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Induction of nitric oxide synthase by saponins of heat-processed ginseng.

Total saponin of heat-processed ginseng (TSHG) stimulated the production of nitric oxide (NO) in interferon-gamma (IFN-gamma)-primed macrophages through the increased expression of inducible nitric oxide synthase (iNOS). However, TSHG by itself had a very weak effect on the NO synthesis without IFN-gamma priming. The saponins of white ginseng inhibited the NO production in lipopolysaccharide (LPS)/IFN-gamma activated macrophages rather than the stimulation of NO production found in IFN-gamma primed macrophages. The NO production by TSHG-stimulated macrophages was inhibited by the NOS inhibitor (N(G)-monomethyl-L-arginine (L-NMMA)) and nuclear factor-kappaB inhibitor (pyrrolidine dithiocarbamate (PDTC)). TSHG showed different serum-dependence from LPS on the activation of IFN-gamma primed macrophages. This property of TSHG may explain the intensified anti-tumor properties of heat-processed ginseng through its immunostimulating activity.

Animals↗

Mitogen-activated protein kinases mediate the oxidative burst and saponin synthesis induced by chitosan in cell cultures of Panax ginseng.

Chitosan (CHN) specially induced the activities of 39 kD and 42 kD protein kinases in ginseng cells, which could be suppressed by an inhibitor of mitogen-activated protein kinase (MAPK) pathway, PD98059. The immunoprecipitation (IP) using MAPK antibody or kinase assay in vitro also showed that CHN-induced 42 kD and 39 kD protein kinases belonged to the MAPK family. PD98059 suppressed CHN-induced transcriptions of ginseng squalene synthase and ginseng squalene epoxidase genes (gss and gse), CHN-induced accumulation of beta-Amyrin synthase (beta-AS) and synthesis of saponin. These results showed that CHN-induced activities of MAPKs were necessary for the CHN-induced saponin synthesis. EGTA and LaCl3 suppressed CHN-induced 39 kD and 42 kD MAPK activities. Ruthenium red (RR) could suppress CHN-induced 39 kD activity. All of them suppressed CHN-induced saponin synthesis. These results indicated that CHN-induced increment of cytosolic calcium was necessary for CHN-induced saponin synthesis. PD98059 also suppressed CHN-induced oxidative burst (including the increment of activity of plasma membrane NADPH oxidase and production of H2O2), but diphenylene iodonium (DPI), dimethylthiourea (DMTU) and 2,5-dihydroxycinnamic acid methyl ester (DHC) could not suppress CHN-induced MAPK activities, which indicated that MAPK was possibly function upstream of CHN-induced oxidative burst.

Cell Line↗

Assessment of various carbon sources and nutrient feeding strategies for Panax ginseng cell culture.

Ginseng (root of Panax ginseng C. A. Meyer) cells were cultivated on medium supplemented with various carbohydrates including sucrose, glucose, and fructose, at initial concentrations ranging from 10 to 110 g/L. Sucrose was shown to be the superior carbon source to the monosaccharides for ginseng cell growth and the optimal concentration was between 30 and 50 g/L. An increase in the initial concentration within this range increased the maximum cell density and growth index significantly, whereas much higher concentrations inhibited cell growth. Feeding of sucrose and some other medium components during the growth (fed-batch mode) was more effective in enhancing the cell growth and biomass productivity, increasing the growth index by more than 60-70% and biomass productivity by more than 50%.

Journal Article↗

Efficacy of polyphenon E, red ginseng, and rapamycin on benzo(a)pyrene-induced lung tumorigenesis in A/J mice.

The objective of this investigation was to determine the efficacy of several novel agents in preventing lung tumorigenesis in mice. We evaluated polyphenon E, red ginseng, and rapamycin in A/J mice treated with the tobacco-specific carcinogen benzo(a)pyrene for their ability to inhibit pulmonary adenoma formation and growth. We found that treatment with polyphenon E exhibited a significant reduction on both tumor multiplicity and tumor load (tumor multiplicity x tumor volume) in a dose-dependent fashion. Polyphenon E (2% wt/wt) in the diet reduced tumor multiplicity by 46% and tumor load by 94%. This result provided key evidence in support of a phase II clinical chemoprevention trial of lung cancer. Administration of red ginseng in drinking water decreased tumor multiplicity by 36% and tumor load by 70%. The mammalian target of rapamycin inhibitor rapamycin showed significant efficacy against lung tumor growth in the tumor progression protocol and reduced tumor load by 84%. The results of these investigations demonstrate that polyphenon E, red ginseng, and rapamycin significantly inhibit pulmonary adenoma formation and growth in A/J mice.

