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PubMed2001

Effects of Korean red ginseng and its mixed prescription on the high molecular weight dextran-induced blood stasis in rats and human platelet aggregation.

This study was undertaken to evaluate the antithrombotic effects of Korean Red Ginseng (KRG) and its new prescription (KRGP) consisting of five herbs such as Korean red ginseng, Ganoderma, Cinnamomi Cortex, Glycyrrhizae Radix and Laminaria. In rats with blood stasis induced by high molecular weight dextran, KRG and KRGP significantly restored not only the number of platelets and fibrinogen, but also suppressed the fibrin degradation products (FDP) to normal range. In platelet aggregation assay with human platelet rich plasma (PRP), KRG and KRGP significantly inhibited thrombin and collagen-induced platelet aggregation. The IC(50) values of KRG and KRGP were >2 and 0.23+/-0.01 mg/ml for thrombin, 0.32+/-0.01 and 0.17+/-0.02 mg/ml for collagen and 0.72+/-0.25 and >2 mg/ml for ADP, respectively. In coagulation assay, KRG and KRGP significantly prolonged activated partial prothrombin time (APPT) and prothrombin time (PT) as compared with control data. KRGP was found to be more effective than KRG alone on antithrombotic activity. These results suggest that KRGP may exert its antithrombotic activity due to inhibition of platelet aggregation and coagulation activity more than KRG.

Animals↗
PubMed1998

Effects of ginseng total saponin on morphine-induced hyperactivity and conditioned place preference in mice.

A single or repeated administration of morphine in mice produced hyperactivity, conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor supersensitivity. The hyperactivity induced by morphine was evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP effects were evaluated assessing the increased time spent by the mice to morphine and the inhibition of CPP by the decreased time spent by the mice in the white compartment. Postsynaptic DA receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg, s.c.). The intraperitoneal injection of ginseng total saponin (GTS) from the root of Panax ginseng C.A. Meyer (Araliaceae), prior to and during the morphine treatment in mice inhibited morphine-induced hyperactivity and CPP. GTS inhibited the development of postsynaptic DA receptor supersensitivity. A single dose administration of GTS also inhibited apomorphine-induced climbing behavior, showing the antidopaminergic action of GTS at the postsynaptic DA receptor. These results suggest that the development of morphine-induced CPP may be associated with the enhanced DA receptor sensitivity and that GTS inhibition of the morphine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by morphine.

Animals↗
PubMed1999

Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise.

The effect of prolonged treatment with the standardized Panax ginseng extract G115 on the antioxidant capacity of the liver was investigated. For this purpose, rats that had received G115 orally at different doses for 3 months and untreated control rats were subjected to exhaustive exercise on a treadmill. A bell-shaped dose response on running time was obtained. The results showed that the administration of G115 significantly increases the hepatic glutathione peroxidase activity (GPX) and the reduced glutathione (GSH) levels in the liver, with a dose-dependent reduction of the thiobarbituric acid reactant substances (TBARS). After the exercise, there is reduced hepatic lipid peroxidation, as evidenced by the TBARS levels in both the controls and the treated animals. The GPX (glutathione peroxidase) and SOD (superoxide dismutase) activity are also significantly increased in the groups receiving G115, compared with the controls. The hepatic transaminase levels, ALT (Alanine-amino-transferase) and AST (Aspartate-amino-transferase), in the recuperation phase 48 h after the exercise, indicate a clear hepatoprotective effect related to the administration of the standardized Panax ginseng extract G115. At hepatic level, G115 increases the antioxidant capacity, with a marked reduction of the effects of the oxidative stress induced by the exhaustive exercise.

Animals↗
PubMed1999

Ginsenoside-Rs4, a new type of ginseng saponin concurrently induces apoptosis and selectively elevates protein levels of p53 and p21WAF1 in human hepatoma SK-HEP-1 cells.

