Ameliorating mechanisms of red ginseng on learning deficits were investigated in the following 3 experiments; its effects on 1) place learning deficits in aged rats and in young rats with selective hippocampal lesions (behavioral study), 2) long-term potentiation in the hippocampal formation (neuro- physiological study), and 3) ChAT (choline acetyl transferase) activity in various brain regions of aged rats (pharmacological study). In the behavioral study, first, performance in the place learning tasks were compared among 3 groups of young and aged rats; control young intact rats (10-12 week old) treated with water, aged rats (28-32 month old) treated with water, and aged rats (28-32 month old) treated with red ginseng (100 mghglday) suspended in water. Second, performance in the place learning tasks was compared among 3 groups of young rats; control intact rats treated with water, rats with bilateral hippocampal lesions treated with water, and rats with bilateral hippocampal lesions treated with red ginseng (100 mg/kg/day). Each rat in these 2 behavioral experiments was tested with the 3 types of the place learning tasks in a circular open field using intracranial self-stimulation (ICSS) as reward. The ICSS reward was delivered if the rat (1) moved distance of 100-160 cm (DMT): (2) entered an experiment-determined reward place within the open field, and this place was randomly varied in sequential trials (RRPST); or (3) entered 2 specific places, and did a shuttle behavior between the 2 places (PLT). Performance of the aged rats in the ginseng group was not significantly different from that of control young rats in ICSS (current intensity, bar press rates), DMT and RRPST. However, treatment with red ginseng significantly ameliorated place-navigation learning deficits in aged rats in the PLT. Similarly, red ginseng ameliorated learning and memory deficits in young rats with hippocampal lesions in the same tasks. In the neurophysiological study using young rats, perfusion of hippocampal slices with non-sapon in fraction of red ginseng significantly enhanced magnitudes of the long-term potentiation (LfP) in the CA3 subfield. In the pharmacological study, treatment with red ginseng did not affect ChAT activity in aged rat brain including the hippocampal formation. These results strongly suggest that red ginseng ameliorates learning and memory deficits in aged rats through actions on the CA3 subfield of the hippocampal formation, which were independent of the presynaptic components of the cholinergic system

Primary neuronal culture was studied for observing effect of ginsenoside Rgl (Rgl) on serum-free medium induced apoptosis. Results showed that Rgl at concentration of 1 umol$.$ L-1 and 10 umol$.$L-1 could inhibit apoptosis, decrease intracellular calcium concentration in cultured cortical neurons, enhance SOD activity in both aged rat cortex and cultured cortical neurons, scavenge cytotoxic oxygen free radicals, decrease NO content and NOS activity in aged rat cortex and cultured cortical neurons, increase bel-2 gene expression in rat brain. These results provided new data for elucidating the anti-aging effect of Rgi. Rgl is considered to be a useful drug for treatment of Alzheimer's disease and brain aging.

Ginseng root has been considered to prevent neuronal degeneration associated with brain ischemia, but experimental proof in support of this speculation is limited. Moreover, few studies have compared the neuroprotective actions of ginseng ingredients with those of peptide growth factors and cytokines isf vivo. Using a gerbil forebrain ischemia model, we demonstrated that the oral administration of red ginseng powder before an ischemic insult prevents delayed neuronal death in the hippocampal CAI field and that a neuroprotective molecule within red ginseng powder is ginsenoside Rbl. The neurotrophic effect of ginsenoside Rbl, when examined in the gerbil ischemia model and in neuronal cultures was as potent as or more potent than the effects of epidermal growth factor, ciliary neurotrophic factor, erythropoietin, prosaposin, interleukin-6 and interleukin-3. Besides the protection of hippocampal CAI neurons against brain ischemia/repercussion injuries, ginsenoside Rbl was shown to prevent place navigation disability, cortical infarction and secondary thalamic degeneration in stroke-prone spontaneous hypertensive rats with permanent occlusion of the unilateral middle cerebral artery distal to the striate branches. These findings may validate the empirical use of ginseng root for the treatment of cerebrovascular diseases

We have investigated the antinociceptive efficacy of ginseng saponins in mice using l% formalin, which induce two phases of pain (acute and tonic pains) and is known to induce a clinically related pain. Ginseng total saponins (GTS) relieved both phases of pain with EDso of 162 mghg for acute and 92 mg/kg for tonic pain, respectively. Both protopanaxadiol (PD) and protopanaxatriol (PT) saponins did not attenuated acute phase of pain but relieved tonic phase of pain with EDso of 45 mg/kg for PD saponins and 105 mghg for PT saponins, respectively. Moreover, ginsenoside Rc, Rd, and Re among representative ginsenosides such as Rbl, Rc, Rd, Re and Rgl relieved slightly but significantly acute phase of pain and strongly attenuated tonic phase of pain but Rf relieved only tonic phase of pain. However, PD and PT saponins, and the individual ginsenosides tested except GTS did not greatly attenuate thermal noxious pain (tail-flick test). These results suggest that single ginsenoside or mixture of various ginsenosides mainly induce differential antinociception in mice.

