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PubMed2002

Diol- and triol-type ginseng saponins potentiate the apoptosis of NIH3T3 cells exposed to methyl methanesulfonate.

In this study we investigated the effect of ginseng saponins on the p53-dependent apoptosis in NIH3T3 cells exposed to methyl methanesulfonate (MMS), an alkylating agent. Trypan blue exclusion assay, cell morphology studies, and apoptotic index determined by acridine orange staining showed that the postincubation of MMS-exposed cells in medium containing diol- (PD) or triol-type (PT) ginseng saponins potentiate the apoptotic cell death. FACS analysis indicated that the increased apoptotic cell population in the saponin-postincubation group was accompanied by the accumulation of cells in G0/G1 phase. By Western blot analyses it was demonstrated that postincubation of saponins increases the expression of p53 and p21 in MMS-exposed cells but decreased that of CDK2, cyclin E and D1, and PCNA. The upregulation of p53 and p21 and downregulation of CDK2 was shown to be p53-dependent in experiments using the p53 antisense oligonucleotide. These results suggest that ginseng saponins contain components potentiating the apoptosis of MMS-exposed NIH3T3 cells via p53 and p21 activation, accompanied with by downregulation of cell cycle-related protein expression.

3T3 Cells↗
PubMedDate not supplied

The nootropic properties of ginseng saponin Rb1 are linked to effects on anxiety.

Previous studies have shown that crude ginseng extracts enhance performance on shock-motivated tasks. Whether such performance enhancements are due to memory-enhancing (nootropic) properties of ginseng, or to other non-specific effects such as an influence on anxiety has not been determined. In the present study, we evaluated both the nootropic and anxiolytic effects of the ginseng saponin Rb1. In the first experiment, 80 five-day-old male chicks received intraperitoneal injections of 0, 0.25, 2.5 or 5.0 mg/kg Rb1. Performance on a visual discrimination task was evaluated 15 minutes, 24 and 72 hours later. Acquisition of a visual discrimination task was unaffected by drug treatment, but the number of errors was significantly reduced in the 0.25 mg/kg group during retention trials completed 24 and 72 hours after injection. Animals receiving higher dosages showed trends towards enhancement initially, but demonstrated impaired performance when tested 72 hours later. Rb1 had no effect on response rates or body weight. In the second experiment, 64 five-day-old male chicks received similar injections of Rb1 (0, 0.25, 2.5 or 5.0 mg/kg) and separation distress was evaluated 15 minutes, 24 and 72 hours later. Rb1 produced a change in separation distress that depended on the dose and environmental condition under which distress was recorded. These data suggest that Rb1 can improve memory for a visual discrimination task and that the nootropic effect may be related to changes in anxiety.

Animals↗
PubMed1999

The effects of Radix Ginseng rubra on cAMP of experimental ischemic myocardium in rats.

The model of SD rats ligated at the proximate left anterior descend (LAD) of coronary was used. The number and dissociation constant of beta receptor were studied by using receptor autoradiography to observe the changes in beta receptor and the effects of Radix Ginseng Rubra on cAMP in experimental ischemic myocardium. The result showed that the number of binding site in simple ligation group (Bmax = 0.279) was obviously higher than that in sham operation group (Bmax = 0.093) and the dissociation constant of simple ligation group (Kd = 12. 431) was higher than that of sham operation group (kd = 1.319). There was a significant difference between the two groups (P < 0.05). It proved that the number of beta receptor was increased and the activity was elevated in myocardial cell membranes after ligation of LAD. The myocardial cAMP level in simple ligation group [(1293.96 +/- 519.36) x 10(-3) nmol/g] was much higher than that in sham operation group [(774.44 +/- 210.55) x 10(-3) nmol/g]; but the level of cAMP in ligation group after receiving Radix Ginseng Rubra treatment (805.02 +/- 362.48 pm/g) was obviously lower than that in simple ligation group (P < 0.01), which was close to the result of sham operation. The results indicated that Radix Ginseng Rubra could decrease the cAMP level in ischemic myocardium.

Animals↗
PubMed1991

[Effects of ginseng on hepatocellular carcinoma in rats induced by diethylnitrosamine--a further study].

The curative effects of Panax ginseng on hepatocellular carcinoma (HCC) in rats induced by diethylnitrosamine (DEN) were further studied. The size of cancerous nodes was quantitatively measured by image analysis instrument. The hepatocellular hyperplastic foci were quantitatively analysed with gamma-GT stain under microspectrophotometer. Pathological changes of hepatocytes were observed under light and electron microscope. The results of the investigation indicated that ginseng had significant inhibitory effect on HCC in rats induced by DEN and prolonged the survival time of the rats with HCC. The mechanism of inhibition of the development of HCC by ginseng was also preliminarily approached.