In this paper, we present evidence that ginsenoside-Rs4 (G-Rs4; an acetylated analogue of ginsenoside-Rg5), a new ginseng saponin isolated from Panax ginseng C. A. Meyer, elevates protein levels of p53 and p21WAF1, which are associated with the induction of apoptosis in SK-HEP-1 cells. Flow cytometric analyses showed that G-Rs4 initially arrested the cell cycle at the G1/S boundary, but consequently induced apoptosis as evidenced by generating an apoptotic peak. The induction of apoptosis was confirmed by the results of DNA fragmentation assays and alterations in cell morphology after treatment of the cells with G-Rs4. Immunoblot assays showed that G-Rs4 significantly elevated protein levels of p53 and p21WAF1, concurrently with the downregulation of both cyclins E- and A-dependent kinase activities and induction of apoptosis. We suggest that G-Rs4 induces apoptosis, the effect of which is closely related to the downregulation of both cyclins E- and A-dependent kinase activity as a consequence of selectively elevating protein levels of p53 and p21WAF1 in SK-HEP-1 cells.

Apoptosis↗
PubMed2003

Effects of Panax ginseng extract on lipid metabolism in humans.

The purpose of this study was to examine the effects of Panax ginseng extract (PGE) on lipid metabolism in humans by measuring cholesterol, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and plasma MDA levels were decreased by administration of PGE for 8 weeks (6g per day), however, high density lipoprotein (HDL) was increased. Those results suggest that hypolipidemic effect of PGE is associated with a decrease in TC, TG, LDL, MDA levels and an increase in HDL. These findings support scientific claims that ginseng has the hypolipidemic potential. Administration of PGE increased SOD and CAT activities while decreased MDA level indicating that antioxidant potential of PGE might induce hypolipidemic effect as one of action mechanism.

Adult↗
PubMed2003

Phytochemistry of wild populations of Panax quinquefolius L. (North American ginseng).

A survey of the phytochemistry of Panax quinquefolius L. (North American ginseng) collected from wild populations in Ontario, Quebec, Maine, Vermont, and Wisconsin was undertaken. Reverse-phase HPLC was used to determine the natural variation of levels of ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd and their total in leaf, stem, and root of authentic wild-grown material. The totals in roots varied from 1 to 16%, with the greatest number of individual samples having 4-5% total ginsenosides. The lack of ginsenoside Rf in roots of authentic wild populations confirmed its status as a phytochemical marker differentiating American and Asian ginseng. Ten geographically isolated wild populations were collected, and several showed significant variation in the levels of major ginsenosides. There was no statistical difference in mean ginsenoside content between wild and cultivated P. quinquefolius roots at 4 years of age, suggesting there is no phytochemical justification for wild crafting. Baseline data on total ginsenoside levels for authentic wild P. quinquefolius reported here provide reference levels for quality assurance programs.

Canada↗
PubMed2005

Simplified extraction of ginsenosides from American ginseng (Panax quinquefolius L.) for high-performance liquid chromatography-ultraviolet analysis.

Four methods were tested for extraction and recovery of six major ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1) found in roots of American ginseng (Panax quinquefolius): method A, sonication in 100% methanol (MeOH) at room temperature (rt); method B, sonication in 70% aqueous MeOH at rt; method C, water extraction (90 degrees C) with gentle agitation; and method D, refluxing (60 degrees C) in 100% MeOH. After 0.5-1 h, the samples were filtered and analyzed by high-performance liquid chromatography (HPLC)-UV. A second extraction by methods C and D was done, but 85-90% of ginsenosides were obtained during the first extraction. Lyophilization of extracts did not influence ginsenoside recovery. Method D resulted in the highest significant recoveries of all ginsenosides, except Rg1. Method C was the next most effective method, while method A resulted in the lowest ginsenoside recoveries. Method B led to similar recoveries as method C. All methods used one filtration step, omitted time-consuming cleanup, but maintained clear peak resolution by HPLC, and can be used for quantitative screening of ginsenosides from roots and commercial ginseng preparations.

Chromatography, High Pressure Liquid↗
PubMed2006

Steamed American ginseng berry: ginsenoside analyses and anticancer activities.