We investigated the influence of the root of Panax ginseng C. A. Meyer on the secretion of catecholamines from bovine adrenal chromaffin cells, which are used as a model of nervous systems. In two major parts extracted from the ginseng root, the crude saponin fraction, but not the non-saponin fraction, reduced the secretion from the cells, stimulated by acetylcholine (ACh). Ginseng saponins (ginsenosides) are classified into three groups, the panaxadiol, the panaxatriol and the oleanolic acid groups, on the basis of the chemical structures of their saponins. Both the panaxadiol and the panaxatriol saponins, excluding only one oleanolic acid saponin ginsenoside-Ro, generally reduced the ACh-evoked secretion. The inhibitory effects of the panaxatriol were much stronger than those of the panaxadiol. However, ginsenoside-Rg, and -Rh3 in the panaxadiol saponins were the potent inhibitors comparable to the panaxatriol saponins. Ginsenoside-Rg2 in the panaxatriol was the most effective. It is probable that the ginsenoside inhibition of the catecholamine secretion is due to the suppression of the function of the nicotinic ACh receptor-cation channels. On the other hand, ginsenoside-Rg2 did not affect the angiotensin II-, the bradykinin-, the histamine- and the neurotensin- induced catecholamine secretions from the chromaffin cells and the muscarine- and the histamine- induced contraction of the ileum in guinea-pigs. Ginsenoside-Rbl, a panaxadiol saponin, and ginsenoside-Ro had no or only a slight effect on them. On the contrary, ginsenoside-Rg3 not only competitively inhibited the muscarine-induced ileum contraction but also reduced the angiotensin R -, the bradykinin-, the histamine- and the neurotensin-induced catecholamine secretions. Thus, the ginseng root contains active ingredients, namely some ginsensides, which suppress the responses induced by receptor stimulation. The inhibitory effects of ginseng saponins may be one of the action mechanisms for the pharmacological effects of the Panax ginseng root.

In the present study, we assayed a number of compounds isolated from Panax ginseng C. A. Meyer (Araliaceae) for an ability to protect rat cortical cell cultures from the deleterious effects of the neurotoxicant, glutamate. We found that ginsenosides Rbl and Rg3 significantly attenuated glutamate-induced neurotoxicity. Brief exposure of cultures to excess glutamate caused extensive neuronal death. Glutamate-induced neuronal cell damage was significantly reduced by pretreatment with Rbl and Rgl. Ginsenosides Rbl and Rg3 inhibited the overproduction of nitric oxide which routinely follows glutamate neurotoxicity and preserved the level of superoxide dismutase in glutamate-treated cells. Furthermore, in cultures treated with glutamate, these ginsenosides inhibited the formation of malondialdehyde, a compound produced during lipid peroxidation, and diminished the influx of calcium. These results show that ginsenosides Rbl and Rg1 exerted significant neuroprotective effects on cultured cortical cells. As such, these compounds may be efficacious in protecting neurons from oxidative damage produced by exposure to excess glutamate.

We hypothesized the primary effect of ginseng was to protect cell membrane fatty acids from decomposition caused by free radicals. To confirm the antioxidant effect of ginseng, we measured the inhibitory effect on the formation of thiobarbituric acid-reactive substances, an indicator of lipid peroxidation, and evaluated the free radical scavenging effect of ginseng by electron spin resonance spectrometer, and gas chromatography. The results showed that thiobarbituric acid-reactive substances formed and the loss of arachidonic acid during lipid peroxidation, and that hydroxyl (-like) radical peak formed by the iron complex (ferric nitrilotriacetate, an known free radical generator in vitro) were completely inhibited by ginseng extract. This antioxidant effect of ginseng may be responsible for its wide pharmacological actions in clinical practice. As the free radical reactions in general are rapid and non-specific, ginseng seems to act as a normalizer, rather than a general tonic, at the stages of acute or chronic active phase of the various diseases.

Superoxide dismutase (SOD) and catalase constitute the first coordinated unit of defense against reactive oxygen species. Here, we examined the effect of ginseng saponins on the induction of SOD and catalase gene expression. To explore this possibility, the upstream regulatory promoter region of Cu/Zn superoxide dismutase (SODI) and catalase genes were linked to the chloramphenicol acetyl-transferase (CATI structural gene and introduced into human hepatoma HepG2 cells. Total saponin and panaxatriol did not activate the transcription of SODI and catalase genes but panaxadiol increased the transcription of these genes about 2-3 fold. Among the Panaxadiol ginsenosides, the Rb2 subtraction appeared to is a major induce of SODI and catalase genes. Using the deletion analyses and mobility shift assays, we showed that the 5051 gene was greatly activated by ginsenoside Rba through transcription factor AP2 binding sites and its induction. We also examined the effect of the content ratio of panaxadiol extracted from various compartment of ginseng on the transcription of 5031 gene. Saponin extract that contains 2.6-fold more PD than PT from the fine root Increased the SODI induction about 3-fold. These results suggest that the panaxadiol fraction and its ginsenosides could induce the antioxidant enzymes, which are important for maintaining cell viability by lowering level of oxygen radical generated from intracellular metabolism.

The first original inducer of interferon had been synthesized in Russia in 1965-1967. It was 2-car-boxiethyl-germanysesquioxan (Lx-13) and other-1 hydroxigermanytrans-monohydral (Lx-5), These compounds have very high induct$\circledcirc$on of interferon. The strain of Panax ginseng C. A. Meyer was recultivated on medium with different concentiation of (Lx-13) and (Lx-5) many times. The strain was stabilized when biomass of cells contain of the Ge form 10${\times}$10-3mg% to 2.3x10-3mg% to ashes, Biomass are hard physical work (swimming test) and also had stress-protective, immunomodulating action and anticarcinogenic effect hampered the sarcoma-180 by 33-80% and suppressed quantity of metanes on 43-46%.