Animals↗
PubMed2004

Transformation of ginseng saponins to ginsenoside Rh2 by acids and human intestinal bacteria and biological activities of their transformants.

When ginseng water extract was incubated at 60 degrees C in acidic conditions, its protopanaxadiol ginsenosides were transformed to ginsenoside Rg3 and delta20-ginsenoside Rg3. However, protopanaxadiol glycoside ginsenosides Rb1, Rb2 and Rc isolated from ginseng were mostly not transformed to ginsenoside Rg3 by the incubation in neutral condition. The transformation of these ginsenosides to ginsenoside Rg3 and delta20-ginsenoside Rg3 was increased by increasing incubation temperature and time in acidic condition: the optimal incubation time and temperature for this transformation was 5 h and 60 degrees C resepectively. The transformed ginsenoside Rg3 and delta20-ginsenoside Rg3 were metabolized to ginsenoside Rh2 and delta20-ginsenoside Rh2, respectively, by human fecal microflora. Among the bacteria isolated from human fecal microflora, Bacteroides sp., Bifidobacterium sp. and Fusobacterium sp. potently transformed ginsenoside Rg3 to ginsenoside Rh2. Acid-treated ginseng (AG) extract, fermented AG extract, ginsenoside Rh2 and protopanaxadiol showed potent cytotoxicity against tumor cell lines. AG extract, fermented AG extract and protopanaxadiol potently inhibited the growth of Helicobacter pylori.

Animals↗
PubMed1996

No identifiable effect of ginseng (Gericomplex) as an adjuvant in the treatment of geriatric patients.

This study aimed to examine the effect of ginseng as an adjuvant to treatment and rehabilitation of geriatric patients in a double blind, controlled clinical trial. The treatment group (N = 24) received two capsules of Gericomplex (ginseng, vitamins, minerals and trace elements) daily for 8 weeks, while the control group (N = 25) had identical-looking placebo capsules. Participants consisted of 60 geriatric patients, mean age 77.9 years. The principal study variables were length of stay in hospital, and activities of daily living according to the Barthel ADL Index. Cognitive function was assessed at baseline and after 8 weeks, using the Mini-Mental State Examination, the Kendrick Object Learning test, and the Trail Making test. Somatic symptoms, and symptoms of depression and anxiety were scored on a 23-question version of the Hopkins Symptom Checklist. Length of stay in hospital did not differ in the two groups, which also improved to the same degree on the various functional outcome measures, except for the Kendrick Object Learning test, where the placebo group improved more markedly. In conclusion, no identifiable effect of ginseng as an adjuvant to treatment and rehabilitation of geriatric patients was observed.

Adjuvants, Pharmaceutic↗
PubMed2005

Isolation and determination of ginsenosides in American ginseng leaves and root extracts by LC-MS.

Ginseng saponins (ginsenosides) were extracted from the root and leaves of locally cultivated American ginseng (Panax quinquefolium L.). For the isolation of compounds from plant samples three different extraction methods were utilized: accelerated solvent extraction, the ultrasound-assisted solvent extraction and mechanical shaking assisted solvent extraction. The separation of compounds was achieved with a water-acetonitrile gradient system using a C18 reversed-phase column. Target compounds were identified in MS(2) and MS(3) experiments. The relative distribution of these ginsenosides in each root and leaf extract was established. The limit of detection of the method was less than 30 ng/ml. Recovery of ginseng saponins in spiked samples exceeded 80%, while the relative standard deviation ranged from 7.1 to 9.1%. The total concentrations of ginsenosides were 41 and 13 mg/g in root and leaves.

Acetonitriles↗
PubMed2002

Elicitor-like effects of low-energy ultrasound on plant (Panax ginseng) cells: induction of plant defense responses and secondary metabolite production.

In this work we examined the elicitor-like effects of low-energy ultrasound (US) on plant cells with respect to the induction of plant defense responses and secondary metabolite production. Panax ginseng cells in suspension culture were exposed to US (power <or=0.1 W/cm(3) at 38.5 kHz fixed frequency) for short periods of time (30 s-6 min). Two early events in plant defense metabolism and signal transduction pathways, the increased cross-membrane ion fluxes (Ca(2+) influx and K(+) efflux/H(+) influx) and the production of active oxygen species (AOS), were detected in sonicated cultures within 2 min after US exposure. These responses could be induced with small doses of US energy, 0.6-0.8 J/cm(3), and enhanced by increasing US energy within a non-inhibitory range. US treatment stimulated the synthesis of useful secondary metabolites, saponins of ginseng cells, without causing any net loss of the biomass yield of ginseng cell cultures. These results suggest that US can act as a potent abiotic elicitor to induce the defense responses of plant cells and to stimulate secondary metabolite production in plant cell cultures.

