemic euglycemic clamp study revealed a more than 2-fold increase in the rate of insulin-stimulated glucose disposal in treated ob/ob mice $(112{\pm}19.1\;vs.\;52{\pm}11.8{\mu}mol/kg/min$ for the vehicle group, P<0.01). In addition, 150 mg/kg extract-treated ob/ob mice, but not the lean mice, lost significant weight (from $51.7{\pm}1.9g\;on\;Day\;0\;to\;45.7{\pm}1.2$ on Day 12, P<0.01 compared to vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P<0.05) and a very significant increase in energy expenditure (P<0.01) and body temperature (P<0.01). A 12-day treatment with 150 mg/kg Panax ginseng berry extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re, a major constituent of the ginseng berry, but not from the root, plays a significant role in anti-hyperglycemic action. This anti-diabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism. The identification of a significant anti-hyperglycemic activity in ginsenoside Re may provide an opportunity to develop a novel class of anti-diabetic agent.

Since immemorial time Panax ginseng has been known as therapeutic, tonic, prophylactic and restorative agent in ancient Korea, China and Tibet and at present time is also used as a food supplement by Western societies (6). Various ginseng preparations in a form of powders, teas, tinctures or extracts, very often mixed with other substances are recommended for attenuation of degenerative processes caused by aging or fatigue, as well as for treatment of various disorders and diseases in several organs (e.g. circulatory and nervous system, liver, kidney). One of the most commonly known properties of ginseng is its possibly positive influence on physical and mental performance and general well being. Because of these adaptogenic properties promoting vitality and resistance to stress ginseng is considered as an ergogenic aid. During almost 40 years in many laboratories attempts have been made to find out whether ginseng can be 'a remedy for today's problems'. The present work is focused on the results obtained in human studies and concerning an influence of ginseng root extracts on exercise and mental performance.

The effect of Panax ginseng administration in muscle inflammatory process induced after eccentric exercise, that causes myofibrillar disruption, was studied. Changes in lipid peroxidation, inflammation, glycogen levels in muscle and release of myocellular proteins to blood were measured. The analyses were performed immediately after eccentric exercise and over week since this period are necessary for the muscle damage-repair cycle. The ginseng extract $(100\;mg\;kg^{-1})$ was orally administered to rats for three months, before the eccentric exercise performance. The results showed the protective role of ginseng against skeletal muscle damage. This effect could be associated with their membrane stabilising capacity since creatine kinase (CK) activity was significantly decreased 96 h post-exercise from $523{\pm}70\;to\;381{\pm}53$ and 120 h post-exercise from $443{\pm}85\;to\;327{\pm}75$ in treated animals. ${\beta}-glucuronidase$ activity, as indicator of inflammation, showed a significant reduction of about $15-25\%$ in soleus, vastus and triceps in these post-exercise times. The lipid peroxidation, measured by malondyaldehyde levels, was significantly decreased in the 24 h postexercise period in soleus and vastus intermedius muscles and on the recovery period. Finally ginseng administration reduced significantly the decrease of the glycogen levels immediately after exercise and when the regenerative process took place (72-168 h post exercise). Collectively, the results have showed that ginseng did not inhibit the vital inflammatory response process associated with the muscle damage-repair cycle but presumably ameliorate the injury.

Objective; Antistress effect of Korean red ginseng (RG) on postmenopausal women with severe climacteric syndrome (CS) were evaluated from the viewpoint of traditional KAMPO-medicine and Western medicine. Methods; All patients with CS were treated with daily oral administration of 6g RG for 30 days. Nine patients with CS were evaluated with the use of diagnostic scores for KI-deficiency (deficiency of vital energy) and OKETSU (blood stagnation) syndrome from the viewpoint of KAMPa-medicine. In the same patients with CS, peripheral blood levels of $\beta$-endorphin and total plasminogen activator inhibitor-1 (t-PAI-1) were measured before and after treatment with RG. In another group, 12 patients with CS, psychological test using CMI, STAI and SDS were performed from the viewpoint of Western medicine. Stress related hormones, such as ACTH, cortisol and DHEA-S in those 12 patients with CS were also measured before and after treatment with RG. Results; KI-deficiency score and OKETSU score in patients with CS were significantly (p<0.001) higher than those in patients without CS. After treatment with RG, both scores were markedly (p<0.001) decreased compared to before treatment with RG. ${\beta}-endorphin$ levels in patients with CS were significantly (p<0.05) higher than those in patients without CS. Total PAI-I levels in patients with CS were increased before treatment with RG. No significant difference, however, were observed between patients with and without CS. After treatment with RG, both levels of ${\beta}-endorphin$ and total PAI-l in patients with CS were significantly (p<0.01 and p<0.05, respectively) decreased compared to before treatment with RG. CMI and STAI scores in patients with CS were significantly (p<0.05) higher than those in patients without CS. SDS scores in patients with CS were also markedly (p<0.001) higher than in those without CS. After treatment with RG, all scores decreased within normal range. DHEA-S levels in patients with CS were about a half of those without CS. Consequently, cortisol/DHEA-S (C/D) ratio was significantly (p<0.001) higher in patients with CS than in those without CS. Although the decreased DHEA-S levels were not restored to the levels in patients without CS, the C/D ratio decreased significantly (p<0.05) after treatment with RG. Conclusion; Reinforcement of vital energy and improvement of stagnant blood circulations by oral administration of RG were elucidated from the viewpoint of traditional KAMPO-medicine. From the viewpoint of Western medicine, effect of RG on postmenopausal women with CS seemed to be brought about in part by not only an improvement of psychoneuroendocrine dysfunctions but also an amelioration of blood coagulation systems.