This study was designed to determine the changes in saponin content in American ginseng berries after treatment by heating and to assess the anticancer effects of the extracts. After steaming treatment (100-120 degrees C for 1 h, and 120 degrees C for 0.5-4 h), the content of seven ginsenosides, Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd, decreased; the content of five ginsenosides, Rh1, Rg2, 20R-Rg2, Rg3, and Rh2, increased. Rg3, a previously identified anticancer ginsenoside, increased significantly. Two hours of steaming at 120 degrees C increased the content of ginsenoside Rg3 to a greater degree than other tested ginsenosides. When human colorectal cancer cells were treated with 0.5 mg/mL steamed berry extract (120 degrees C 2 h), the antiproliferation effects were 97.8% for HCT-116 and 99.6% for SW-480 cells. At the same treatment concentration, the effects of unsteamed berry extract were 34.1% for HCT-116 and 4.9% for SW-480 cells. After staining with Hoechst 33258, apoptotic cells increased significantly by treatment with steamed berry extract compared with unheated extracts. Induction of apoptosis activity was confirmed by flow cytometry after staining with annexin V/PI. The steaming of American ginseng berries augments ginsenoside Rg3 content and increases the antiproliferative effects on two human colorectal cancer cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Simultaneous quantification of ginsenosides in American ginseng (Panax quinquefolium) root powder by visible/near-infrared reflectance spectroscopy.

Near-infrared reflectance spectroscopy (NIRS) was examined as a possible alternative to high-performance liquid chromatography (HPLC) for the analysis of ginsenosides from American ginseng (Panax quinquefolium) root powder (n = 26). NIR spectra were collected over 400-2500 nm. For each sample and individual ginsenoside quantified by HPLC, spectral data were regressed against the chemical data to develop prediction equations. The spectral prediction equations produced high correlation coefficient (1-VR) values and low standard errors of cross validation (SECV) values for the determination of individual and total ginsenosides. The contents of individual ginsenosides, Rb(1), Rb(2), Rc, Rd, Re, Rg(1), Ro, m-Rb(1), m-Rb(2), m-Rc, m-Rd, and total ginsenosides (X +/- SECV) were (1.29+/-0.18)%, (0.273+/-0.096)%, (0.298+/-0.052)%, (0.091+/-0.027)%, (1. 015+/-0.114)%, (0.116+/-0.018)%, (0.25+/-0.040)%, (0.776+/-0.116)%, (0.197+/-0.074)%, (0.239+/-0.083)%, (0.143+/-0.042)%, and (4.393+/-0.283)%, respectively. The (1-VR) values of cross validation were 0.877, 0.872, 0.955, 0.834, 0.899, 0.919, 0.325, 0.849, 0.902, 0.877, 0.871, and 0.963, respectively. Results indicated that the NIRS method could be used for the analysis of the major ginsenosides, Rb(1), Re, and m-Rb(1), as well as the total ginsenosides in American ginseng.

Calibration↗
PubMed2001

A novel activation of Ca(2+)-activated Cl(-) channel in Xenopus oocytes by Ginseng saponins: evidence for the involvement of phospholipase C and intracellular Ca(2+) mobilization.

1. The signal transduction mechanism of ginsenosides, the active ingredients of ginseng, was studied in Xenopus oocytes using two-electrode voltage-clamp technique. Ginseng total saponin (GTS), i.e., an unfractionated mixture of ginsenosides produced a large outward current at membrane potentials more positive than -20 mV when it was applied to the exterior of oocytes, but not when injected intracellularly. The effect of GTS was concentration-dependent (EC(50): 4.4 microg ml(-1)) and reversible. 2. Certain fractionated ginsenosides (Rb(1), Rb(2), Rc, Rf, Rg(2) and Ro) also produced an outward current in a concentration-dependent manner with the order of potency of Rf>Ro>Rb(1)=Rb(2)>Rg(2)>Rc. Other ginsenosides (Rd, Re and Rg(1)) had little or no effect. 3. The GTS effect was completely blocked by bath application of the Ca(2+)-activated Cl(-) channel blocker niflumic acid and by intracellular injection of the calcium chelator BAPTA or the IP(3) receptor antagonist heparin. Also, the effect was partially blocked by bath-applied U-73122, a phospholipase C (PLC) inhibitor and by intracellularly injected GTP gamma S, a non-hydrolyzable GTP analogue. Whereas, it was not altered by pertussin toxin (PTX) pretreatment. 4. These results indicate that: (1) interaction of ginsenosides with membrane component(s) at the extracellular side leads to Ca(2+)-activated Cl(-) channel opening in Xenopus oocyte membrane; and (2) this process involves PLC activation, the release of Ca(2+) from the IP(3)-sensitive intracellular store and PTX-insensitive G protein activation.

Animals↗
PubMed2002

Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation.

