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High frequency of grossly deleted nef genes in HIV-1 infected long-term slow progressors treated with Korean red ginseng.

To investigate the association between Korean red ginseng (KRG) intake in HIV-1 infected patients and the occurrence of grossly deleted nef genes (gDeltanef), we characterized nef genes in 10 long-term slow progressors (LTSP) infected with HIV-1 subtype B and 34 control patients. LTSP was defined by the annual decrease in CD4 T cells being less than 20/microl over 10 years in the absence of antiretroviral therapy. They were treated with KRG for a prolonged period. Nef genes were amplified from peripheral blood mononuclear cells (PBMC) using nested PCR and the products were sequenced directly. It was observed that the patients CD4 T cell counts decreased from 444 +/- 207/microl to 294 +/- 177/microl over 136 +/- 23 months of KRG intake. This corresponds to an annual decrease in the level of CD4 T cells of 13.3/microl. A total of 479 nef genes were amplified from 137 PBMC samples. Nine out of the 10 patients, 47 (34.3%) out of the 137 samples, and 90 out of the 479 genes revealed gDeltanef. The deletion extended outside the nef gene in 25 gDeltanef obtained from 6 patients. The proportion of samples with gDeltanef (34.3%) was significantly higher than 4.8% in control patients (P < 0.001). In addition, it significantly increased as the duration of KRG intake prolongs (P < 0.01). These data suggest that the occurrence of gDeltanef might be associated with long-term intake of KRG.

Adult↗

Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes.

OBJECTIVE: We previously demonstrated that 3 g American ginseng (AG) reduced postprandial glycemia (PPG) in type 2 diabetic individuals. We investigated whether further reductions can be achieved with escalation of dose and time of AG administration. RESEARCH DESIGN AND METHODS: Ten type 2 diabetic patients (6 men, 4 women; age 63+/-2 years; BMI 27.7+/-1.5 kg/m2; HbA1c 7.3+/-0.3%) were randomly administered 0 g (placebo) or 3, 6, or 9 g ground AG root in capsules at 120, 80, 40, or 0 min before a 25-g oral glucose challenge. Capillary blood glucose was measured before ingestion of AG or placebo and at 0, 15, 30, 45, 60, 90, and 120 min from the start of the glucose challenge. RESULTS: Two-way analysis of variance (ANOVA) demonstrated that treatment (0, 3, 6, and 9 g AG) but not time of administration (120, 80, 40, or 0 min before the challenge) significantly affected PPG (P<0.05), with significant (P = 0.037) interaction for area under the curve (AUC). Pairwise comparisons showed that compared with 0 g (placebo), 3, 6, or 9 g significantly (P<0.05) reduced AUC (19.7, 15.3, and 15.9%, respectively) and incremental glycemia at 30 min (16.3, 18.4, and 18.4%, respectively), 45 min (12.5, 14.3, and 14.3%, respectively), and 120 min (59.1, 40.9, and 45.5%, respectively). However, pairwise comparisons showed no differences between the 3-, 6-, or 9-g doses and any of the times of administration. CONCLUSIONS: AG reduced PPG irrespective of dose and time of administration. No more than 3 g AG was required at any time in relation to the challenge to achieve reductions. Because these reductions included glycemia at the 2-h diagnostic end point, there may be implications for diabetes diagnosis and treatment.

Area Under Curve↗

Protection of C3H/HE J mice from development of Candida albicans infection by oral administration of Juzen-taiho-to and its component, Ginseng radix: possible roles of macrophages in the host defense mechanisms.