We have found many beneficial effects of the long-tenn intake of Korean red ginseng (KRG) in human immunodeficiency virus (HIV) type-I infected patients, including the maintenance of CD4+ T cell count for 10 years with KRG only and the delayed development of resistance mutation to ZDV. In this study, to investigate whether KRG-intake could affect the clinical progression and nef gene variation, we determined 200nef sequences from 70 patients. Follow-up period was $8.8{\pm}2.9$ years and annual decrease in CD4+T cell was $41{\pm}57/ul.$ Nested polymerase chain reaction (PCR) and direct sequencing were perfonned with peripheral blood mononuclear cells (PBMC) obtained at times during the study period. First, there was a significant correlation between survival duration and duration of KRG-intake $(36.8{\pm}38$ months)(P=0.000). There were significant correlations between the last NefProg score and CD4+ T cell count (r= 0.208, P<0.05) and annual decrease in CD4+ T cell count (r =0.346, P<0.01) in 70 patients. In addition, there were significant correlations between KRG-intake and annual decrease (r= 0.323, P<0.01), and the CD4+ T cell count itself (r=0.229, p<0.05). Furthennore, there was also a mild significance between the NefProg score and the duration of KRG-intake in only SP and RP (n=30, r=-0.281, P=0.067). In addition, we detected various defects in 21 patients $(30.0\%),$ not including 5 premature stop codons. Ten $(12.5\%)$ patients showed repeated deletion of an amino acid. Four of 10 patients were gross deletions and they were treated with KRG for more than 20 months. The number of patients with repeated gross deletions was significantly higher in the order of slow progressors $(18\%)$, typical progressors($3\%$), and rapid progressors($0\%$) (P<0.05). We also observed that long-tenn intake of KRG might make the change from A or D to T at position 54 and decrease NefProg score. Taken together, our results show clear evidence that the long-term intake of KRG has effects on nef gene variation as well as definite clinical usefulness.

North American ginseng production may have been maximized in the traditional growing areas in the last decade and further increases may be in woods grown root, for niche markets. The marketplace demands high quality roots. Most problems leading to low quality roots start with the grower and can be avoided. These include poor site selection, inadequate soil drainage, untimely and poorly applied pesticides, and neglect of good sanitary practices. Selection of low lying sites increased the plant damage from frost in Ontario in May 2002. Seeding is still the major method of propagation of ginseng in spite of some success in culturing different parts of the plant. Opportunities exist for shortening the stratification period of North American ginseng seed to allow spring planting. This may reduce disease incidence. Since only one-third of ginseng seed sown ultimately produces plants harvested after 3 years any approach that reduces disease incidence and improves seed germination, seedling emergence and crop stand must be pursued. Disease is the major problem in ginseng cutivation from seed stratification, soil preparation prior to planting, right through to drying of the roots. Replant disease remains as an unresolved problem and needs full characterization and new approaches for control. Much progress has been made in research and related extension activities in disease control although challenges will arise such as with Quintozene and its replacement with Quadris for control of diseases caused by Rhizoctonia. Decreased labor populations and increased associated costs for ginseng production are causing rapid mechanization in every aspect of the ginseng industry. Engineers, machinery dealers, and fabricators, and growers are being challenged to increase efficiency by mechanization.

One prominent characteristic of2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) toxicity in rats is a reduction of body weight accompanied by an altered serum lipid profile such as hyperlipidemia. A single administration of TCDD (50 ug/kg) resulted in a decrease of body weight and increase of serum cholesterol in rats. TCDD-induced weight loss and serum cholesterol elevation was reduced in rats administered with water extract (100 mg/kg) or saponin fraction (40 mg/kg) of Panax ginseng C.A.Meyer. In contrast, the administration of Panax quinquefolium did not inhibit the TCDD-induced weight loss and serum cholesterol elevation. Histological examinations of liver and testis revealed the administration of saponin fraction of Panax ginseng attenuated the TCDD-induced hispathologicallesions whereas the administration of saponin fraction of Panax quinquefolium did not. High performance liquid chromatographic analysis demonstrated high percentiles of ginsenoside Rg and ginsenoside $Rh_1$ were evident in saponin fraction of Panax ginseng. Results indicate that the protective effects of Panax ginseng, not Panax quinquefolium, on the TCDD-induced toxicity might be resulted from different compositions of saponins in Panax ginseng.