Adenoma↗

Determination of ginsenosides in Panax ginseng roots by liquid chromatography with evaporative light-scattering detection.

A liquid chromatographic method was developed and validated for the determination of ginsenosides in Panax ginseng roots by using evaporative light-scattering detection. Eighteen ginsenosides were separated on a reversed-phase C18 column with water-ammonium acetate-acetonitrile as the mobile phase. The method is suitable for the routine determination of ginsenosides in P. ginseng roots and extracts. The validation of the method was comprehensive for efficiency and recovery optimization of the P. ginseng roots extraction, specificity by liquid chromatography/mass spectrometry, linearity, stability, reproducibility, repeatability, intermediate precision, and robustness.

Chromatography, High Pressure Liquid↗

[Comparative effects of decreasing viscosity in different preparations of Chinese angelica root and ginseng].

OBJECTIVE: To compare the effects of different preparations of Chinese angilica root and ginseng on decreasing whole blood viscosity and plasma viscosity in rats. METHOD: The hemorheological method was used in vivo or in vitro and a Decreasing Viscosity Index (DIV) was defined as a comparative scalar. RESULTS: In the effect of the groups of Chinese angilica root on decreasing viscosity, the effect of whole root group was the best and the effect of main root group was better than that of the tributary root group. Meanwhile the same effect of transplant wild ginseng group was greater than that of dried raw ginseng group. CONCLUSION: This work provided some fundamental evidences for clinical application and pharmacological data for the quality evaluation.

Angelica sinensis↗

Chemico-pharmacological studies on saponins of Panax ginseng C. A. Meyer. I. Chemical part.

For the purpose of clarification of pharmacological actions of ginseng saponins we tried the isolation of ginseng saponins on a larger scale and succeeded in the isolation of eight saponins in a pure state and in sufficient amounts for the pharmacological assay. These eight saponins agreed all completely with the authentic samples of Shibata-Shoji and co-workers in molecular formula of saponins and sapogenins, sugars and TLC. The physical properties of saponins were shown. As other components of ginseng, there were isolated small amounts of panaxadiol, panaxatriol, daucosterol from the first running of column chromatography and mannitol, sucrose and glucose from the ethanol insoluble aqueous extract.

Chromatography, Thin Layer↗

Constituents and pharmacological effects of Eucommia and Siberian ginseng.

The bark and leaves of Eucommia ulmoides Oliv (Eucommiaceae) and "Siberian ginseng" (Ezoukogi in Japanese) prepared from the root bark or stem bark of Eleutherococcus senticosus Maxim (Acanthopanax senticosus Harms) have been used as tonic and anti-stress drug. The extracts of Eucommia showed anti-hypertensive, anti-complementary, anti-oxidative, and anti-gastric ulcer effects, and promoting collagen synthesis, accelating granuloma formation, and other pharmacological effects. The Siberian ginseng exhibited anti-fatigue, anti-stress, immuno-enhancing effect, CNS activity, and anti-depressive effect. By now, 40, 28, and 10 compounds have been isolated from Eucommia ulmoides bark, Eucommia ulmoides leaves, and Siberian ginseng, respectively, and their structures were elucidated. Their pharmacological activities were mainly due to lignans and iridoid glycosides.

Adjuvants, Immunologic↗

[Effect of ginseng injection in treating congestive heart failure and its influence on thyroid hormones].

OBJECTIVE: To observe the effect of Ginseng injection on congestive heart failure (CHF) and its influence on thyroid hormones. METHODS: Fifty-four Patients of CHF were divided into two groups. On the basis of conventional treatment of western medicine, the Ginseng injection was given to the treated group additionally. Blood level of triiodothyronine (T3), thyroxine (T4), reverse triiodothyronine (rT3) and thyroid stimulating hormone (TSH) of all patients were determined before and after treatment by radioimmunoassay. RESULTS: There were significant difference between the treated group and the control group in cure rate and mean course of therapy. The levels of T3 and T4 of all patients were lower than those of the normal control before treatment, and rT3 were higher. Two weeks after treatment, T3 and T4 level in all patients increased significantly and rT3 level significantly decreased(P < 0.05, P < 0.01). CONCLUSION: Ginseng injection has a good effect on patients with CHF. It also has regulatory effect on thyroid hormones.