The aim of the present research was conducted to elucidate anti-septicaemic effect of a polysaccharide (PS) isolated from Panax ginseng C.A. Meyer (Araliaceae) by nitric oxide production from stimulated macrophage. In vitro assays for the activity measurement of PS, NO production test with Greiss reagent, phagocytic activity test using zymosan and cytokines production test using ELISA kit were also conducted. In vivo anti-septicaemic activity was assessed by using C57BL/6J mice. This was done with Staphylococcus aureus infection test. PS used at 0.025 mg/kg concentration showed a potent anti-septicaemic activity (80%, survival). However, it did not directly inhibit S. aureus in a minimum inhibitory concentration (MIC) test, conducted in vitro (data not shown). Nitric oxide production via macrophage activation showed the highest value of 5.5 nmol/ml at 1 microg/ml PS. In in vitro phagocytic activity test, PS at 10 microg/ml concentration showed a potent phagocytic activity for zymosan with 167% of the control. Production of TNF-alpha by macrophage activation at 10 microg/ml of PS was 96% lysis of L929. Also production of IL-1 and IL-6 by stimulation of macrophage with 100 microg/ml PS dose increased to 235 pg/ml and 0.47 ng/ml, respectively. The low mortality of PS treated (0.025 mg/kg) infected mice was concurrent with decreased bacterial content in the blood. Nitric oxide production in S. aureus infected mice whose macrophage was stimulated by PS (0.025 mg/kg) increased approximately 4 times than the untreated S. aureus infected group at 24 and 48 h incubation. In the PS treated (0.025 mg/kg) group, the intracellular concentration of S. aureus in macrophages decreased approximately by 50%, compared with the untreated group. Combine treatment with PS (0.025 mg/kg body weight) and vancomycin (10 mg/kg B.W.) resulted in 100% survival of the animals, whereas only 67% or 50% of the animals survived, respectively, when treated with PS or vancomycin alone. These results suggest that PS from Panax ginseng possess a potent anti-septicaemic activity by stimulating macrophage and a potentiality as an immunomodulator against sepsis occurred by Staphylococcus aureus.

Animals↗
PubMed1999

Effects of a standardized Panax ginseng extract on the skeletal muscle of the rat: a comparative study in animals at rest and under exercise.

The effect of standardized Panax ginseng extract G115 on enzymatic activities, myotypological composition, capillaries and mitochondrial content was studied in the skeletal muscle of male rats Wistar. Simultaneously to the G115 administration the rats performed exercise. The animals were divided into 4 groups. The dose of the ginseng extract G115 was 50 mg/kg. The length of the experimental period was 12 weeks. After 24 hours of inactivity the muscles of the hindlimb were extracted. With regard to the enzymatic activities of the citrate synthase (CS) and lactate dehydrogenase (LDH), CS increases with exercise, while the LDH undergoes no major variations, either due to the exercise or the treatment. Treatment with G115 increases the capillary density and the mitochondrial content of the red gastrocnemius muscle. The results suggest that prolonged treatment with G115 increases the capillary density and the oxidative capacity of the muscles with greater aerobic potential in a manner similar to the performance of physical exercise. When exercise and treatment are combined, the effects that are obtained separately are not potentiated.

Animals↗
PubMed2001

Nitric oxide is involved in the immunomodulating activities of acidic polysaccharide from Panax ginseng.

The effects of an acidic polysaccharide isolated from the ethanol-insoluble and water-soluble fraction of Panax ginseng C. A. Meyer on immunomodulating activities were investigated. A high output nitric oxide synthase (iNOS) was shown in female BALB/c mice administered intraperitoneally with the acidic polysaccharide from ginseng. Newly synthesized iNOS protein was also observed in peritoneal macrophages cultured with interferon-gamma and the acidic polysaccharide. Spleen cells from acidic polysaccharide-treated mice did not proliferate in response to concanavalin A, but restored the responsiveness by the cotreatment of NG-monomethyl-L-arginine (NMMA) with concanavalin A. The treatment of mice with aminoguanidine, a specific iNOS inhibitor, alleviated the acidic polysaccharide-induced suppression of antibody response to sheep red blood cells. Present results suggest that the immunomodulating activities of the acidic polysaccharide were mediated by the production of nitric oxide.