Ginseng total saponins (GTS) injected intracerebroventricularly (i.c.v.) at doses from 0.1-1 vs inhibited the i.c.v. injection stress-induced plasma corticosterone levels in mice. The inhibitory action of GTS was blocked by co-administered NG-nitro-L-arginine methyl ester (L-NAME; 1.5 us, i.c.v.), an. inhibitor of nitric oxide synthase (NOS). Of the ginsenosides Rbl, Rba, Rc, Rd, Re, Rf, Rgl,20(S)-Rg3, and 20(R)-Rg3 injected i.c.v. at doses from 0.01 to 0.3ug(or 1 uE),20(5)-Rg3 and Rc significantly inhibited the o.c.v. injection stress-induced Plasma corticosterone levels. The inhibitory actions of 20(S)-Rg3 and Rc were blocked by co-administered L-NAME (1.5 n, i.c.v.). These results suggest that G75, 20(S)-Rg3 and Rc may inhibit the i.c.v. injection stress-induced hypothalamo-pituitary-adrenal response by inducing NO production in the brain.

Symbiotic associations between land plants and fungi have been known for more than one hundred years. Vesiculararbuscular mycorrhizas (VAM) are the most common symbiosis in flowering plants and can be recognized in almost all plant families. These fungal associations play a very important role in the growth and survival of plant species. However, with respect to the importance and intensity of the VAM, there is great variation among host species. Our knowledge of the VAM fungus-plant association in Araliaceae is very limited. After the first reports of the occurence of VAM in lateral roots of Panax species, mycorrhizal structures are now described as special structures representing the so-called Paris type. In this type, the development of new spores and vesicles is extremely low. This and the type of colonization of the fungus in Panax roots indicates on, one hand, the high intensity of the VAM and, on the other hand, a remarkable dependency for VAM in members of the Panax species. Therefore, it can be easily understood that cultivated Panax plants exhibit a significant uptake of nutrients and this leads to an extremely depleted soil at harvest. Further, the soil is nearly free of the spores of VAM fungi as they germinate each year on the newly developing Panax roots.

A lot of individual ginseng plants were selected in the farmer's fields to develop new ginseng varieties with desirable traits. Among them, a promising line has been developed through comparative cultivation of several lines selected with pure line separation of local raced. It was then designated as "KC (denotes Korean Ginseng)" and tested in the regional yield and adaptation trials for 10 years. KG lines grew vigorously after 4 years of age. Especially, KG 102 line arson운 them showed traits of multiple and short stems. As for the root characters, the length of taproot of KG 101 line was longer than that of local race, Jakyung-jong, or other lines ailed the root weight of KG 102 line waIn 15 % higher than that of local race. In general, KG 101, KG 103, KG 104, and Hwangsauk-jong had good root shape. Total amount of ginsenosides of ginseng taproot was the highest in KG 103 line than in local race and other lines. In these studies, we, elected three superior lines, KG 101, KG 102, and KG 103, having characteristic of good root shape, high yield, and large amount of ginsenoside, respectively.

The Canadian production of American ginseng (Panax quinquefolius L.) occurs mainly in Ontario, British Columbia and the Atlantic provinces. Although ginseng is a profitable crop, its successful production is dependent on careful consideration of cultural management f include site selection, site preparation, seed selection and handling, shading actors which and mulching, pest and nutritional management, and handling of harvested crops. Diseases of particular concern in Atlantic Canada are root rots caused by Phytopkthora cactorum, Cylindrocarpon destructans and Fusarium sp. Recently two systemic fungicides (metalaxyl and fosetylal) were registered; however, growers in Atlantic Canada have experienced metalaxyl resistance resulting from the reliance on this single compound for the control of Phytophthora sap. Current research being conducted on alternative control of these diseases will be discussed. In weed control research, 2, 4-D, MCPA, clopyralid have continued to show promise for weed contro1 at low rates. In trials to evaluate non-selective herbicides as post-senescence or pre-emergence in ginseng, glyphosate (Round-up) provided control of perennials as well as willowherb and lambsquarters. In phytoxicity trials, ginseng significantly tolerated grass herbicides, including clethodim, rimsulfuron, trakloxydim, nicosulfuron and fenoxyprop. For broadleaf herbicides, significant tolerance was shown for bromoxynil, thifensulfuron methyl, flumetulam/clopyralid, thifensulfuro/tribenuron. Disease and weed management of ginseng in Atlantic Canada will be discussed.

The northeast of China is the main productive area of wild ginseng, including Changbai Mountains the south of Little Xingan Mountains, Wanda Mountains and Zahang Guangcai Mountains. The author has been oberving the ecological environment of ginseng in more than 20 sites for 20 years and obtains a great deal of ecological environment data about the growth and development of ginseng. This research can provide theoretical basis for the development of ginseng culture and the protection of ginseng resource.

Four new dammarnae-glycosides named ginsenosides Rgs, Rh4, RsB and Rf2 have been isolated 1'rom Korean red ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae) and their chemical structures have been elucidated by chemical and spectroscopic methods, including'H-'H COSY, HMQC, HMBC, NOESY, as 3-0- [$\beta$-D-glucopyranosyl(1 ~2)-$\beta$-D-glucopyranosyl] dammar-20(22) , B4-diene-3P,12P-diol (ginsenoside Rgs),6-0-$\beta$-D-glucopyranosyl-dammar-20(22),24-diene-3P,6P, 12P-triol (ginsenoside Rh4),3-0- [6" -0-acetyl-D-glucopyranosyl(1 ~2)--D-glucopyranosyl] 20(5)- protopanaxadiol (ginsenoside Rs3) and 6-0- [u-L-rhamno-pyranosyl(1 ~2)-$\beta$-D-glucopyranosyl] dammarane -3$\beta$, 6a, 12 $\beta$, 20(R),25-pentol(ginsenoslde Rfa). The absolute stereo structure of a double bond at C-20(22) was determined as entgegen type by applying NOESY.OESY.

