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Korean red ginseng slows depletion of CD4 T cells in human immunodeficiency virus type 1-infected patients.

We have previously showed that long-term intake of Korean red ginseng (KRG) delayed disease progression in human immunodeficiency virus type 1 (HIV-1)-infected patients. In the present study, to investigate whether this slow progression was affected by KRG intake alone or in combination with HLA factor, we analyzed clinical data in 68 HIV-1-infected patients who lived for more than 5 years without antiretroviral therapy. The average KRG intake over 111.9 +/- 31.3 months was 4,082 +/- 3,928 g, and annual decrease in CD4 T cells was 35.0 +/- 28.7/microl. Data analysis showed that there are significant inverse correlations between the HLA prognostic score (0.29 +/- 1.19) and annual decrease in CD4 T cells (r = -0.347; P < 0.01) as well as between the amount of KRG intake and annual decrease in CD4 T cells (r = -0.379; P < 0.01). In addition, KRG intake significantly slowed the decrease in CD4 T cells even when influence of HLA class I was statistically eliminated (repeated-measure analysis of variance; P < 0.05). We also observed significant correlation between KRG intake and a decrease in serum-soluble CD8 antigen level (r = 0.62; P < 0.001). In conclusion, these data show that KRG intake independently and significantly affected the slow depletion of CD4 T cells irrespective of HLA class I.

CD4 Lymphocyte Count↗

Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy.

Rh2 is a ginsenoside extracted from ginseng that has drawn attention in a few laboratories in Asian countries because of its potential tumor-inhibitory effect. In the present study, we tested Rh2 on many tumor-cell lines for its effects on cell proliferation, induction of apoptosis, and potential interaction with conventional chemotherapy agents. Our results showed that Rh2 inhibited cell growth by G1 arrest at low concentrations and induced apoptosis at high concentrations in a variety of tumor-cell lines, possibly through activation of caspases. The growth arrest and apoptosis may be mediated by 2 separate mechanisms. Apoptosis is not dependent on expression of the wild-type p53 nor the caspase 3. In addition, the apoptosis induced by Rh2 was mediated through glucocorticoid receptors. Most interestingly, Rh2 can act either additively or synergistically with chemotherapy drugs on cancer cells. Particularly, it hypersensitized multidrug-resistant breast cancer cells to paclitaxel. These results suggest that Rh2 possesses strong tumor-inhibiting properties, and potentially can be used in treatments for multidrug-resistant cancers, especially when it is used in combination with conventional chemotherapy agents.

Animals↗

Behavioral effects of Ginkgo biloba L., Panax ginseng C.A. Mey. and Gincosan.

The behavioral effects of a standardized extract from Panax ginseng roots (G115), of a standardized extract from Ginkgo biloba leaves (GK501) and of their combination (PHL-00701) (Gincosan) were examined in experiments on rats with undisturbed memory and on rats with experimentally-impaired memory (by alcohol or by muscarinic- and dopamine-receptor antagonists), using methods for active avoidance (shuttle-box) and passive avoidance (step-down and step-through). On multiple administration G115, GK501 and PHL-00701 exerted favorable effects on learning and memory. These effects varied with the dose and administration schedules, with the rat strain and with the behavioral method. Based on earlier results, we discuss the role of changes in brain biogenic amines induced by the extracts in their mechanism of action. The present results allow for ranking G115, GK501 and their combination PHL-00701 (Gincosan) among cognition-enhancing (nootropic) drugs.

Animals↗

Pharmacological properties of N-095, a drug containing red ginseng, polygala root, saffron, antelope horn and aloe wood.

This study sought to establish a pharmacological profile for N-095, a crude drug containing red ginseng, polygala root, saffron, antelope horn and aloe wood. Our studies on rats and mice revealed a number of pharmacological properties of this novel drug. N-095 increased the forced swimming time in mice and prevented gastric ulcers in rats under restraint and water immersion stress conditions at 100 mg/kg or higher. It also prevented footpad swelling in rats treated with lambda-carrageenin and histamine-induced gastric ulcers in rats at 300 mg/kg or higher. Furthermore, N-095 augmented the sedative effect in mice induced by hexobarbital, which is characterized by a decreased spontaneous motor activity and a prolongation of sleeping time. N-095 also stimulated spontaneous contractility of the uterus in rats at 1000 mg/kg and 2000 mg/kg and prevented hemolysis of erythrocytes by heating. In contrast, N-095 had no effect on the respiratory or cardiovascular system or on water and electrolyte regulation in rats or mice. These results show that N-095 is a relatively safe drug for use as a nutrient or tonic.