Cell Membrane↗
PubMed2002

Production of herbicide-resistant transgenic Panax ginseng through the introduction of the phosphinothricin acetyl transferase gene and successful soil transfer.

Herbicide-resistant transgenic Panax ginseng plants were produced by introducing the phosphinothricin acetyl transferase (PAT) gene that confers resistance to the herbicide Basta (bialaphos) through Agrobacterium tumefaciens co-cultivation. Embryogenic callus gathered from cotyledon explants of P. ginseng were pre-treated with 0.5 M sucrose or 0.05 M MgSO(4 )before Agrobacterium infection. This pre-treatment process markedly enhanced the transient expression of the beta-glucuronidase (GUS) gene. Embryogenic callus was initially cultured on MS medium supplemented with 400 mg/l cefotaxime for 3 weeks and subsequently subcultured five times to a medium containing 25 mg/l kanamycin and 300 mg/l cefotaxime. Somatic embryos formed on the surfaces of kanamycin-resistant callus. Upon development into the cotyledonary stage, these somatic embryos were transferred to a medium containing 50 mg/l kanamycin and 5 mg/l gibberellic acid to induce germination and strong selection. Integration of the transgene into the plants was confirmed by polymerase chain reaction and Southern analyses. Transfer of the transgenic ginseng plantlets to soil was successfully accomplished via acclimatization in autoclaved perlite. Not all of the plantlets survived in soil that had not been autoclaved because of fungal infection, particularly in the region between the roots and leaves. Transgenic plants growing in soil were observed to be strongly resistant to Basta application.

Acclimatization↗
PubMed1991

Prolonged infusion of Panax ginseng saponins into the rat does not alter the chemical and kinetic profile of hormones from the posterior pituitary.

The effect of prolonged administration (i.v.) of commercially available Panax ginseng extract (PGE) on the kinetic profile of the hormones from the posterior pituitary (PP) was studied in male Wistar rats. The rats were infused with 7.36 mg kg-1 h-1 of PGE for 8 days while the hormones from the PP were pulse-labeled at their place of translation in the hypothalamus. The concentration of labeled hormones was analyzed after increasing chase time intervals and compared to controls which were infused with the same volume of isotonic saline. The study revealed: (1) Prolonged administration of PGE prevents the drop in body weight during the 48-h period following stereotaxic surgery. At the end of the ginseng infusion period body weight increased as seen in controls. (2) The concentration of labeled oxytocin, oxytocin-neurophysin, the metabolically converted form of oxytocin-neurophysin and arginine-vasopressin-neurophysin per single PP did not change under prolonged ginseng administration. (3) The amino acid pattern from the ventromedial hypothalamus was not different from controls. From our results we conclude that the physiological effect of PGE in the rat is not based on changes in the translation, conversion rate or the chemical structure of hormones from the PP.

Animals↗
PubMed1996

Ginseng extract scavenges hydroxyl radical and protects unsaturated fatty acids from decomposition caused by iron-mediated lipid peroxidation.

This study was conducted to investigate whether or not the antioxidation effect of ginseng extract directly inhibits decomposition of unsaturated fatty acid caused by iron and hydrogen peroxide-induced lipid peroxidation, and whether this effect involves a hydroxyl radical-scavenging mechanism. Thiobarbituric acid-reactive substances (TBARS), gas chromatography, and electron spin resonance (ESR) spectrometer were used to measure lipid peroxidation, unsaturated fatty acid, and hydroxyl radical. The results showed TBARS formed and the loss of arachidonic acid during lipid peroxidation, and that hydroxyl radical formed by the Fenton reaction were completely inhibited by ginseng extract. This antioxidant effect of ginseng may be responsible for its wide pharmacological actions in clinical practice by a free radical reaction-inhibition mechanism.

Arachidonic Acid↗
PubMed2006

Chemical investigation on Sijunzi decoction and its two major herbs Panax ginseng and Glycyrrhiza uralensis by LC/MS/MS.