In order to screen out indicators for the discrimination of ginseng habitat, some physical and chemical characteristics of Korean red ginsengs (94 kinds) and Chinese red ginsengs (50 kinds) were analyzed by using a rheometer, an electronic nose system, a combined technique of solid phase micro-extraction (SPME) and gas chromatograph equipped with an electron capture detector (GC/ECD), an X-ray fluorescence spectrometer (XRF), an inductively coupled plasma mass spectrometer (ICP/MS), a near infrared spectrometer (NIRs) and high performance liquid chromatography equipped with evaporative light scattering detector (HPLC/ELSD). The results are summarized as follows: (i) The rhizome strengths of Korean red ginsengs were significantly higher than those of Chinese red ginsengs. (ii) The electronic nose patterns of Korean red ginsengs were significantly different from those of Chinese red ginsengs. (iii) Some unidentified peaks were detected not in the headspace of Korean red ginsengs but in the headspace of Chinese red ginsengs when the headspace volatiles prepared by the SPME technique were analyzed by GC/ECD. (iv) Either the content ratios of K to Ca or Mn to Fe were significantly different between Korean red ginsengs and Chinese red ginsengs. (v) The reflectance ratios of NIRs wavenumbers such as $904\;cm^{-1}\;to\;1088\;cm^{-1}$ for Korean red ginsengs were significantly different from those for Chinese red ginsengs. (vi) The content ratios of ginsenoside-Rg to ginsenoside-Re of Korean red ginsengs were significantly higher than those of Chinese red ginsengs. These results indicate that the rhizome strength, the electronic nose pattern, the occurrence of ECD-sensitive headspace volatile components, the content ratios of K to Ca and Mn to Fe, the NIRs pattern and the content ratio of ginsenoside-Rg to -Re may be indicators for the discrimination of ginseng habitat.

To follow the metabolic fate of aglycone of ginseng saponins,in vitro and in vivo experiments were performed. Incubation of 20(S)-prtopanaxatriol (1) with rat liver S9 fraction afforded unique ocotillol derivatives, 20, 24-epoxysides (3 and 4). Also 20(S)-prtopanaxadiol (2) gave the corresponding epoxides (5). Healthy volunteers were taken with Sanchi Ginseng, which contains protopanaxatriol and protopanaxadiol saponins and no ocotillol saponins. From the alkaline hydrolysate of the urine samples of these volunteers,3 was detected as well as 1, and the ratio of 3/1 increased up to 2.0 at the maximum at 50 hrs. Biochemical significance of the ocotillol derivatives is discussed, since the main bioactive saponin in Panax vietnamensis is an ocotillol-type saponin, majonoside R2 (7).

A red ginseng acidic polysaccharide(RGAP) with immunomodulating antitumor activities was isolated from Korean red ginseng, The molecular weight of RGAP was estimated to be 12-450 kDa by gel filtration chromatography, RGAP was found to increase survival rate and to inhibit of tumor growth significantly in a dose dependent manner in mice transplanted with tumor cells. RGAP significantly promoted nitric oxide(NO) production from peritoneal macrophages bothin vivo and in vitro. Western blot analysis exhibited a newly synthesized inducible nitric oxide synthase(iNOS) protein band in the RGAP treated group. It seems likely that immunomodulating antitumor activities of RGAP are mainly mediated by NO production of macrophage. RGAP was further purified by ultrafiltration and anion exchange chromatography on DEAE-sepharose, followed by gel filtration on Sephacryl S-300 to give an active fraction(GFP) with stronger NO production in murine macrophages. GFP increased survival rate ten times compared to RGAP in male ICR mice transplanted with sarcoma 180 and also showed more potent tumoricidal activities of natural killer cells than RGAP. Sugar $composition(mol\%)$ of GFP was found to be arabinose:rhamnose:xylose:galacturonic acid:mannose:galactose:glucose(10:9:1:25:8:20:27) by GC/MS. The results suggest that clinical trials of RGAP in immunotherapy against cancer are highly feasible.

The chemopreventive effects of ginseng on rat carcinogenesis models were investigated, In the present study, the inhibitory effects of white and red ginseng on tumor development were examined using medium-term liver, initiation and medium-term multi-organ carcinogenicity bioassay systems. No modifying potential of the ginsengs was evident in terms of the numbers or areas of glutathione S-transferase placental form (GST -P)-positive foci, which is a marker of preneoplastic lesion in rat livers. However, white ginseng, but not red ginseng was found to decrease the incidences of adenocarcinoma of the small intestine and colon in the medium-term multi-organ carcinogenesis model. These results indicate that white ginseng may have inhibitory effects on progression stage of rat intestinal carcinogenesis, but the influence is not strong. Ginseng is unlikely to have promoting or inhibitory effects in other organs under the present type of experimental conditions. Possible application on ginseng for chemoprevention of colon cancer in humans, can be concluded given the lack of obvious adverse effects.

In this paper, we present evidence that the red ginseng from Panax ginseng C.A. Meyer inhibits the recurrence of advanced gastric cancer and shows immunomodulatory activities during postoperative chemotherapy. Flow cytometric analyses for peripheral T-lymphocyte subsets showed that the red ginseng powder restored CD4 levels to the initial preoperative values during postoperative chemotherapy. Depression of CD3 during postoperative chemotherapy was also inhibited by the red ginseng powder ingestion. This study demonstrated a 5-year disease free survival and overall survival rate that was significantly higher in patients taking the red ginseng powder during postoperative chemotherapy vs. control $(68.2\%\;vs.\;33.3\%,\;76.4\%\;vs.\;38.5\%,$ respectively, p<0.05). The mean value of serum IL-10 of the ginseng group was reduced progressively during the postoperative chemotherapy. The values of the ginseng group were close to that of the control group on postoperative months 3. These studies suggest that the red ginseng may have some immunomodulatory properties associated with CD3 and CD4 activity and interleukin 10 during postoperative chemotherapy and some potential of improving prognosis in patients with advanced gastric cancer.