Animals↗

Effects of ginsenoside Rg1 of Panax ginseng on mitosis in human blood lymphocytes in vitro.

The ginsenoside Rg1 extracted from the root of Panax ginseng can promote mitosis in cultured human lymphocytes activated by PHA or Con A. Its most effective concentrations are around 0.0003-0.0005 mg per ml of medium. Experiments show that it does not arrest the cells at any particular mitotic stage. It can also enhance the DNA synthesis in the activated lymphocytes. As a result of the increased number of the mitotic cells and enhanced DNA synthesis, the cell density is significantly increased in the Rg1-treated culture as compared with the control. However, in the absence of a mitogenic lectin Rg1 cannot restart the quinescent human lymphocytes to divide in vitro; therefore it is not mitogenic to resting cells. The possible action of Rg1 on activated human lymphocytes as well as its pharmacological significance are discussed.

Cell Count↗

Effects of ginsenosides Rg1 and Rb1 of Panax ginseng on mitosis in root tip cells of Allium cepa.

The effects of ginsenosides Rg1 and Rb1 of Panax ginseng on mitosis in the onion root tip cells as well as on the rate of DNA synthesis in onion seedlings were studied. Results obtained from the concentration and time course study in bulb and seeding root tip cells indicate that Rg1 promotes and Rb1 inhibits mitosis, both being dose-dependent. The promoting effect of Rg1 on the rate of DNA synthesis was observed at the peak hour which occurs at the same time as that of the control. Rb1 was found to shift the peak hour of DNA synthesis to a later period of the experiment. These results are in agreement with the results obtained from the study of the cell cycle by pulse labeling and autoradiography, which show that Rg1 shortens the mitotic cell cycle and S period while Rb1 lengthens them. They in turn increase and decrease the mitotic indices respectively.

DNA↗

Plasma lipid-lowering action of ginseng saponins and mechanism of the action.

Elevation of plasma levels of cholesterol and triglyceride was reduced by the intramuscular injection of ginseng principles fraction 4 (saponin content, ca. 1/2). The elimination of intraperitoneally injected 4-[14C]-cholesterol from plasma was accelerated by fraction 4 administration. Fecal excretion [14C]bile acids and [14C]sterols after intraperitoneal injection of 4-[14C]-cholesterol was significantly increased by fraction 4 administration.

Animals↗

Gut and brain effects of American ginseng root on brainstem neuronal activities in rats.

Brainstem neurons receiving subdiaphragmatic vagal inputs were recorded in an in vitro neonatal rat brainstem-gastric preparation. Aqueous extracts of American ginseng root (Panax quinquefolium L.) were applied to the gastric compartment or the brainstem compartment of the bath chamber to evaluate the peripheral gut and central brain effects of the extracts on brainstem unitary activity. After Panax quinquefolium L. application to the gastric or brainstem compartment, a concentration-related inhibition in neuronal discharge frequency in the brainstem unitary activity was observed, suggesting that Panax quinquefolium L. may play an important role in regulating the digestive process and modulating brain function. In this study, pharmacological effects of American-cultivated Panax quinquefolium L. and Chinese-cultivated Panax quinquefolium L. were also compared. Our results suggest that American-cultivated Panax quinquefolium L. possesses a significantly stronger gastric modulating effect on brain neuronal activity.

Animals↗

Orally administered Panax ginseng extract decreases platelet adhesiveness in 66% hepatectomized rats.

The effect of oral administration of Panax ginseng extract (GE) on platelet adhesiveness was examined in 66% hepatectomized rats. A significant decrease in platelet adhesiveness was obtained when 125 mg/kg/day GE was administered for 6 days before and after hepatectomy. The total cholesterol concentration in the serum was also decreased by GE administration. Food intake was unaffected by GE administration. Serum parameters indicating liver and kidney function were unchanged after GE administration except for lipid metabolic parameters. Because enhanced platelet adhesiveness and hyperlipidemia induces atherosclerosis, these results suggest that orally administered GE is capable of improving the atherosclerotic condition associated with hepatectomy.