From the underground part of Panax vietnamensis Ha et Grushv., commonly known as Vietnamese ginseng, 50 triterpene glycosides including 24 new dammarane saponins named visa-ginsenosides-Rl-24 were isolated and identified. The structure of the new saponins was elucidated based on chemical and spectroscopic evidence. The saponin composition of Vietnamese ginseng is almost similar to that of ginseng (Panax ginseng C.A. Meyer) and other cultivated Panax spp. However, the content of ocotillos-type saponins, especially that of the major saponin, majonoside-R2 (5.29% yield), was surprisingly very high. The pharmacological activities of Vietnamese ginseng are essentially similar to those of ginseng. In addition, it has marked antibacterial activity against pathogenic Streptococcus app. and is effective in treatment of granular angina. The chemical composition and pharmacological activities have made Vietnamese ginseng an interesting member of Panax spp. from chemotaxonomical and pharmacological points of view,

A validated and reproducible HPLC method was developed for the profiling and quantitative analysis of ginsenosides in commercial products available in North America. Analysis of 280 Panax ginseng and Panax quinquefolius products showed profiles indicative of the presence of ginsenosides in the majority of these products. However, the quantitative contents of the products vary greatly, not only in products of different formulations, but also of products within each of the fromulations examined.

A new processed ginseng with fortified activity is developed. The process comprise with the heat treatment of fresh or white ginseng at higher temperature and pressure than those used for the preparation of red ginseng. This new processed ginseng showed 7 times higher antioxidant activity and more than 30 times stronger vasodilating activity than those shown in raw ginseng. Other activities found in the new processed ginseng include cancer chemoprevention, antinephrotoxic, and antineurotoxic activities. Less polar ginsenosides isolated from processed ginseng exhibited anti-platelet aggregation activity and anti-cancer activity. Many ginsenosides were isolated from this new processed ginseng, namely 20(S)-$Rg_3$,20(R)-$Rg_3$, $Rg_5$, $Rg_6$, $F_4$, $Rh_4$,20(S)-$Rg_3$,20(R)-$Rg_3$ and $Rg_4$. In addition to these known compounds, seven new ginsenosides, named as gisenoside $Rk_1$, $Rk_2$, $Rk_3$, $Rs_4$, $Rs_5$, $Rs_6$, and $Rs_7$ were isolated. The major constituents of new processed ginseng were 20(S)-$Rg_3$,20(R)-$Rg_3$, $Rk_1$ and $Rg_5$ which are minors in red ginseng. Since the chemical constituents and biological activities of this new processed ginseng are quite different from those of white or red ginseng, we designated it as $'$sun ginseng (仙蔘)$'$.s;$.

Chemical studies of nitrogen compounds of Panax ginseng seem relatively rare, Probably due to the isolation difficulties, subsequently the investigations of biological activities are little. The experimental conditions were established for highly complete extraction of peptides (basic, acidic and neutral) from Panax ginseng. This task was achieved by applying the follow isolation procedure: 1 , the sequential extraction with water, 0.1% TFA in 20% acetonitril and buffer pH 6.5 (water-pyridine-acetic acid 100:3:900) : 2, fractionation by ultrafiltration : 3, n-butanol extraction 4, cation- and anion-exchange chromatography : 5, chromato-electrophoresis. The comparison of red ginseng (xylem Sl pith part) and red ginseng inside white (xylem Sc pith part) was also provided. To analyze the peptide mixture the chromato-electrophoresis method of separation was applied. Optimal conditions for peptides mapping of sample were explored. Our experiments revealed the quantitative difference of peptide between xylem & pith and phloem & cortex part. We have also found the qualitative difference in the composition of polypeptides between normal red ginseng (xylem Sc pith part) and red ginseng inside-white (xylem St pith part)

A single administration of cocaine (CO), morphine (MOR) and methamphetamine (MA) showed hyperactivity in mice. Ginseng total saponin (GTS), ginsenosides Rbl and Rgl inhibited the hyperactivity induced by the drugs. The repeated administration of CO, MOR and MA showed the development of psychological dependence showing a.: the development of conditioned place preference (CPP) in mice and the development of dopamine (DA) receptor supersensitivity showing as sensitization of the drugs. GTS and Rgl inhibited the development of not only psychological dependence but also of DA receptor supersensitivity induced by CO and MA Rbl prevented also the development of psychological dependence and DA receptor supersensitivity induced by CO and MA but not by MOR. These results suggest that the development psychological dependence induced by the drugs is closely related with the development of DA receptor supersensitivity since both phenomena were inhibited by them. Apomorphine induced climbing behavior was also inhibited by G75 but not by both of Rbl and Rgl, indicating that GTS modulate dopaminergic action at both of pre and postsynaptic sites, but both of Rbl and Rgl , only at the presynaptic site. These results suggest that active components acting at the postsynaptic site exist in GTS. In this study, it was found that GTS, ginsenosides Rbl and Rgl inhibited tyrosine hydroxylase (TH) and these components exerted inhibitory effects on both Cal' currents and $\Delta$ Cm in rat adrenal chromaffin cells. These results suggest that G75 and ginsenosides regulate catecholamine synthesis and secretion. Meanwhile, it has been demonstrated that Rbl, at high doses has more powerful inhibition of cartecholamine secretion at the presynaptic site than Rbl. Therefore, it was presumed that inhibition of morphine induced psychological dependence by Rgl, but not by Rbl results from differences in the extent of this inhibitory action on dopaminergic synthesis and secretion.