Ginsenosides are metabolized (deglycosylated) by intestinal bacteria to active forms after oral administration. 20(S)-Protopanaxadiol $20-O-{\beta}-D-glucopyranoside$ (M1) and 20(S)-protopanaxatriol (M4) are the main intestinal bacterial metabolites (IBMs) of protopanaxadiol- and protopanaxatriol-type glycosides. M1 was selectively accumulated into the liver soon after its intravenous (i.v.) administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EMl) in the liver. EM1 was isolated from rats in a recovery dose of approximately $24mol\%.$ Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as Ml was, it was accumulated in the liver longer than M1. The in vitro cytotoxicity of M1 was attenuated by fatty acid esterification, implying that esterification is a detoxification reaction. However, esterified M1 (EM1) inhibited the growth of B16 melanoma more than Ml in vivo. The in vivo antitumor activity paralleled with the pharmacokinetic behavior. In the case of M4, orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its spreading to other organs in the body and excretion as bile. The administration of M4 prior to tumor injection abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GMl. Both EM1 and EM4 did not directly affect tumor growth in vitro, whereas EM1 promoted tumor cell lysis by lymphocytes, particularly non-adherent splenocytes, and EM4 stimulated splenic NK cells to become cytotoxic to tumor cells. Thus, the esterification of IBM with fatty acids potentiated the antitumor activity of parental IBM through delay of the clearance and through immunostimulation. These results suggest that the fatty acid conjugates of IBMs may be the real active principles of ginsenosides in the body.

Earlier studies have demonstrated that chromium (Cr) VI compounds have been shown to be more toxic and carcinogenic than other chromium compounds. The aim of the present work was to evaluate the antioxidant effects of red ginseng against chromium VI -induced toxicity and free radical generation. Sixty adult male rats were divided into six equal groups include: control group, group received Cr VI alone (50 mg/kg b.w.), group treated with Korean ginseng (K. ginseng) alone (20 mg/kg b.w), group treated with Cr VI for 15 days then received K. ginseng for other 15 days, group treated with Cr VI and K. ginseng at the same time for 15 days, and group treated with K. ginseng for 15 days then Cr VI for other 15 days. The results revealed that Cr VI caused significant increase in ALT, AST, ALP, G-GT, urea, creatinine, and acid phosphatase. Whereas, it caused significant decrease in TP, albumin, testosterone, GPX, and SOD indicating a stress for liver, kidney and testes. K. ginseng alone caused significant increase in GPX and SOD activities in healthy animals and this result suggests a prophylactic role for this herb in protection against the damaging impact induced by free radical species. Furthermore, the other biochemical parameters measured after K. ginseng administration were comparable to the control values. Treatment with Cr VI followed by K. ginseng, Cr VI and K. ginseng or K. ginseng followed by Cr VI resulted in significant improvement in all tested parameters towards the normal values of the controls. However, this improvement was pronounced in the group pre-treated with K. ginseng for 15 days before Cr VI administration. It could be concluded that K. ginseng exhibited a protective action against the toxic effects of Cr VI and it had the ability to scavenge free radicals resulted from Cr VI intoxication.

There has been continuing interest in the development of synthetic and natural compounds that modify the immune response particularly for the treatment of AIDS and cancer. During the past fifty years, numerous scientific studies have been published on ginseng (Foster and Chongxi, 1992). Modern human studies have investigated preventive effect of ginseng on several kinds of cancer (Yun et al, 1993,Yun, 1995,Yun and Choi, 1998), its long term immunological effect on HIV patients (Sankang, 1989, Cho et al, 1997), its effect on cell mediated immune functions in healthy volunteers (Scaglione et al, 1990). Similarly non clinical studies on animal model system have studied the chemopreventive action of ginseng on cancer (Kumar, 1993,98) and immunological properties of ginseng (Kim et al, 1990, Tomoda et al, 1993, Yun et al, 1993, Mizuno et al, 1994,Lee et al, 1997, Park et al, 2001,Yoshikawa et al, 2001, Wang et al, 2001). The precise mechanism of action of ginseng, however, not clearly understood. Considering its wide-ranging therapeutic effects, this study is being undertaken to elucidate the general mode of action of ginseng, especially to test our hypothesis that its biological action may be mediated by the immune system.

Object To find out which of the 27 ginsenosides isolated from Panax ginseng C.A. Mey that may inhibit the proliferation of human osteosaocoma cell line $U_2OS$. Methods Effects of each individual ginsenoside on the proliferation of $U_2OS$ cell were studied by determining the viability of cancer cells during culture with or without the presence of the test compound. DNA assay was determined by flow cytometry. Results Ginsonosides -Ro, $-Rh_l,\;-Rh_2,\;-F_1\;and\;-L_8$ at concentrations of 5 ,umol/L could obviously suppress the proliferation of $U_2OS$ cells while ginsenosides $-Rg_1,\;-F_3,$ -Rf, PPT and PT significantly inhibited the cancer cells. Flow cytometry revealed that ginsenosides $-Ro,-Rg_1-Rf,-F_1-Rh_2,PPT$ and PT induced cell cycle arrest at $G_0/G_1$ phase with obvious decrease of cell count at Sand $G_2+M$ phase, Moreover, ginsenosides $-Rf_1,-Rg_1,\;-F_1$ and PPT induced significantly high rates of cell death as compared with the control. Conclusion These data suggested that ginsenosides inhibited $U_2OS$ proliferation Via cell cycle arrest or induction of cell death.