Adult↗

Korean red ginseng effective for treatment of erectile dysfunction.

Korean red ginseng (Panax ginseng) is a safe, widely available alternative remedy that improves patients' ability to achieve and maintain an erection sufficient for intercourse, even in a population with severe erectile dysfunction. It is a reasonable, nonprescription treatment, especially for men with reservations about taking sildenafil (Viagra). A 500-mg capsule of Korean red ginseng costs about 6 cents, compared with $10 for a tablet of sildenafil.

Comment↗

[Application of gas chromatography-mass spectrometry for determination of the organochlorine pesticide residues in ginseng].

A gas chromatographic-electronionization-mass spectrometric method (GC-EIMS) was developed for the determination of organochlorine pesticide residues in Ginseng plants. The Ginseng samples were extracted with acetone, partioned using petroleum ester with sodium chloride saturated aqueous solution and clean-up with concentrated sulfuric acid. The organochlorine pesticide residues were analysed by GC-MS with monitoring selective mass ions. Ten organochlorine pesticides including alpha, beta, gamma and delta isomers of hexachlorocyclohexane (HCH), pp'-DDE, pp'-DDT, op'-DDT, pp'-DDT, pentachloronitrobenzene (Quintozene, PCNB), and hexachlorobenzene(HCB), were determined simultaneously. Targeted pesticide analytes were separated on DB-5 capillary column. The optimum chromatographic conditions and MS parameters were determined. The average recovery rates for those pesticide residues Ginseng were from 76.6% to 90.1% at 0.1 mg/kg of spiked level, except 58.3% for PCNB. The relative standard deviations were 9.3%-15.0%.

Drug Contamination↗

[Studies on the arbutin biosynthesis by hairy root of Panax ginseng C.A. Mayer].

OBJECTIVE: To study basic conditions for biosynthesis arbutin by the hairy root of Panax ginseng. METHOD: Based on the content of arbutin and the biotransformation rate of hydroquione, these conditions such as the culture stage, the lasting time and the concentration of hydroquione fitting for biosynthesis were found. RESULT: After cultured for 22 days, transferred in fresh B5 medium having 2 mmol.L-1 hydroquione, the hairy root biotransformated hydroquione into arbutin in 24 hours, the bioconversion rate was 89.0% and the content of arbutin in dry root was 13.0%. CONCLUSION: Arbutin, was which never found in the genus of Panax ginseng, can be biosynthesized by the hairy root of Panax ginseng.

Arbutin↗

A novel ginseng saponin metabolite induces apoptosis and down-regulates fibroblast growth factor receptor 3 in myeloma cells.

Ginseng (the root of Panax ginseng C.A. Meyer, Araliaceae) has been used as a crude drug taken orally for preventive and therapeutic purposes in Asian countries as a traditional medicine. In the current study, we have investigated the antitumor effect of a novel ginseng protopanaxadiol saponin bacterial metabolic derivative, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (IH-901), in eight human myeloma cell lines. IH-901 inhibited the proliferation of all myeloma cell lines examined. Despite the fibroblast growth factor receptor 3 (FGFR3) overexpression due to a chromosomal translocation t(4;14)(q16.3;q32.3) in KMS-11 myeloma cells, IH-901 induced apoptosis in a dose- and time-dependent way in this cell line. Treatment of KMS-11 with IH-901 resulted in the formation of internucleosomal DNA fragments, poly (ADP-ribose) polymerase cleavage, and the activation of caspase-3. IH-901 also caused the down-regulation of FGFR3 mRNA and protein expression and inhibited ERK activity in KMS-11 cells. Our results demonstrate that IH-901 induces apoptosis and inhibits FGFR3 expression and signaling in KMS-11 cells, suggesting candidacy for the chemoprevention and the treatment of myeloma.