A prospective study was conducted to evaluate the preventive effect of Korean ginseng against cancer in the population residing ginseng cultivation area, Kangwha-eup from August 1987 to December 1997. The participants consisted of 4,553 adults over 40 years old who completed a questionare on ginseng intake. During the surveillance period, 14.4% (656 of 4,553) of subjects had died, cancer accounting for 23.9% (157) of total deaths. The proportional hazard model of Cox was used to estimate relative risks when controlling simultaneously for covariates. Ginseng intakers had a decreased risk (relative risk(RR) =0.48, 95% confidence interval (Cl) : 0.34-0.66) for cancer compared with non-intakers. The RRs of cancer were 0.36 (95% Cl: 0.24-0.56) for multiple combination intakers. Among 24 red ginseng intakers, there were no cancer deaths. The RRs of ginseng intakers were 0.38 (95% Cl: 0.20-0.71) in gastric cancer and 0.29 (95% Cl: 0.15- 0.57) in lung cancer. These findings strongly suggested Korean ginseng have non-organ specific cancer preventive effects against cancer. Further research for clarifying the mechanisms of prevention and clinical trials on Korean ginseng must be conducted with worldwide collaborations

Administration of ginsenosides, a mixture of saponin extracted from Panax ginseng, decreased blood pressure in rat. Previous studies have shown that ginsenosides caused endothelium-dependent relaxation, which was associated with the formation of cyclic GMP, suggested that ginsenosides caused release of nitric oxide (NO) from the vascular endothelium. The aim of the present study was to characterize the endothelium-independent relaxation to ginsenosides in the isolated rat aorta. Ginsenosides caused a concentration-dependent relaxation of rat aortic rings without endothelium constricted with 25 mM KCI but affected only minimally those constricted with 60 mM KCI. Ginsenoside Rg3 (Rg3) was a more potent vasorelaxing agonist than total ginsenoside mixture and also the ginsenoside PPT and PPD groups. Relaxation to ginsenosides were markedly reduced by TEA, but not by glibenclamide. Rg3 significantly inhibited Cal'-induced concentration-contraction curves and the "50a2'influx in aortic rings incubated in 25 mM KCI whereas those responses were not affected in 60 mM KCI. Rg3 caused efflux of $"Rb in aortic rings that was inhibited by tetraethy- lammonium (TEA), an inhibitor of Ca"-dependent K'channels, but not by glibenclamide, an inhibitor of AfP-dependent K'channels. These findings indicate that ginsenosides may induce vasorelaxation via activation of Ca2'-dependent K'channels resulting in hyperpolarization of the vas- cular smooth muscle with subsequent inhibition of the opening of voltage-dependent Caf'channels. These effects could contribute to explain the red ginseng-associated vasodilation and the beneficial effect on the cardiovascular system.

1 . Experimental study Preventive effect of Korea Red Ginseng (KPG) on hypertensive retinal arteriolosis in rabbits was studied. The results as follows: Blood pressure: Hypertensive group (B) was obviously raised up in comparing with that in normal group(A) and in hypertension + KRG group(C). Ocular fundus:Changes in B group including the retinal arteriospasm, crossing arterioveous, exudation and edema. But C group showed lightly. Light microscope: HE stained vascular damage in retina including thickness hyalimisation, execdates and edema Electron microscope: The endothelial cells were arranged irregularly, different shape and showed cytoplasm loose and vacuole. Immunohistochemistry: Ginseng can regulating endothelin-1, angiotension-ll, endothelium grow factor expre,j,iion and secreation in retinal blood clrultion. 2. ClinicAl Study 66 of hypertensive patients (42 men, 23 women,48-68 years old)and 20 normal person (7 men, 13 women,47-68 years old) were administrated(p.0.) by HRG (3g per day for 6 weeks). The results showed that marked effective rate and total effective rate were 53cyo and 60.6alo respectively and no severe side effects were found. The above results suggest that Ginseng have a difinite hypotensive effect and a role of preventing hyperfine sloe arteriosclerosis.

Ginseng saponin (G5) purified from Panax ginseng, increase renal blood flow in rats. Nitric oxide (NO) is thought to be a substance endogenously released by G5 in preconstricted lungs and cultured endothelial cells. The present study aims to determine whether G5 could stimulate endogenous 1'elease of NO in rat kidney and urine levels of the stable NO metabolites, nitrite (NO,) and nitrate (NO,) and urinary COMP levels were measured 8 hr after a single intraperitoneal injection of GS (200 mg/kg) Into rats. The effects of the WO synthesis inhibitor, Nu-nitro-L-arginine methyl ester, .1nd the NO precursor, L-arginine, on the G5-induced changes were also determined. The activity of NO synthase, as determined by conversion of ('"C)-L-arginine to ('"C)-L-citrulline, in whole kidney, glomeruli and cortical tubules were also investigated. A single injection of GS resulted in endogenous production of NO as reflected by increase in serum and urine levels of N021N03 and urinary cGMP levels, which were inhibited by the addition o ( N-nitro-L-arginine methyl ester and restored fly L-arginine. GS also stimulated the activity of NO synthase in whole kidney as well as glomeruli and cortical tubules, and Nu-nitro-L-arginine methyl tilter significantly prevented this increase. In conclusion, GS stimulates endogenous NO production and thus, may play a protective role 1 11 the kidney by modulating renal blood flow.