Sijunzi decoction consists of Panax ginseng, Poria cocos, Atractylodes macrocephala and Glycyrrhiza uralensis. High performance liquid chromatography coupled with tandem mass spectrometry (LC/MS(n)) was applied to identify and characterize three types of active components, ginsenoside (from P. ginseng), flavonoid and triterpenoid (from G. uralensis) in Sijunzi decoction. Spectra of MS and MS/MS from [M+Na](+) ions of ginsenosides were acquired and interpreted for their identification. Fragmentations with losing masses of 194 or 176Da were the characteristic ions of triterpenoids in the MS/MS analysis. A characteristic fragment ion of the aglycon moiety at m/z 257 from source collision-induced dissociation was observed for flavonoid. LC/MS was also applied for the comparison of relative peak area of major active components between Sijunzi decoction and the single herb extracts. The concentration ratios of major active components detected in the individual herbs of P. ginseng and G. uralensis were found different from those in Sijunzi decoction. The experimental data indicated that the decocting process could result in the difference in the amount of active components.

Chromatography, High Pressure Liquid↗
PubMed2005

Effects of dietary mulberry, Korean red ginseng, and banaba on glucose homeostasis in relation to PPAR-alpha, PPAR-gamma, and LPL mRNA expressions.

Despite lack of scientific evidences to support its therapeutic efficacy, the use of herbal supplements has significantly increased. The purpose of this study was to evaluate the effects of traditional anti-diabetic herbs on the progress of diabetes in db/db mice, a typical non-insulin-dependent model. Five different experimental diets were as follows: control diet, 0.5% mulberry leaf water extract diet, 0.5% Korean red ginseng diet, 0.5% banaba leaf water extract diet, and 0.5% combination diet (mulberry leaf water extract/Korean red ginseng/banaba leaf water extract, 1:1:1). Blood levels of glucose, insulin, HbA1c, and triglyceride were measured every 2 weeks. At 12 weeks of age, animals were sacrificed, and tissue mRNA levels of PPAR-alpha, PPAR-gamma, and LPL were determined. Results indicated that mulberry leaf water extract, Korean red ginseng, banaba leaf water extract, and the combination of above herbs effectively reduced blood glucose, insulin, TG, and percent HbA1c in study animals (p<0.05). We also observed that the increased expressions of liver PPAR-alpha mRNA and adipose tissue PPAR-gamma mRNA in animals fed diets supplemented with test herbs. The expression of liver LPL mRNA was also increased with experimental diets containing herbs. The efficacy was highest in animals fed the combination diet for all of the markers used. These results suggest that mulberry leaf water extract, Korean red ginseng, banaba leaf water extract, and the combination of these herbs fed at the level of 0.5% of the diet significantly increase insulin sensitivity, and improve hyperglycemia possibly through regulating PPAR-mediated lipid metabolism.

Adipose Tissue↗
PubMed2005

A phase I clinical study of Andrographis paniculata fixed combination Kan Jang versus ginseng and valerian on the semen quality of healthy male subjects.

The safety of different doses of Kan Jang--a fixed combination of Andrographis paniculata special extract (SHA-10) and Acanthopanax senticosus--compared to two extensively used medicinal plants, Valeriana officinalis and Panax ginseng in the form of standardized extracts, has been examined. A phase I clinical study was designed to evaluate the effect on semen quality of healthy males in terms of spermatogenesis and quality of semen. The results of the study revealed no significant negative effect of Kan Jang on male semen quality and fertility, but rather a positive trend with respect to the number of spermatozoids in the whole ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and fertility indexes, together with a decrease in the percentage of inactive (diskinetic) forms of spermatozoids. In the group receiving ginseng, no significant negative effects on the fertility parameters were revealed and there was a clear decrease in the percentage of diskinetic forms of spermatozoids. Subjects receiving valerian showed a temporary increase in the percentage of normokinetic spermatozoids and a decrease in diskinetic forms, but these changes had no effect on fertility indices. The results indicate that Kan Jang, ginseng and valerian are safe with respect to effects on human male sterility when administered at dose levels corresponding to approximately 3 times the human daily dose.

Administration, Oral↗
PubMed2006

An electron spin resonance study of gamma-ray irradiated ginseng.

Using electron spin resonance (ESR) spectroscopy, we revealed the presence of four radical species in gamma-ray irradiated ginseng (Agaliaceae). Before irradiation, the representative ESR spectrum of ginseng is composed of a sextet centered at g = 2.0, a sharp singlet at the same g-value, and a singlet at about g = 4.0. The first one is attributable to a hyperfine (hf) signal of Mn2+ ion (hf constant: 7.4 mT). The second one is due to an organic free radical. The third one is originated from Fe3+. Upon gamma-ray irradiation, a new ESR (the fourth) signal was detectable in the vicinity of g = 2.0 region. The progressive saturation behaviors of the ESR signals at various microwave power levels were indicative of different relaxation time for those radicals. The anisotropic ESR spectra were detected by the angular rotation of the sample tube. This is due to the existence of anisotropic microcrystalline in the ginseng powder sample.