Panax ginseng (family- Araliaceae) is a native plant of Korea and has been used for past several years among oriental people. To evaluate the radioprotective potential of P. ginseng on the formation of giant cells in the testis of Swiss albino mice, the animals were divided into four groups: -(I)-Only vehicle was administered. (II)P. ginseng treated group: -The animals received 10 mg/kg body weight P. ginseng root extract (in DDW) i.p. continuously for 30 days. (III) Irradiated group: -The animals were exposed to 8 Gy gamma radiation at the dose rate of 1.69 Gy/min at the distance of 80 ems. (IV) Combined treatment group: -Animals were given P. ginseng extract for four days and on fourth day they were irradiated to 8 Gy gamma radiation after 30 minute of extract administration. The animals of these three groups were autopsied on day 1,3, 7, 14 and 30 days. In ginseng treated group, active spermatogenesis was observed without any toxic effect. Histopathological studies of irradiated group (II) revealed reduction in germ cell count, loss of sperms and formation of multinucleated giant cells on day 7th. These giant cells were formed by round nuclei of early or late spermatids. In combination group (III), although germinal epithelium was still disorganized with loss of cells in few tubules, but no giant cell formation was observed. In order to know the mechanism of radioprotection of ginseng, LPO and GSH were estimated. It was observed that pretreated irradiated animals showed inhibition of LPO and increase in GSH. Thus the present study suggests ginseng protects male gonads. This may be attributed to the inhibition of LPO and increase synthesis of GSH byginseng.

We have previously found that the saponins but not other components in the ginseng reduce the secretion of catecholamines (CAs) from bovine adrenal chromaffin cells, a model of sympathetic nerves, evoked by acetylcholine (ACh) due to the blockade of $Na^+$ influx through nicotinic ACh receptor-operated cation channels, and it has been concluded that the inhibitory effect may be associated with the anti-stress action of ginseng. However, the saponins, which showed the great reduction of the CA secretion, were mainly the protopanaxiatriols. The protopanaxadiol and oleanolic acid saponins had a little or little such effect. Recent studies demonstrated that the oligosaccharides connected to the hydroxyl groups of the aglycones of the saponins are in turn hydrolyzed by gastric acid and enzymes in the intestinal bacteria when the ginseng is orally administrated. In this study, the effects of their major 6 kinds of metabolites on the secretion of CAs were investigated. All metabolites (M1, 2, 3 and 5 derived from the protopanaxadiols, and M4 and 11 from the protopanaxiatriols) reduced the ACh-evoked secretion from the cells. In the metabolites, the M4 inhibition was the most potent ($IC_{50}({\mu}M):M4(9)$ < M2 (18) < M3 (19) < M1l (22) < M5 (36) < MI (38)). Although M4 also reduced the CA secretion induced by high $K^+$, a stimulation activating voltage-sensitive $Ca^{2+}$ channels, the inhibitory effect was much less than that on the ACh-evoked secretion. M4 inhibited the ACh-induced $Na^+$ influx into the cells in a concentration-dependent manner similar to that of the inhibition of the ACh-evoked secretion. When the cells were washed by the incubation buffer after the preincubation of the cells with M4 and then incubated without M4 in the presence of ACh, the M4 inhibition was not completely abolished. On the other hand, its inhibition was maintained even by increasing the external ACh concentration. These results indicate that the saponins are metabolized to the more active substances in the digestive tract and the metabolites attenuate the secretion of CAs from bovine adrenal chromaffin cells stimulated by ACh due to the noncompetitive blockade of the ACh-induced $Na^+$ influx into the cells. These findings may further explain the anti-stress action of ginseng.

Lim and his coworkers (1987; 1988; 1989) have also found that all of total Ginseng saponin, panaxadiol-and panaxatriol-type saponins cause the increased secretion of catecholamines (CA) in a $Ca^{2+}$ -dependent fashion from the isolated perfused rabbit adrenal glands through the activation of cholinergic (both nicotinic and muscarinic) receptors. These CA secretory effects are partly due to the direct action on the rabbit adrenomedullary chromaffin cells. However, the present study was designed to examine the effect of total ginseng saponin on CA secretion evoked by activation of cholinergic nicotinic receptors in the isolated perfused model of the rat adrenal gland. Total ginseng saponin given (100 ${\mu}g$/20 min) into an adrenal vein did fail to produce alteration of spontaneous CA release from the rat adrenal medulla. Acetylcholine(5.32 mM)- and DMPP(100 ${\mu}M$, a selective nicotinic receptor agonist)-evoked CA secretory responses were reduced markedly after the pretreatment with the total ginseng saponin at a rate of 100 ${\mu}g$/6.2 ml/20 min, respectively. Pretreatment with total ginseng saponin also depressed greatly high potassium (56 mM, a membrane depolarizing agent)- and Bay-K-8644 (10 ${\mu}M$, a calcium channel activator)-induced CA secretions. Taken together, it is thought that total ginseng saponin can inhibit the releasing effect of CA evoked by nicotinic receptor stimulation from the isolated perfused rat adrenal medulla, which seems to be associated to the direct inhibition of influx through L-type calcium channel into the rat adrenomedullary chromaffin cells. It seems that there is species differences in the adrenomedullary catecholamine secretion between the rabbit and rat.