Protective effect of a Japanese traditional herbal medicine, Juzen-taiho-to (TJ-48), which was recently reported to augment host-mediated antifungal actions, in Candida albicans-infected mice was further studied. TJ-48, given orally once daily for 5 consecutive days in a dose of 2 g/kg after intravenous infection of C. albicans, prolonged survival period of infected mice of a C3H/He J strain which is characteristic of functional deficiency of macrophages, but did not that of infected mice of a C3H/He N strain with normal macrophage function. Peritoneal macrophages obtained from C3H/He J mice showed a moderate inhibitory activity against Candida growth in vitro. The anti-Candida activity of the macrophages was augmented by the addition of TJ-48 or some component extracts of TJ-48 to the incubation medium. Among such active component extracts is an extract of Ginseng radix which was demonstrated to enhance the anti-Candida activity of macrophages in vitro and to prolong the survival time of C. albicans-infected C3H/He J mice without effect on C3H/He N mice. On the base of these findings, the mechanisms underlying the protective action of TJ-48 against systemic Candida infection was discussed in relation with its possible activity to activate the macrophage function.

Administration, Oral↗

American ginseng transcriptionally activates p21 mRNA in breast cancer cell lines.

American ginseng (AG) has been demonstrated to inhibit breast cancer cell growth in vitro. p21 protein, a universal cell cycle inhibitor, binds cyclin-CDK complexes, an important mechanism in cell cycle regulation. The purpose of this investigation was to determine if AG induces p21 gene expression in hormone sensitive (MCF-7) and insensitive (MDA-MB-231) breast cancer cell lines. Cells grown in steroid stripped medium (SSM) were treated with AG, 17-beta-estradiol (E2), genistein or cycloheximide (CHX). Northern blot analyses were performed using human p21Cip1 and 36B4 cDNA probes. Cell lines were transiently transfected with select mouse p21 CAT reporter constructs, including those lacking a p53 binding site. Cell cycle analyses was performed by FACScan. The results revealed that AG induced p21 mRNA expression in MCF-7 and MDA-MB-231 cells (p=0.0004; p < or =0.0001, respectively). Neither E2 nor genistein alter p21 mRNA expression. CHX, a protein synthesis inhibitor, did not block p21 mRNA expression induced by AG, indicating that p21 is induced as an immediate early gene. AG activated p21 reporter constructs in transfected cells, independent of p53 binding sites. The cell cycle proliferative phase was significantly decreased by AG and increased by E2 (p < or =0.0001). AG may inhibit breast cancer cell growth by transcriptional activation of the p21 gene, independent of p53.

Animals↗

Neuroprotective effect of ginseng total saponins in experimental traumatic brain injury.

In the present study, we investigated whether ginseng total saponins (GTSs) protect hippocampal neurons after experimental traumatic brain injury (TBI) in rats. A moderate-grade TBI was made with the aid of a controlled cortical impact (CCI) device set at a velocity of 3.0 m/sec, a deformation of 3.0 mm, and a compression time of 0.2 sec at the right parietal area for adult male Sprague-Dawley rats. Shamoperated rats that underwent craniectomy without impact served as controls. GTSs (100 and 200 mg/kg) or saline was injected intraperitoneally into the rats immediately post-injury. Twenty-four hours after the injury, the rats underwent neurological evaluation. Contusion volume and the number of hippocampal neurons were calculated with apoptosis evaluated by TUNEL staining. 24 hr post-injury, saline-injected rats showed a significant loss of neuronal cells in the CA2 region of the right hippocampus (53.4%, p<0.05) and CA3 (34.6%, p<0.05) compared with contralateral hippocampal region, a significant increase in contusion volume (34+/-8 microL), and significant increase in neurologic deficits compared with the GTSs groups. Treating rats with GTSs seemed to protect the CCI-induced neuronal loss in the hippocampus, decrease cortical contusion volume, and improve neurological deficits.

Animals↗

[Effect of ginseng fruit saponins on insulin sensitivity index in high fat-fed rats].

OBJECTIVE: To observe the effect of ginseng fruit saponins (GFS) on insulin sensitivity index in high fat-fed rats. METHODS: An animal model of insulin resistance was established by injecting low dose of streptozotocin (STZ) in high fat-fed rats. Effect of GFS on insulin sensitivity was detected with glucose infusion rate (GIR) by euglycemic hyperinsulinemic clamp technique. RESULTS: The level of fasting blood glucose and insulin in untreated group increased more significantly than that in normal control group (P<0.05, P<0.01), while the index of GIR decreased significantly (P<0.01). As compared with the untreated groupìthe parameters of GFS-treated groups were improved significantly in a dosage-dependent manner (P<0.05, P<0.01). CONCLUSION: GFS can improve experimental insulin resistance in rats.