Ginseng has been used in maintaining physical vitality all over the East Asian countries and recently its metabolism and actions on neurologic, cardiovascular and endocrinologic systems are being elucidated. Korean red ginseng (KRG) has been used in various aliments, and to prove its efficacy icy erectile dysfunction an international study on Asians other than Korean was performed. Patients with borderline organic and psychogenic erectile dysfunction were included. KRG were given daily, and placebos were given as controls. Treatment lasted a total of 3 months. Surveys including libido, erectile potency, the sexual satisfactions were given. Serum testosterone and erectile function study were taken. Among the 23 patients with KRG, 18 patients were followed. Four had diabetes, 2 hypertension, 3 hyperchole, iterolemia, 1 low testosterone,4 psychogenic, and 4 idiopathic. In 10 patients with placebo, 7 were followed for more than three months. The clinical efficacy of KRG was 66.7% on objective Questionnaire and 72.2% on subjective analysis. When KRG were given, all parameters surveyed have shown improvements compared to the controls. Serum testosterone Bevels were normalized in 2 patients with KRG, whose serum testosterone levels were reduced from prestudy. When the erectile functions after audiovisual stimuli evaluated using Rigiscan in 6 patients with KRG,4 showed rigidity move than 70oyc. One patient reported constipation, and 2 gastric up-sets in the KRG group. In conclusion, KRG has beneficiary action on male erectile capabilities with minimal side effects. Thus KRG has been proven effective in Koreans, and a result on other Asians is pending. The exact action mechanism and the active ingredients in KRC need to be itudied.

Cyclic nucleotide phosphodiesterases (PDEs) represent the unique enzymatic system degrddinf cAMP and cGMP which play a major role in the regulation of cell physiology. To investigate a possible molecular mechanism of ginsenosides, their activities were evaluated on PDEs which are recently described is new therapeutic targets. PDEs are classified into 7 families according to their genes (PDEI to PDE7) and are differently distributed in tissues. The IC50 values of ginsenosides were determined on PDEI to PDE 5 chromatographically isolatetl from bovine aorta. The results show that total ginseng saponin extract preferentially inhibits PDE 1 and PDE4 at concentrations nearby 200 ug/ml. Protopanaxadiol (PPD) fraction acts preferentially on PDE4 with and IC50 value of 100 nlml and inhibits also PDEI and PDE5 at 14 to 2 fold higher concentrations, respectively. Protopanaxatriol (PPT) fraction preferentially inhibits PDE 1 with and IC50 value of 170 ug/ml. Compound Rgl, originated from PPT fraction, and RC3 (5) represent the most active compounds towards PDE 1 with IC50 values around 80 UM. However Rg3 (R), epimer of Rgl (5) has no effect on the various PDEs tested, excepted on PDE3 rich is sligthly sensitive Compound Rbl, originated from PPD, acts on both PDEI and PDE4. It if two fold less active than Rgl and Rg3 (5) on PDEI. Taken together, these results mainly suggest that PDEI and PDE4 inhibitions could be a molecular mechanism which would participate in ginsenoside mechanisms, especially the effect of PPD on blood vessel and on CNS.

This study showed the anti-invasive activity of ginseng components, panaxadiol (PD) and panamatrlol (PT) on the highly metastatic HT1080 human flbrosarcoma cell line. PD and PT reduced tumor cell invasion through a reconstitute basement membrane in the transwell chamber. A significant down regulation of MMP-9 by PD and PT was detected by northern blot analysis. However, MMP-2 was constantly expressed. Quantitative gelatin based zymography confirmed a marked reduced expression of MMP-9 but not MMP-2 in the treatment of PD and PT. Since the chemical structures of PD and PT are very similar to that of dexamethasone, a synthetic glucocorticoid, it was investigated whether PD and PT act through GR. Western blot analysis and immunocytochemistry showed that PD and PT increased the GR fraction in the nucleus. These results suggest that ursolic acid may induce repression of MMP-9 by stimulating the nuclear translocation of GR and hence inhibiting the activity of AP-1 to TPA-responsible element of MMP-9 promoter region. In conclusion, we suggest that CR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT 1080 cells.

In the present study, we provide evidence that ginsenoside $Rh_2$ (G-$Rh_2$) as well as staurosporine induces apoptosis of human hepatoma SK-HEP-1 cells by caspase 3-mediated processing of $p21^{WAFI/CIPI}$ in the early stage of apoptosls. Immunoblottings showed that G-$Rh_2$ as well as statrosporine induced the processing of caspase-3 to an active form, pl7. In stable Bcl-2 transfectants however, G-$Rh_2$ induced DNA fragmentation, while staurosporine did not. In the early stage of apoptosis, $p21^{WAFI/CIPI}$ was detected to undergo proteolytic processing specifically conducted by caspase-3. $p21^{WAFI/CIPI}$ translated in vitro was cleaved into a p14 fragment, when incubated with cell extracts obtained from either G-$Rh_2$- or staurosporine-treated cells. Cleavage was equally inhibited in both cases by adding Ac-DEVD-cho, a specific caspase-3 inhibitor, but not by Ac-YVkD-cho, a specific caspase-l inhibitor. Similarly, $p21^{WAFI/CIPI}$ was efficiently leaved by recombinant caspase-3 overexpressed in E. coli. Moreover, the endogenous $p21^{WAFI/CIPI}$ of untreated-cell extracts was also cleaved by recombinant caspase-3. Mutation analysis allowed identification of two caspase-3 cleavage sites, $DHVD^{112}$/L and $SMTD^{149}$/F, which are located within, or near the interaction domains for cyclins, Cdks, and PCNA. Taken together, these results show that G-$Rh_2$ as well as staurosporine increases caspase-3 activity, which in turn directly cleaves $p21^{WAFI/CIPI}$ resulting in elevation of Cdk kinase activity in the early stages of apoptosis. We propose that proteolytic cleavage of $p21^{WAFI/CIPI}$ is a functionally relevant event that allows unleashing the cyclin/Cdk activity from the inhibitor seen in the earlier stage of apoptosis, the event of which may be associated with the triggering mechanism for the execution of apoptosis.