Diabetes mellitus is reaching epidemic proportions worldwide. The insufficiency of medication to cope with this burden has coincided with a dramatic rise in the prevalence of use of complementary and alternative therapies, especially herbal treatments. This surge in demand presents a challenge to prove the safety and efficacy of these treatments in diabetes. Korean red ginseng (steam treated Panax ginseng C.A. Meyer) is a strong candidate to succeed. It has been shown to possess a multitude of hypoglycemic effects and improve metabolic disturbances related to diabetes in in vitro and animal models. Data in humans is also emerging to support these benefits. Whether these results can be replicated in a rigorous clinical testing program is unclear. We therefore investigated the antidiabetic effects of Korean red ginseng in a series of 2 acute and 1 longterm randomized, double-blinded, placebo-controlled clinical trials. This paper provides the rationale for this program of study, expanding on the problem of diabetes, its management, and the possible role for Korean red ginseng. It then describes the design and expected findings.

Wild ginseng production is increasing due to forest recovery for last 30 years. Total number of Symmani (traditional mountain ginseng digger) was 558 in 2001. Provincial distribution of Symmani in 2001 was highest in Kangwon $(32\%),$ next in Choongbook $(21\%)$ and least in Jeonnam $(0.7\%)$ and Kyoungnam $(0.9\%).$ Age distribution of Symmani was $33\%\;for\;fourties,\;32\%$ for fifties and $20\%$ for sixties. There were 8 persons in eighties. Symmanies are still keeping traditional ritual for mountain god serving clothes of colored ribbons and foods. Increased production induced open market system from underground dealing of mountain ginseng. Korea Mountain Ginseng Association established mountain ginseng assessment committee with professional Symmanies in 2001. From September to November in 2001, 987 roots were requested for quality assessment to the committee and 476 roots $(48\%)$ were passed and graded and others were rejected. Highest frequency of rejection was foreign origin. Pass rate was highest $(74\%)$ in Choongnam suggesting best place for quality. Number of collected roots in each province was positively correlated (p=0.05) with number of Symmanies. There are 3 quality groups of mountain ginseng, Heaven (pure natural), Earth (from seeding of wild ginseng) and Man (from seeding or seedling of wild ginseng with slight environmental modification). The relationship between price and age was polynomial in high quality root, Heaven, Earth and seed long head of Man group, and linear in low quality group, seedling long head of Man. The best one in 2001 was 26 g, 124 years old and sold with 109 million won. Quality criteria are age, shape, weight, color and healthy outlook. Fine roots are criteria for health status of roots and taproot is criteria for efficacy and called as medicine barrel. The implication is that ginsenosides have rarely been experienced for efficacy. The quality criteria of cultivated ginseng were originated from those of mountain ginseng. It is unique for mountain ginseng that only fresh one can be on market. Since quality criteria of mountain ginseng must be based on the efficacy experience it is well expected that present criteria might almost be established at the age of Shinnong Materia Medica.

A large number of individual ginseng plants have been selected in the farmer's fields to develop new ginseng varieties with desirable traits since 1970s. Among them, Hwangsukjong with green stem and yellow berry was selected as a ginseng germplasm. The phenotype of Hwangsukjong is quite different from Jakyungjong that has violet stem and red berry and has been cultivated in most of ginseng fields. Therefore, Hwangsukjong was crossed with Jakyungjong to clarify the inheritance of stem color and then the characteristics of $F_1\;and\;F_2$ hybrids were investigated. $F_1$ hybrid plants were similar to Jakyungjong in most of aerial part characters and showed hybrid vigor in fresh weight of root and weight of 100 seeds. In $F_2$ generation, the stem color was segregated in a ratio of 3 violet to 1 green. From this result, it was elucidated that violet color was controlled by single dominant gene. In another experiment, DNA was extracted from parents (Jakyungjong and Hwangsukjong) and $F_1$ hybrid. For each primer evaluated, multiple band profile was produced comprising from one to five major bands plus a varying number of minor bands and amplified bands were detected among most primers. In case of UBC primer number 13, 17, 30, 31, and 43, band patterns of parents and $F_1$ hybrid were very similar, but the others were not. Especially, in {\sharp}1$, {\sharp}4$, and {\sharp}33$, specific band was produced in Hwangsukjong and $F_1$ hybrid while in {\sharp}6$, another specific band was produced in Jakyungjong and $F_1$ hybrid. Therefore, $F_1$ hybrid had all specific bands at these primers. So, these selective markers could be used for identification of characteristics of $F_2$ hybrids

In different approaches ginsenosides were extracted from Korean ginseng roots by ammonia and for comparison with methanol-water and water. The extracts have been analyzed qualitatively and quantitatively to evaluate yield and selectivity of extractions of ginsenosides. Water supplied the lowest yield. The yields of extracts with liquid ammonia were higher than those with methanol-water. However, this is partly due to the conversion of malonyl ginsenoside to normal ginsenosides by ammonia. It was proved by HPLC that malonyl-ginsenosides $m-Rb_1,\;m-Rb_2,$ m-Rc and m-Rd were converted to the corresponding neutral ginsenosides. Furthermore, ginsenosides from ginseng roots were extracted by alkaline methanol-water $(60\%)$ solutions. Alternatively, the extracts of the methanol-water $(60\%)$ extraction were treated with sodium hydroxide solution. Both methods also convert the malonyl-ginsenosides to neutral ginsenosides.