Animals↗

[Effects of ginsenosides extracted from ginseng stem and leaves on glucocorticoid receptor in different viscera in heat-damaged rats].

OBJECTIVE: To evaluate the effects of ginsenosides (GSS) extracted from ginseng stem and leaves on glucocorticoid receptor (GR) in different viscera in heat-damaged rats, and to find out its action mechanism. METHODS: Thirty-two male SD rats were divided into control group and experimental group, and fed 2 mg/d GSS and equal-quantity of distilled water respectively for 7 days. Eight rats of each group were exposed to (42+/-1) degrees C for one hour. The binding activities of GR in brain, thymus, lung and liver cytosols in rats were detected by radioligand binding assay. The expression levels of GR mRNA in brain and liver cytosols were determined by reverse transcription-polymerase chain reaction (RT-PCR) assay. Plasma adrenocorticotropin (ACTH) and corticosterone (CS) concentrations were determined by radioimmunoassay. RESULTS: The binding activities of GR in brain, lung and liver cytosols, and the expression levels of GR mRNA in brain and liver cytosols were all higher in the GSS-treated and heat-damaged rats than those in the untreated heat-damaged rats (P<0.05 or P<0.01). There were no significant differences in plasma concentrations of ACTH and CS between the GSS-treated heat-damaged rats and the untreated heat-damaged rats. CONCLUSION: GSS can lessen the descending degree of the binding activity of GR in brain, thymus, lung and liver cytosols, and such efficacy of GSS may be related to improvement of the expression of GR mRNA.

Animals↗

American ginseng supplementation attenuates creatine kinase level induced by submaximal exercise in human beings.

AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance. METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo) and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk. They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover, the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise, immediately after exercise, and 20, 40, 60, and 120 min after exercise. RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen. CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.

Adult↗

Acute and chronic effects of ginseng total saponin and amphetamine on fixed-interval performance in rats.

The effect of ginseng total saponin (GTS) on amphetamine (AMPH)-induced disruption of fixed-interval (FI) responding in rats was examined. GTS (50 mg/kg) significantly improved the temporal responding impaired by 2 mg/kg of AMPH. A higher dose of 100 mg/kg GTS disrupted performance when given alone; this disruption was reversed by a low dose of AMPH (0.5 mg/kg) and tolerance developed to the effects of GTS with its repeated administration. Neurochemical analysis revealed that GTS (50 mg/kg) attenuated the increase in striatal dopamine caused by AMPH leading to the conclusion that brain dopamine may partially mediate the behavioral effects of GTS.

Amphetamines↗

116 cases of coronary angina pectoris treated with powder composed of radix ginseng, radix notoginseng and succinum.

116 cases of coronary angina pectoris were treated with a powder composed of Radix Ginseng, Radix Notoginseng and Succinum, which was an empirical prescription of Dr. Yue Meizhong ([symbol: see text]), and compared with patients treated Fufang Danshen Tablet (a compound prescription of Radix Salviae Miltiorrhizae) as the control group. Results indicated that the curative effects and ECG in the treated group were better than that in the control group (P < 0.01), so were improvement of general symptoms, physical strength as well as changes of lipid metabolism and microcirculation of nail fold.

Adult↗

American ginseng extract reduces scopolamine-induced amnesia in a spatial learning task.

OBJECTIVE: To determine if HT-1001, an extract of American ginseng, affects scopolamine-induced memory and performance deficits in a spatial learning task, alters brain concentrations of aminergic neurotransmitters, and alters choline uptake in synaptosome preparations. DESIGN: Animal study. ANIMALS: 48 Sprague Dawley rats. INTERVENTIONS: Long-term oral administration of a test material or control solution. Intraperitoneal administration of scopolamine (2 mg/kg) 30 minutes before testing. OUTCOME MEASURES: Performance on Morris water maze task, choline uptake, aminergic neurotransmitter analysis, in vitro monoamine oxidase analysis (of compounds). RESULTS: HT-1001 protected against scopolamine-induced amnesia and increased choline uptake in synaptosomal preparations. HT-1001 did not alter brain concentrations of norepinephrine, dopamine, 5-HT (serotonin), 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleactic acid. HT-1001 had a very weak ability to inhibit monoamine oxidase activity in vitro. CONCLUSIONS: HT-1001 demonstrates a capacity to protect against scopolamine-induced memory deficits.