Apoptosis↗

Behavioral effects of stem-leaves extract from panax ginseng C.A. Meyer.

The behavioral effects of extracts from ginseng stem and leaves (GL), standardized with respect to the total saponines, and from ginseng roots (G115), standardized with respect to the content of ginsenosides were examined in experiments on rats with undisturbed memory and in rats with experimentally-impaired memory (electroconvulsive shock) using the methods for active avoidance (shuttle-box) and passive avoidance (step-down, step-through), the water-maze method and the method for studying exploratory behavior. On multiple administration G115 exerted favorable effects on learning and memory and on the higher nervous activity as a whole. These effects greatly varied with the dose and administration schedules, with the rat strain, with the rat's ability to perform adequately in any particular learning task, and with the behavioral method. The extract from the overground part of ginseng (GL) had, in the majority of cases, an effect weaker than that of G115 or was without effect at all. Based on previous and present results, we discuss the role of the changes in brain biogenic monoamines induced by the extracts for their mechanism of action.

Amnesia↗

Protective effects of vitamin B12, ginseng saponin, and folic acid against murine fetal deformities caused by hyperthermia.

OBJECTIVE: To investigate the protective effects of vitamin B(12), ginseng saponin, and folic acid on mouse embryos subjected to high heat. METHODS: Mice were used for the experiment. RESULTS: After exposure of pregnant mice to high heat, the rates of teratism, stillbirth, and fetal absorption were markedly lower in mice treated with ginseng saponin and folic acid following heat exposure than in untreated mice. There were no significant differences in these rates when comparing mice treated with vitamin B(12) with the untreated mice. CONCLUSIONS: Ginseng saponin and folic acid can lessen injuries to murine embryos caused by high heat, while vitamin B(12) has little protective effect against high temperature except for promoting overall embryonic growth.

Animals↗

[Effects of three different drying methods on extraction and separation of ginsenosides from fresh ginseng].

OBJECTIVE: There exists a close relationship between drying of a fresh herb and its preservation and extraction of efficient components. In order to investigate the influences of different drying methods on extraction and separation of ginsenosides, three drying processes, such as drying in the sun, drying in oven and microwave drying, were used to dry fresh ginsengs. METHODS: The ginsenosides of the dry ginsengs were extracted by poaching and microwave heating, and were separated by foam separation. The concentrations of ginsenosides were measured. RESULTS: Microwave drying saved both time and labor, and was favorable for release of ginsenosides. The ginsenosides could be extracted from the dry ginsengs in a shorter time by microwave heating than poaching. The ginsenosides Rb1, Rb2, Rd could be observably concentrated by foam separation. CONCLUSION: Microwave drying and microwave assisted extraction are efficient and economic methods with a high recovery yield of ginsenosides.

Desiccation↗

Cancer prevention and therapeutics: Panax ginseng.

Panax ginseng has been used as a medicinal plant in China for thousands of years. Current use in Western countries has been diverse, with focused research on cancer therapeutics. P. ginseng apparently mitigates cancer through anti-inflammatory, antioxidant, and apoptotic mechanisms to influence gene expression. Additional mechanisms of investigation include influence on neurotransmission and immunosurveillance. Low toxicity and positive studies in concomitant use with other chemotherapeutic agents is promising. Although there is no conclusive evidence of P. ginseng curing cancer, research has continually found tumor inhibition, especially in the promotion and progression phases.

Apoptosis↗

[Expression of hepatitis B surface antigen gene in ginseng cell].

The recombinant plasmid pBIBSa containing the HBsAg DNA fragment was transferred into Agrobacterium tumefaciens strain LBA4404 directly. Ginseng cells were co-cultivated with Agrobacterium tumefaciens carrying pBIBSa. The ginseng cell lines carrying HBsAg-S gene were obtained. Transgenic cells were checked for the presence of target gene using PCR and RT-PCR. Samples containing the target gene showed a clear band at the site of 700 bp by agarose electrophoresis analysis (Figs. 2, 3). Expression levels determined by ELISA showed maximum expression levels of 184 ng HBsAg/g FW and 0.009% of the total soluble protein. HBsAg in ginseng cells were located both on the membrane and in the nuclei (Fig. 4).

Enzyme-Linked Immunosorbent Assay↗