Ginsenoside Rh, (G-Rh,) from Panax ginseng induced morphological features of apoptosis and DNA fragmentation as a biochemical marker of apoptosis confirmed by TUNEL reaction and agarose gel electrophoresis in human neuroblastoma SK-N-BE(2) and rat glioma C6Bu-1 cells During apoptosis by G-Rh2, protein kinase C (PKC) isoforms were analysed by immunoblotting. In SK-N-BE(2) cells, the levels of a, p and ${\gamma}$ subtypes were increased by undergoing apoptosis, while PKC e isoform increased early in treatment (3 h and 6 h). In addition, PKC s isoform gradually decreased during apoptosis by G-Rh2 and PKC $\theta$ isoform was detected in neither untreated- nor G-Rh1-treated SK-N-BE(2) cells (data not shown). However, no significant changes in the level of S and s isoforms were observed in C6Bu-1 cells undergoing apoptosis by G-Rh2. These results suggest that PKC subtypes may play differential roles in apoptotic signal pathways and their roles can be cell type-specific in apoptosis induced by G-Rh2.

Ochratoxin A (OA) is a potent mycotoxin causing considerable health hazard and economic loss- e,i. OA is of concern as it is hepato-nephrotoxic, mutagenic, and carcinogenic to a great variety of animals. LDso of crude OA was 8.5 mgf kg.b.w., i.p. The clinical symptoms, mortalities and necropsy were recorded in rats injected with OA (LD5o, i.p.) during 10 days of daily treatment. Ginseng treatments (20 mg 1 kg. b.w., i.p.) : before, mixed with, or after OA dose, completely prevented the mortality in rats. OA-treated animals showed microcytic normochromic anaemia, lucocytosis, hypoproteinaemia and elevation of serum ALT, AST, AP, urea, and creatinine values. These findings were declined near the normal levels when ginseng injected with OA. OA (115 LDso) induced chromosomal aberrations (65.66%) compared to the control. When ginseng given 10 min before OA injection, chromosomal aberrations were reduced to be 31.66% compared to OA-treated animals. In conclusion: ginseng has a protective effect against ochratoxicosis, it has anti-genotoxic activity and it can repair the chromosomal damage induced by ochratoxin A. Key words Ochratoxicosis, Chromosomal aberrations, Mycotoxins, Ochratoxin A, Korean gin sting, Protective effect of Panax ginseng, Rat

It is an established fact that most of the carcinogens implicate bay-region diol epoxides as the ultimate carcinogenic metabolites. These electrophiles react with nucleophilic sites in the cells to form abducts. It is the formation of carcinogenic-DNA adducts that is thought to initiate carcinogenesis. In our previous study we have reported chemopreventive property of Ginseng on 7,12-dimethylbenz (a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. In this study we have examined the effect on formation of DMBA-DNA adducts in rat hepatocytes pretreated with ginseng. Primary cultures of rat hepatocytes were used. The cells wets treated with ginseng for 24 hrs and then with DMBA (iOn) for 18 hrs. Cells were then harvested, their DNA was isolated and analyzed by P)2 labelling. A significant reduction in the levels of DMBA-DNA adduces (adducts/108 nucleotides) was observed in all cultures pretreated with ginseng. The viability of cells was not affected by pre-treatment with ginseng. Our finding suggests that ginseng block or suppresses the events associated with chemical carcinogenesis by inhibiting metabolic activation of the carcinogens.

Ginseng is one of the most widely used medicinal plants, particularly in East Asian countries. Certain fractions or purified ingredients of ginseng have been shown to exert inhibitory effects on growth of cancer cells in culture or on tumorigenesis in experimental animals. Moreover, a recent epidemiologic study reveals that ginseng intake is associated with a reduced risk for environmentally related cancers such as esophageal, gastric, colorectal, and pulmonary tumors. Heat treatment of Panax ginseng C. A. Meyer at the temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed ginseng (designated as'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in f Xl 74 supercoiled DNA Induced by UV photolysis of H2O2 and was also capable of scavenging superoxide generated in vitro by xanthine/xanthine oxidate or in differentiated human promyelocytic leukemia (HL-60) cells by the tumor promoter,12-0-tetvade- canoylphorbol-13-acetate (TPA). Since tumor promotion is closely linked to oxidative stress, we have determined possible anti-tumor promotional effects of NGMe on two-stage mouse skin tumorigenesis. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA significantly ameliorated skin papillomagenesi s initiated by 7,12-dimethylbenz (a) anthracene (DMBA).'Likewise, TPA-induced epidermal ornithine decarboxylase activity and elevation of tumor necrosis factor-a were suppressed signifies%fly by NGMe pretreatment. NGMe topically applied onto surface of hamster buccal pouch 10 min before each topical application of DMBA inhibited oral carcinogenesis by 76olo in terms of multiplicity. Taken together, these results suggest that processed Panax ginseng C. A. Meyer has potential cancer chemopreventive activities.

Ginseng saponin from different part of Ginseng and 7 kinds of ginsenosides effect on immnotuncition of young and old mice. There have up-regulation effect in vivo and in vitro experiments for low function of old mice, but not up-regulation effect at normal immuno-function of young mice. That means "Adaptogens" of Ginseng saponin. Not appositions effect at Pg1 and Rb1 and have find, that effect relations with molecular weight of ginsenosides.senosides.