Adjuvants, Immunologic↗
PubMed2001

Direct amplification of length polymorphism analysis differentiates Panax ginseng from P. quinquefolius.

The method of direct amplification of length polymorphism (DALP) was applied to authenticate Panax ginseng and P. quinquefolius. A 636-bp DALP fragment was present in all P. ginseng but absent in all the P. quinquefolius cultivars examined. We have shown that the use of DALP and conversion of specific polymorphic band to sequence-tagged site (STS) for quick authentication may be applied to authenticate related medicinal materials.

Base Sequence↗
PubMed2002

Ginsenosides from Panax ginseng differentially regulate lymphocyte proliferation.

We have examined the immunosuppressive effects of representative ginsenosides (Rb1, Rb2, Re and Rg1) from Panax ginseng C. A. Meyer on CD4+ and CD8+ lymphocyte proliferation. Ginsenosides differentially modulated lymphocyte proliferation induced by concanavalin A (Con A), lipopolysaccharide (LPS), phytohemaglutinin (PHA) and interleukin-2 (IL-2). Thus, Rb1 and Re significantly enhanced Con A-induced lymphocyte proliferation, whereas Rg1 did not affect the proliferation. Interestingly, however, Rb2 strongly blocked Con A, LPS and PHA-induced lymphocyte proliferation with the IC50 values of 21.8, 29.0 and 24.0 microM, respectively. Moreover, Rb2 inhibited Con A-stimulated IL-2 production with an IC 50 of 13.3 microM. In the IL-2-stimulated CD8+ T cell (CTLL-2) proliferation assay, Re and Rg1 showed strong suppressive effects with IC50 values of 57.5 and 64.7 microM, respectively. In contrast, neither Rb1 nor Rb2 did inhibit CTLL-2 cell proliferation at tested concentrations. These results suggest that ginsenosides from P. ginseng may modulate lymphocyte proliferation in a different manner.

Animals↗
PubMed2003

Antiallergic activity of ginseng and its ginsenosides.

In this study, we measured the antiallergic activities of ginsenosides isolated from the root of Panax ginseng ( Araliaceae), and of their metabolites, as produced by human intestinal bacteria. Compound K, which was identified as a main metabolite, had the most potent inhibitory activity on beta-hexosaminidase release from RBL-2H3 cells and on the PCA reaction. The inhibitory activity of compound K was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. This compound demonstrated a membrane stabilizing action on differential scanning calorimetry. However, compound K did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that the antiallergic action of compound K originates from its cell membrane stabilizing activity and that the ginsenosides of ginseng are prodrugs with extensive antiallergic properties. Abbreviations. compound K:20- O-beta- D-glucopyranosyl-20( S)-protopanaxadiol DNP:dinitrophenol DSCG:disodium cromoglycate DPPC:dipalmitoylphosphatidylcholine DPPH:1,1-diphenyl-2-picrylhydrazyl HSA:human serum albumin IC 50 :50% inhibitory concentration EC 50 :50% effective concentration XOD:xanthine oxidase ICR:Institute of Cancer Research PBS:phosphate buffered saline PCA:passive cutaneous anaphylaxis RAW264.7:mouse monocyte leukemiaRBL-2H3: rat basophil leukemia SD:Sprague-Dawley

Administration, Oral↗
PubMed2004

Species identification from Ginseng drugs by multiplex amplification refractory mutation system (MARMS).

The multiplex amplification refractory mutation system (MARMS) was applied to the identification of 5 Panax species ( P. ginseng, P. japonicus, P. quinquefolius, P. notoginseng and P. vietnamensis). A set of specific primers, including 2-pair primers on chloroplast trnK gene and nuclear 18S rRNA gene regions, respectively, was designed and synthesized for each species on the basis of species-specific sequences of the 2 genes. By using 5 sets of specific primers, in turn, PCR amplifications were performed with total DNA extracted from 5 Panax species as template under appropriate condition, and each resulting product was detected by agarose gel electrophoresis. The results showed that two expected fragments, one from trnK gene and another from 18S rRNA gene regions, were observed simultaneously only when the set of species-specific primers encountered template DNA of the corresponding species. This assay could give more reliable results for identification of not only 5 Panax species but also corresponding Ginseng drugs by simultaneous detection of 4-site nucleotide differences on 2 completely different genes.

DNA Mutational Analysis↗