Animals↗

Effects of ginseng radix on sugar absorption in the small intestine.

Ginseng radix (GR) is often used in traditional Japanese kampo medicine. We studied the effect of GR on glucose and maltose transport in rat and human duodenal mucosa by Ussing's method, and on smooth muscle movement in rat duodenal muscle by Magnus' method. GR inhibited absorption of glucose or maltose in rat and human duodenal mucosa, but increased duodenal muscle movement. It suggests that the inhibition of sugar absorption by GR is more dominant than enhancement of duodenal muscle movement by GR.

Adult↗

Cyclooxygenase-2 inhibits novel ginseng metabolite-mediated apoptosis.

Recently, a novel intestinal bacterial metabolite of ginseng protopanaxadiol saponins, i.e., 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), has been reported to induce apoptosis in a variety of cancer cells. Here we show a differential effect of IH-901 on several cell types. Exposure to IH-901 for 48 hours at a supposedly subapoptotic concentration of 40 mumol/L led to both apoptotic cell death and G1 arrest in Hep3B cells, but only resulted in G1 arrest in MDA-MB-231, Hs578T, and MKN28 cells. Additionally, the treatment of MDA-MB-231, but not of Hep3B, with IH-901 up-regulated cyclooxygenase-2 (COX-2) mRNA (2 hours) and protein (6 hours), and enhanced the production of prostaglandin E2. In MDA-MB-231 cells, IH-901 induced the sustained activation of extracellular signal-regulated kinase (ERK), whereas inhibition of mitogen-activated protein/ERK kinase blocked IH-901-mediated COX-2 induction and resulted in apoptosis, suggesting the involvement of an ERK-COX-2 pathway. Combined treatment with IH-901 and nonsteroidal anti-inflammatory drugs inhibited COX-2 enzyme and induced apoptosis in MDA-MB-231 and Hs578T cells. Adenovirus-mediated COX-2 small interfering RNAs also effectively inhibited COX-2 protein expression and enhanced IH-901-mediated apoptosis without inhibiting ERK 1/2 phosphorylation, thus providing direct evidence that COX-2 is an antiapoptotic molecule. Moreover, IH-901-mediated G1 arrest resulted from an increase in p27Kip1 mRNA and protein expression followed by a decrease in CDK2 kinase activity that was concurrent with the hypophosphorylation of Rb and p130. In conclusion, IH-901 induced both G1 arrest and apoptosis, and this apoptosis could be inhibited by COX-2 induction.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of the standardized Ginseng Extract G115 on the metabolism and electrical activity of the rabbit's brain.

The objective of this original investigation was to study the effect of the standardized Ginseng Extract G115 on the metabolic activity and ECoG of the rabbit's brain. The results showed significant increase of the glucose uptake with simultaneous significant reduction of the lactate, pyruvate and lactate/pyruvate ratio. These findings indicate shift of glucose utilization by the drug from anaerobic to the more economical pathway. G115 was also shown to produce a desynchronizing effect on the electrocorticogram (ECoG) which correlated well with the biochemical findings.

Animals↗

Immune system effects of echinacea, ginseng, and astragalus: a review.

Traditional herbal medicine provides several remedies for strengthening the body's resistance to illness through effects on immune system components. This review article examines 3 popular herbal immune stimulants that are often of interest to cancer patients. Echinacea, a native of North America, is widely used to prevent, or provide early treatment for, colds. Preclinical studies lend biological plausibility to the idea that echinacea works through immune mechanisms. Numerous clinical trials have been carried out on echinacea preparations: it appears that the extracts shorten the duration and severity of colds and other upper respiratory infections (URIs) when given as soon as symptoms become evident. However, trials of long-term use of echinacea as a preventive have not shown positive results. Ginseng has been studied in some depth as an antifatigue agent, but studies of immune mechanisms have not proceeded so far. Preclinical evidence shows some immune-stimulating activity. There have been several clinical trials in a variety of different diseases. Astragalus is the least-studied agent. There are some preclinical trials that show intriguing immune activity. The herbs discussed appear to have satisfactory safety profiles. Cancer patients may wish to use these botanicals to inhibit tumor growth or to boost resistance to infections. However, passive immunotherapy with herbs, with no mechanism to expose tumor antigens, is unlikely to be effective in inhibiting tumor growth. Although the margin of safety for these herbs is large, more research is needed to demonstrate the clear value of using herbs to improve resistance to infections.