Animals↗

Glucocorticoid receptor-induced down-regulation of MMP-9 by ginseng components, PD and PT contributes to inhibition of the invasive capacity of HT1080 human fibrosarcoma cells.

We examined the effects of the purified ginseng components, panaxadiol (PD) and panaxatriol (PT), on the expression of matrix metalloproteinase-9 (MMP-9) in highly metastatic HT1080 human fibrosarcoma cell line. A significant down-regulation of MMP-9 by PD and PT was detected by Northern blot analysis. However, the expression of MMP-2 was not changed by treatment with PD and PT. Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. To investigate whether the reduced level of MMP-9 by PD and PT affects the invasive capacity of HT1080 cells, we conducted an in vitro invasion assay with PD and PT treated cells. The results of the in vitro invasion assay revealed that PD and PT reduced tumor cell invasion through a reconstituted basement membrane in the transwell chamber. Because of the similarity of chemical structure between PD, PT and dexamethasone (Dexa), a synthetic glucocorticoid, we investigated whether the down-regulation of MMP-9 by PD and PT were mediated by the nuclear translocation of glucocorticoid receptor (GR). Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry. Western blot and gel retardation assays confirmed the increase of GR in the nucleus after treatment with PD and PT. These results suggest that GR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT1080 cells.

Cell Nucleus↗

[Minor saponins from leaves of Panax ginseng C.A. Meyer].

Five compounds were isolated from the leaves of Panax ginseng and characterized as 20(R)-protopanaxatriol, daucosterine, ginsenoside-F2, ginsenoside-F3 and majoroside-F4 on the basis of spectral analysis and chemical evidence. Among them, majoroside-F4 is obtained from plant for the first time.

Ginsenosides↗

[Active constituents reducing side-effects of prednisone acetate in leaves of Panax ginseng C.A.Mey].

The rise of total lipid, triglyceride and total cholesterol, and the drop of cortisol in serum induced by PA can be significantly inhibited by total ginsenosides in the leaves of Panax ginseng [GSL, 60 mg/(kg.d)]. From GSL ten compounds have been isolated and identified as ginsenoside-Rb2, -Rc, -Rd, -Re, -Rg1 -F3, F2, -Rg2, 20(R)-Rg2 and -Rh1, respectively. Pharmacological study has proved ginsenoside-Re to be the chief active constituent of GSL.

Animals↗

Effect of Panax ginseng and diazepam on brain 5-hydroxytryptamine and its modification by diclofenac in rat.

Wistar male rats pretreated with anti-stress agents like, Panax ginseng (Pg) and diazepam (Diaz) were stressed by restraining for 1 h and 5-HT content of brain and hypothalamus as well as plasma corticosterone were measured spectrophotoflurometrically. Diclofenac (DICLO), a prostaglandin (PG) synthesis inhibitor was used to confirm the role of prostaglandin in restraint stress-induced elevation of central 5-HT correspondingly confirmed by elevation of plasma corticosterone and modification of the above anti-stress agents. Pg, Diaz and DICLO per se did not modify brain and hypothalamic 5-HT in control rats. But they attenuated stress-induced elevation of brain and hypothalamic 5-HT. Anti-stress action of both Pg and Diaz reflected by inhibition of stress-induced elevation of brain and hypothalamic content of 5-HT as also stress-induced concurrent elevation of plasma corticosterone were further diminished by DICLO. The mediatory action of 5-HT in anti-stress effects of Pg and Diaz may be modulated through prostaglandins.

Animals↗

Somatic embryogenesis and ginsenoside production of Panax ginseng in phytohormone-free medium.