In this present study, we investigated the effects of red ginseng extract and its active constituents - Rbl , Re, Rgl on cycloheximide (CXM)-induced amnesia in the passive avoidance task in rats. Red ginseng water extract at 0.05-0.5 g/kg could improve CXM-induced amnesia in rats, Furthermore, the recovery effect of Rbl at 10 mghg administered 30 min before training trial from CXM-induced amnesia was better than those of Rbl administered other time before or after training trial. Rbl at 0.001-0.1 mghg could significantly improve CXM-induced amnesia and at 1 mghg completely augmented, but at 10 mghg its improving effect slightly weakened. Rgl and Re at 0.3-10 mghg could significantly improve CXM-induced amnesia and Rgl at 10 mg/kg completely avgmented. On the other hand, Rbl at 10 mghg could prolong the step through latencies in the training trial. These results suggest the beneficial effect of red ginseng extract on CXM-induced amnesia in rats could mainly due to the contribution of its active constituents - Rbl, Re, Rgl. The improving effect of Rbl on CXM-induced amnesia was best among the three active constituents. But the reduction in the improving effect of Rbl at 10 mg/kg might be due to the decrease in motor activity and attention to the passive avoidance task.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most notorious toxic environmental pollutants, induces various toxic effects in many organs including testes and is regarded as an endocrine disruptor. Korean ginseng, on the other hand, has been well known for its preventive effects on lox- ins, diabetes melltus and hyperlipidemia. We investigated, histopathologically, the effect of Korean Red ginseng water extract (KR-WE) on guinea pig testes damaged by TCDD. Ninety guinea pigs were divided into 6 groups: normal control (NC) group received vehicle and saline; TCDD,1191kg b.w., was administered intraperitoneally to the single dose TCDD-treated (77) group; 100 mghg b.w.16 and 200mg1kg b.w./d KR-WE were injected intraperitoneally to the preventive groups (PIOO and P2OO, respectively) for 28 days from 1 week before TCDD injection, and to the therapeutic groups (CIOO and C2OO, respectively) for 14 days since 1 week after TCDD administration. Increment of body weight was retarded to a larger extent by TCDD. Moreover, body weight of the 77 group decreased significantly 7 days after TCDD exposure, while that of preventive groups kept increasing. Decrease in body weight was not observed in KR-WE-treated groups. Weight decrease in testes caused by TCDD was remarkably protected by KR-WE. Testicles in 77 group displayed decreased tubular size and maturation arrest at the primary or secondary spermatocyte stage. On the other hand, maturation arrest in germ cells by TCDD was improved in KR-WE treated groups. Almost complete protection of the testes was observed in PIOO and P2OO groups. In addition, the therapeutic effect was noticed in C 100 and C2OO groups. These results provided strong evidence that Korean Red ginseng might be a useful agent for the prevention and treatment of testicular damage induced by environmental pollutants.

We used the saponin Rgi extracted from Panax ginseng to study its effects on lymphocytes of 10 young and 19 elderly persons. The proliferate response of Iymphocytes cocultured for 72h with PHA and saponin was measured by using MTT method and the'H-TdR incorporation procedure. PHA and Rgl had stimulative effects on the phenotype of Iymphocytes (p<0.001). Rgl also increased the fluidity of lymphocyte membrane of the aged (p<0.001). The CD2s and CDfsRA positive cells of Iymphocytes in the elderly were lower than those of the young people,8.6clo $\pm$ 2.7olo vs 10.43% : 3.5%, 20.95% $\pm$ 15.5clQ vs 50.86% :4.3olo, respectively. More CDfsRO positive cell lymphocy populations were seen in the aged. The CEfsRO positive cells of the young people were 39.63% $\pm$ 3.2%. We discussed the cause of declined immune function of Lymphocytes of aged person and the mechanism of the effect of P. ginseng on Lymphocytes. Key words: Saponin, Lymphocytes, Aged person, Stimulatory effect, and Panax ginseng

In order to evaluate menopausal syndrome objectively, examinations were performed as follows: 1) Simplified Menopausal Index (SMI Koyama) and QOL questionnaire (Nagata) were examined subjectively. 2) Urine 17-KS-5 (S Nishikaze), 17-OHCS (OH) were examined objectively. 3) A mobile telemedical device with EKG and KSG was lent to Patients. The subjects were 48 menopausal patients who visited our university hospital as outpatients. According to the results of 5, OH, the subjects were divided into 4 Groups; Group I is high S & high OH, Group ll low S & low OH, Group 111 is low S & high OH, Group tl is high S & low OH. Group IH was the largest (64.6%), Group of was none. The subjects showed significantly lower QOL condition and higher score of SMI. In the QOL, questionnaire items of fixation to physical status (psychogenic reaction), sleep (insomnia), pain(chronic pain) were in common. In SMI, functional vascular symptoms were the largest number. On treatment, Group I was considered to have no need for supplementary agents, but anti-Oketsu agents was prescribed. For Group ll and in some supplementary agents such as red ginseng were prescribed, because they showed low 5. In conclusion, all the groups showed a sign- nificant improvement of QOL and SMI. Group I showed a decrease of OH, Group ll showed an increase of 5, Group In showed an increase of S and SIOH and a decrease of OH. These phenomena were considered prohomeostatic. In QOL, the items of chronic pain, insomnia and appetite were improved. In SMI, chillness, dyspnea, palpitation, pain and fatigability were improved. In mobile tole-medical device, abnormal findings were found in 88.2% of patients. General sdaptation syndrome (Selye, H.) is considered to adjust human life. Menopause is the transit period to exhausted stage in it. So its symptoms vary from person to person. In conclusion, 5 and OH are useful both for classification of menopausal syndrome and for determining treatments according to the classification