Adjuvants, Immunologic↗

Ginsenoside-Rb1 from Panax ginseng C.A. Meyer activates estrogen receptor-alpha and -beta, independent of ligand binding.

We studied the estrogenic activity of a component of Panax ginseng, ginsenoside-Rb1. The activity of ginsenoside-Rb1 was characterized in a transient transfection system, using estrogen receptor isoforms and estrogen-responsive luciferase plasmids, in COS monkey kidney cells. Ginsenoside-Rb1 activated both alpha and beta estrogen receptors in a dose-dependent manner with maximal activity observed at 100 microm, the highest concentration examined. Activation was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that the effects were mediated through the estrogen receptor. Treatment with 17beta-estradiol or ginsenoside-Rb1 increased expression of the progesterone receptor, pS2, and estrogen receptor in MCF-7 cells and of AP-1-driven luciferase genes in COS cells. Although these data suggest that it is functionally very similar to 17beta-estradiol, ginsenoside-Rb1 failed to displace specific binding of [(3)H]17beta-estradiol from estrogen receptors in MCF-7 whole-cell ligand binding assays. Our results indicate that the estrogen-like activity of ginsenoside-Rb1 is independent of direct estrogen receptor association.

Animals↗

Immunomodulating activity of CVT-E002, a proprietary extract from North American ginseng (Panax quinquefolium).

The activity of CVT-E002, an aqueous extract containing mainly oligosaccharides and polysaccharides from North American ginseng (Panax quinquefolium), as an immunobooster on murine spleen cells and peritoneal macrophages, was studied in-vitro. CVT-E002 stimulated the proliferation of normal mouse spleen cells, of which the major responding subpopulation was identified as B lymphocytes. CVT-E002 also activated peritoneal exudate macrophages leading to enhanced interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production. In addition, CVT-E002 stimulated in-vivo immunoglobulin G (IgG) production in treated mice. These results identify some of the immunomodulating activities of CVT-E002 and suggest its use clinically for the modulation of immune responses.

Adjuvants, Immunologic↗

Pharmacological activity of sanchi ginseng (Panax notoginseng).

The pharmacological activity and constituents of the sanchi ginseng Panax notoginseng have been reviewed. The bulk of pharmacological findings have been based on the saponins or steryl glycosides, although polysaccharides with immunopotentiating activity, proteins with antifungal, ribonuclease and xylanase activity, and a triacylglycerol (trilinolein) with antioxidant activity have been reported. Protective actions against cerebral ischaemia, beneficial effects on the cardiovascular system, and haemostatic, antioxidant, hypolipidaemic, hepatoprotective, renoprotective and estrogen-like activities have been described. Various methods for authentication of P. notoginseng are available.

Animals↗

Characterization of two novel polysaccharides having immunological activities from the root of Panax ginseng.

Two acidic polysaccharides, called ginsenan S-IA and ginsenan S-IIA, were isolated from the root of Panax ginseng C. A. Meyer. They were homogeneous on electrophoresis and gel chromatography, and their molecular masses were estimated to be 5.6 x 10(4) and 1.0 x 10(5), respectively. Ginsenan S-IA is composed of L-arabinose: D-galactose: D-galacturonic acid in the molar ratio of 8:8:1, and ginsenan S-IIA is composed of L-arabinose: D-galactose: D-glucose: D-galacturonic acid in the molar ratio of 15:10:2:5, in addition to small amounts of O-acetyl groups. About a half (ginsenan S-IA) and about a quarter (ginsenan S-IIA) of the hexuronic acid residues exist as methyl esters. Reduction of carboxyl groups, methylation analysis, nuclear magnetic resonance and periodate oxidation studies indicated that their structural features include mainly alpha-1,5-linked L-arabino-beta-3,6-branched D-galactan type structural units. Both polysaccharides showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test and pronounced anti-complementary activity. These substances are the first examples having a relatively high content of both alpha-3,5-branched L-arabinose and beta-1,4-linked D-galactose units among the acidic arabinogalactans with activities on phagocytosis and anti-complement.

Arabinose↗