A cross-examination between KT&G Central Research Institute and Guangzhou Institute for Drug Control was carried out in order to select optimum conditions for extraction, separation and determination of ginsenosides in red ginseng and to propose a better method for the quantitative analysis of ginsenosides. The optimum extraction conditions of ginsenosides from red ginseng were as follows: the extraction solvent, $70\%$ methanol; the extraction temperature, $100^{\circ}C;$ the extraction time, 1 hour for once; and the repetition of extraction, twice. The optimum separation conditions of ginsenosides on the SepPak $C_{18}$ cartridge were as follows: the loaded amount, 0.4 g of methanol extract; the washing solvents, distilled water of 25 ml at first and then $30\%$ methanol of 25 ml; the elution solvent, $90\%$ methanol of 5 ml. The optimum HPLC conditions for the determination of ginsenosides were as follows: column, Lichrosorb $NH_2(25{\times}0.4cm,$ 5${\mu}m$, Merck Co.); mobile phase, a mixture of acetonitrile/water/isopropanol (80/5/15) and acetonitrile/water/isopropanol (80/20/15) with gradient system; and the detector, ELSD. On the basis of the optimum conditions a method for the quantitative analysis of ginsenosides were proposed and another cross-examination was carried out for the validation of the selected analytical method conditions. The coefficient of variances (CVs) on the contents of ginsenoside-$Rg_{1}$, -Re and $-Rb_1$ were lower than $3\%$ and the recovery rates of ginsenosides were $89.4\~95.7\%,$ which suggests that the above extraction and separation conditions may be reproducible and reasonable. For the selected HPLC/ELSD conditions, the CVs on the detector responses of ginsenoside-Rg, -Re and $-Rb_1$) were also lower than $3\%$, the regression coefficients for the calibration curves of ginsenosides were higher than 0.99 and two adjacent ginsenoside peaks were well separated, which suggests that the above HPLC/ELSD conditions may be good enough for the determination of ginsenosides.

The strains of Panax ginseng C.A. Mey., P. quinquefolius L. and selected strains P. ginseng-B, P.ginseng-A, P. quinquefolius-C were investigated. Activities of SOD, catalase and peroxydase were determined by methods of Fridovich et al. (1979), Komov et al.(1975), Bovaird et al.(1982) respectively. Activities of SOD, catalase, peroxydase were investigated every day 5 in cycle of cultivation. For P. ginseng it was the 35 days, P. quinquefolius the 70 days, P. quinquefolius-C 90 days. P. ginseng-B 90 days, P. ginseng-A 60 days. The P. quinquefolius, P. quinquefolius-C, P. ginseng-B had clear differentiation and developed tracheid elements, which are absent in strain of P. ginseng. The peaks of protein content for P. ginseng (4.5 units/g) and for P. quinquefolius (3.5 units/g) were on day 10 and remained unchanged till the last cultivation. The strain P. ginseng-A had two peaks of protein content (2.5 mg/g) on day 15 and on day 30. For P. ginseng-B strain these peaks were on day 5 and day 40 (3.5 mg/g). Peroxydase activity peak (60 units/g) in P. ginseng strain was on day 10. This activity in P. ginseng-B had two peaks on day 15 and day 35 and reached 95 units/g , increasing to 150 units/g to day 80. In strain of P. ginseng-A was only one maximum of this activity -130 units/g on day 45. In P. quinquefolius peroxydase activity was 103 units/g on day 40, increasing to 135 units/g to day 90. For P. quinquefolius-C this activity peak was 136 units/g on day 60. Peroxydase activities for the upper and lower layers of biomass was different and varied considerably from 28-35 units/g in lower to 270-290 units/g for upper layer. The SOD activity had two peaks in P. ginseng strain the 80 units/g and the 70 units/g on day 20 and day 35 respectively. Activity of SOD in P. quinquefolius strain reached 53 units/g on day 40 and increased up to 83 units/g to day 60.The similar increase of SOD activity was marked for P. ginseng-B to 85 units/g on day 90. In P. ginseng strain the 6 molecular isoforms SOD was defined. One of them with RfO,6 was determined in all days of cycle, three other (Rf-0.43; 0.54;0.80) only on day 10 and day 20. The isoform of SOD with Rf-0,29 was detected only on day 10 and with Rf-0,35 only on day 35. The catalase activity decreased in all strains to the last days of cultivation. The changes of SOD, catalase and peroxydase activities reflect the differences between the strains of Panax ginseng and Panax quinquefolius and their selected forms. The correlation between maximum life span of strains and activities of their antioxydant enzymes were detected.