Embryogenic cultures of Panax ginseng were established without using phytohormones. Somatic embryos developed from the roots of an in vitro seedling and from excised leaf and petiole segments cultured in half-macro-salt strength Murashige and Skoog medium. Excised leaf and petiole segments were obtained from in vitro germinated seedlings. Plantlets were subsequently obtained from developing somatic embryos in phytohormone-free media. Shoot formation from somatic embryos was influenced by light intensity. The rate of growth and frequency of embryogenesis were improved when cut-up embryogenic tissues were inoculated into liquid media in the dark. The ginsenoside contents of a 4 year-old field-cultivated root, seedlings from zygotic embryos, somatic embryos and embryogenic tissues were determined and compared. Somatic embryos contained 1.7 times the amount of ginsenoside Rb1 and 2.3 times the amount of ginsenoside Re compared to seedlings from zygotic embryos. Ginsenoside Rd, which was absent in the seedlings derived from zygotic embryos, was detected in somatic embryos. Higher ginsenosides Rd and Rg1 levels were found in embryogenic tissues grown on solid media than in tissues grown in liquid media. The total ginsenoside yields, including the ginsenosides Rb1 and Rg1 levels, of cut-up embryogenic tissues, were higher than those of clump tissues.

Culture Media↗

Effects of oral administration of Pfaffia paniculata (Brazilian ginseng) on incidence of spontaneous leukemia in AKR/J mice.

Pfaffia paniculata (Brazilian ginseng) administered subcutaneously and intraperitoneally inhibits growth of allogeneic cancer cells in mice. The goal of this study was to determine whether oral administration of P. paniculata inhibits development of spontaneous leukemia. Four-week-old female AKR/J mice were given oral doses of powdered roots from P. paniculata three times weekly for 8 weeks; controls received phosphate-buffered saline. Enlargement of thymic lymphoma in the mice treated with P. paniculata was significantly suppressed, as compared with controls (128 +/- 67.3 mg versus 219.9 +/- 84.2 mg, respectively; P < .01); proliferation of endogenous recombinant murine leukemia viruses (MuLV) in the thymus was markedly inhibited after the first oral treatment as compared with untreated controls (final age, 28 weeks; P < .05). In normal 3-week-old female AKR/J mice, mortality from thymic lymphoma was delayed markedly after injection into the thymus of cell-free extract of thymus from the experimental female 28-week-old AKR/J mice that received the oral P. paniculata preparation. These results suggest that the agent's suppressive effects on spontaneously occurring leukemia caused by endogenous recombinant MuLV in female AKR/J mice may depend on enhancement of nonspecific immune or cellular immune systems (or both) by the P. paniculata preparation.

Administration, Oral↗

High production of ginsenosides by transformed root cultures of Panax ginseng: effect of basal medium and Agrobacterium rhizogenes strains.

Successful transformation of Panax ginseng was achieved when petiole segments were infected with Agrobacterium rhizogenes ATCC 15834 and MAFF 03-01724. Transformed roots were obtained after galls developed at infected sites. The root morphology, growth and ginsenoside productivity of roots transformed with different bacterial strains differed, and the roots from A. rhizogenes ATCC 15834 grew better and produced much more ginsenosides. Using the ATCC transformed root clone, various liquid culture media were tested to determine the optimum culture medium for ginsenoside production. The root growth was optimum in phytohormone-free Gamborg B5 liquid medium, however highest content of ginsenosides (a total of five ginsenosides 1.88% dry weight) was obtained when the roots were cultured in half-macro-salt strength Gamborg B5 liquid medium. Growth of the roots over a period of 8 weeks showed that their fresh and dry weight continued to increase. The ginsenoside Rb1 content was optimum after 5 weeks of culture. Ginsenoside Rc content began to decrease slightly after the third week of culture. Ginsenosides Rd and Rg1 contents fluctuated, while ginsenoside Re content continued to rise throughout the 8 weeks of culture. Ginsenoside production, however, did not peak within the 8 weeks of culture.

Culture Media↗