Dose-Response Relationship, Radiation↗
PubMed2000

Induction of apoptosis by a novel intestinal metabolite of ginseng saponin via cytochrome c-mediated activation of caspase-3 protease.

Ginseng saponins exert various important pharmacological effects with regard to the control of many diseases including cancer. The novel intestinal bacterial metabolites of ginseng protopanaxadiol saponins have recently been found and isolated after the oral administration of ginseng extract in human and rats. 20-O-(beta-D-Glucopyranosyl)-20(S)-protopanaxadiol (IH-901) formed from ginsenosides Rb1, Rb2, and Rc is of particular interest in cancer chemoprevention and treatment. We investigated the effects of IH-901 on the human myeloid leukemia cell line HL-60 in terms of inhibition of proliferation and induction of apoptosis. IH-901 showed a significant cytotoxic activity in HL-60 cells (IC(50) = 24. 3 microM) following a 96-hr incubation. Treatment of HL-60 cells with IH-901 resulted in the formation of internucleosomal DNA fragments. The dose- and time-dependent induction of apoptosis by IH-901 was demonstrated in sandwich enzyme immunoassay and the results were confirmed by flow cytometric analysis. Morphological examination of IH-901-treated samples showed cells with chromatin condensation, cell shrinkage, and nuclear fragmentation, all typical characteristics of apoptotic cells. The treatment of HL-60 cells with IH-901 caused activation of caspase-3 protease and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. IH-901 did not affect the expression of antiapoptotic protein Bcl-2 but did cause a release of mitochondrial cytochrome c into cytosol. In conclusion, our results demonstrate that IH-901 dramatically suppresses HL-60 cell growth by inducing programed cell death through activation of caspase-3 protease, which occurs via mitochondrial cytochrome c release independently of Bcl-2 modulation. These results may provide a pivotal mechanism for the use of IH-901 in the prevention and treatment of leukemia.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Panaxagin, a new protein from Chinese ginseng possesses anti-fungal, anti-viral, translation-inhibiting and ribonuclease activities.

From the roots of the Chinese ginseng Panax ginseng a protein designated panaxagin with ribonuclease activity, but possessing a sequence distinct from ribonucleases previously reported from ginseng calluses, was isolated. The purification protocol employed comprised extraction with cold saline, (NH4)2SO4 precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration on Superdex 75 by fast protein liquid chromatography. The purified protein was composed of two identical subunits each with a molecular weight of 26 kDa. Its N-terminal amino acid sequence exhibits sites of similarity with the sequences of plant ribosome inactivating proteins and fungal ribonucleases. The spectrum of biological activities of panaxagin encompassed ribonuclease activity toward yeast transfer RNA, translation-inhibitory activity in a rabbit reticulocyte lysate system, and antifungal activity against fungi including Coprinus comatus and Fusarium oxysporum, but not against Rhizoctonia solani. In addition it displayed an inhibitory activity against human immunodeficiency virus reverse transcriptase and succinylation augmented this activity.

Amino Acid Sequence↗
PubMed2001

Ginsenoside production in different phenotypes of Panax ginseng transformed roots.

Transformed roots were obtained after the inoculation of sterile root discs of Panax ginseng C.A. Meyer with Agrobacterium rhizogenes A4. The established hairy root lines displayed three morphological phenotypes when cultured on hormone-free liquid Schenk and Hildebrandt medium. Most of the cultures showed the characteristic traits of hairy roots (HR-M), while others were either callus-like (C-M) or thin (T-M) without branching. The growth rate of the transformed root lines was always higher than that of untransformed roots, showing that the genetic changes caused by the A. rhizogenes transformation conditioned a higher biomass formation. When considering the different transformed root phenotypes, we can observe that the highest ginsenoside production was achieved by HR-M root lines, closely followed by C-M ones, whereas the lowest yield was reached by T-M root phenotype. The study of the integration of the TL-DNA and TR-DNA fragments of the pRiA4 in the root genome showed that the aux1 gene was always detected in HR-M and C-M root phenotypes which presented the highest biomass and ginsenoside productions. This fact suggests a significant role of aux genes in the morphology of Panax ginseng transformed roots. The ginsenoside pattern of transformed roots varied according to their morphology, although the ginsenoside contents of the Rg group was always higher than that of the Rb group. From our results, we can infer the potential of some root phenotypes of Panax ginseng hairy root cultures for an improved ginsenoside production.

Ginsenosides↗