'The Regional complex long-term program of restoration (reintroduction) of Primoryes ginseng population up to 2005' elaborated by Primorye governor administration, Regional Committee of Natural Resources and Russian Academy of Sciences operates in Russian Primorye. The Institute of Biology and Soil Science (IBSS) provides the scientific implementation of this program including the genetic analysis of extant ginseng populations, plant reproduction and offspring identification. According to our investigations, the genetic resource of P. ginseng in Primorye is represented by three populations of wild-growing ginseng and a few private plantations. The results obtained by RAPD allowed concluding that this resource is dispersed among the wild and cultivated ginseng sub-populations in such a way that each of sub-populations studied has to be represented in living plant collection as a stock material to maintain species genetic variability. The allozyme analyses also showed that the small sub-populations of natural ginseng are characterized by unique genetic diversity and, therefore, they all need to be represented in reintroduction centers. Additionally the allozyme analysis discovered that the Blue Mountain and Khasan populations possess the most genetic diversity. So, at least one more reproductive ginseng unit has to be created besides two already existing reintroduction centers representing the Sikhote-Alin and the Blue Mountain populations.

We have already known, neural progenitor cells exist not only in the developing brain, but in certain spots in adult CNS in mammals, so it will be of great value to find out some compounds which can interfere these cells proliferation ability. In this research, we observed that ginsenoside $Rg_1$ can not only enhance neural progenitors' proliferation ability in vitro, but increase neurogenesis in adult mouse dentate gyrus in vivo. Firstly, we set up neural progenitor cells' culture system from embryonic rats' hippocampus and prove their feature through immunocytochemistry. Then by using MTT assay, we found that when growing with ginsenoside $Rg_1(0.5\~2.5{\mu}mol/l)$, the progenitor cells' survival rate nearly doubled, furthermore, we proved that this increase was due to the increment of cell proliferation through $^3H-thimidine$ incorporation assay, hence, we drew the first conclusion: ginsenoside Rg1 has the ability to stimulate neural progenitor cells' proliferation in vitro; in order to observe this compound's effect in vivo, we devised the following experiment: after administering ginsenoside Rg1 (5, 10 mg/kg, once a day) intraperitoneally for two weeks, we examine the number of BrdU positive cells in the dentate gyrus of mice, and found that Rg1 could increase the number of proliferation cells significantly in vivo. From these studies, we are quite sure about Rg1's effects on the proliferation ability of neural progenitor cells both in vitro and in vivo, certain targets of the compound and its underlying mechanisms are in progress.

Ginseng is the best known and most popular herbal medicine used worldwide. Ameliorating effects of ginseng were observed on the models of scopolamine-induced, aged or hippocampal lesioned learning and memory deficits. Further beneficial effects of ginseng were observed on neuronal cell death associated with ischemia or glutamate toxicity. In spite of these beneficial effects of ginseng on the CNS, little scientific evidence shows at the cellular level. In the present study, we have employed cultures of rat hippocampal neurons and examined the direct modulation of ginseng on NMDA receptor-induced changes in $[Ca^{2+}]_i$ and -gated currents using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques, respectively. We found that ginseng total saponins inhibited NMDA-induced but less effectively glutamate-induced increase in $[Ca^{2+}]_i$ Ginseng total saponins also modulated $Ca^{2+}$ transients evoked by depolarization with 50 mM KCI along with its own effects on $[Ca^{2+}]_i$. Among ginsenosides tested, ginsenoside $Rg_3$ was found to be the most potent component for ginseng actions on NMDA receptors. Furthermore, we examined the inhibitory effects ofbiotransformants of ginsenosides on NMDA receptor using purified stereoisomers of ginsenosides. 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_3$, produced the strongest inhibition while 20(S)-ginsenoside $Rh_1$ and Compound K produced the moderate inhibition on NMDA-induced increase in $[Ca^{2+}]_i$. The data obtained suggest that the inhibition of NMDA receptors by ginseng, in particular by 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_2$, could be one of mechanisms for ginsengmediated neuroprotective actions.

Ginsenosides of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol classification including the aglycones, PD, PI and ginsenosides Rh2, Rhl were shown to posses characteristic effects on proliferation of THP-l human leukaemia cells. A similar result was not apparent for ginsenoside Rg3 or dexamathasone. The concentration to inhibit $50\%$ of cells $(LC_{50})$ for PD, Rh2, PI and Rhl were 13 ${\mu}g/mL,\;15{\mu}g/mL,\;19{\mu}g/mL\;and\;210\;{\mu}g/mL$ respectively. Cell cycle analysis showed apoptosis with PD and PI treatment of THP-1 cells resulting in a build up of sub-G1 cells after 24, 48 and 72 hours of treatment. Rh2, and dexamathasone treatments also increased apoptotic cells after 24 hours, where as Rhl did not. After 48 and 72 hours Rh2, Rhl and dexamathasone similarly increased apoptosis, but these effects were significantly (P<0.05) lower than observed for both PD and PI treatments. Furthermore, treatments that produced the largest build up of apoptotic cells were also found to have the largest release of lactate dehydrogenase (LDH). It can be concluded from these studies that the presence of sugars to PD and PI aglycone structure reduces the potency to induce apoptosis, and alternately alter membrane integrity. These cytotoxic effects to THP-l cells were different from dexamethasone.