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PubMed2005

Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor alpha.

We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated pathways, using a PPARalpha-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPARalpha ligand Wy14,643. In contrast, no effect was detected in the PPARalpha-null mice. Testing of eight main ginsenosides on PPARalpha reporter gene expression indicated that Rf was responsible for the effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPARalpha-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPARalpha.

Animals↗
PubMed2003

In vitro inhibition of adrenal catecholamine secretion by steroidal metabolites of ginseng saponins.

We reported previously that the protopanaxatriol saponins in Panax ginseng greatly reduce the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh). However, protopanaxadiol saponins showed only slight inhibitory effects. Recent studies have demonstrated that oligosaccharides connected to the hydroxyl groups of the aglycone in ginseng saponins (ginsenosides) are in turn hydrolyzed in the digestive tract and absorbed into the circulation following oral administration of ginseng. Therefore, the present study was performed to investigate the effects of the major ginsenoside metabolites (M1, M2, M3, M4, M5, M11, and M12) on catecholamine secretion. All of these metabolites were shown to be potent inhibitors of ACh-evoked secretion, and M4 was the most effective. M4 blocked not only the ACh-induced Na(+) influx into the chromaffin cells but also the ACh-induced inward current into Xenopus oocytes expressing human alpha 3 beta 4 neuronal nicotinic ACh receptors. M4 reduced the secretion induced by high K(+), an activator of voltage-sensitive Ca(2+) channels, to a much lesser extent than that evoked by ACh. M1, M2, M3, M5, and M12 are protopanaxadiol saponin-derived metabolites. Therefore, these results imply that the protopanaxadiol saponins are prodrugs, and they show more potent inhibitory activity following metabolism in the digestive tract. The results further suggest that the metabolites act on nicotinic ACh receptors, blocking Na(+) influx through the receptors, and consequently reduce the catecholamine secretion from bovine adrenal chromaffin cells. The inhibitory effect of ginsenoside metabolites is probably one of the mechanisms of action responsible for the pharmacological effects of ginseng.

Animals↗
PubMed2003

Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease.

The herbal remedy, ginseng, has recently been demonstrated to possess neurotrophic and neuroprotective properties, which may be useful in preventing various forms of neuronal cell loss including the nigrostriatal degeneration seen in Parkinson's disease (PD). In these studies, we examine the potential neuroprotective actions of the ginseng extract, G115, in two rodent models of PD. Animals received oral administration of G115 prior to and/or following exposure to the parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in mice, or its toxic metabolite, 1-methyl-4-phenylpyridinium (MPP(+)), in rats. Such treatment significantly and dramatically blocked tyrosine hydroxylase-positive cell loss in the substantia nigra and reduced the appearance of locomotor dysfunction. Thus, oral administration of ginseng appears to provide protection against neurotoxicity in rodent models of PD. Further examination of the neuroprotective actions of ginseng and its various elements may provide a potential means of slowing the progress of PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Effect of Panax ginseng extract (G115) on angiotensin-converting enzyme (ACE) activity and nitric oxide (NO) production.

This study investigates the effects of the Panax ginseng (Araliaceae) extract G115 on angiotensin-converting enzyme (ACE) activity and nitric oxide (NO) in cultured human endothelial cells from umbilical veins (HUVEC) and bovine mesenteric arteries (BMA). In HUVEC, ACE activity was significantly reduced after 10 min incubation with aqueous extract of ginseng 5.0 and 10 mg/ml. This effect was additative with the inhibition of the traditional ACE inhibitor enalaprilat. No effect was seen on NO production from the cells. Angiotensin I-induced contraction of BMA was significantly attenuated by 0.1 and 0.5 mg/ml ginseng, while no endothelium-dependent or -independent relaxation was seen. In conclusion, extract of Panax ginseng (G115) inhibits ACE activity, but does not affect NO production in HUVEC and BMA.

Angiotensin I↗
PubMed2004

Protective effect of ginseng extract against apoptotic cell death induced by 2,2',5,5'-tetrachlorobiphenyl in neuronal SK-N-MC cells.

Oxidative stress plays an important role in the pathological processes of neurodegenerative diseases. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) induces apoptotic death in human neuronal SK-N-MC cells, as demonstrated by gel electrophoresis, which demonstrates the proteolytic cleavage of beta-catenin and poly(ADP-ribose) polymerase (PARP) and the characteristic ladder patterns of DNA fragmentation. In the present study, we investigated whether Panax ginseng extract protect human neuronal SK-N-MC cells from PCB 52-induced apoptosis. The addition of 500 microg/ml of ginseng extract to a culture medium significantly protected neuronal cell from the apoptosis mediated by PCB 52 and remarkably attenuated lipid peroxidation, the generation of reactive oxygen species, and DNA fragmentation, and markedly reduced the PCB 52 induced proteolytic cleavage of beta-catenin and PARP. These results show that Panax ginseng extract protects human neuronal SK-N-MC cells from the apoptosis induced by PCB 52. We suggest that Panax ginseng extracts may protect neuronal cells from oxidative injury.

Apoptosis↗
PubMed2003

The inhibitory effect of ginseng saponins on the stress-induced plasma interleukin-6 level in mice.

The effect of ginseng saponins on plasma interleukin-6 (IL-6) in non-stressed and immobilization-stressed mice were investigated. Ginseng total saponins, ginsenosides Rb2, Rg1 and Rd administered intraperitoneally attenuated the immobilization stress-induced increase in plasma IL-6 level. But, intracerebroventricular injection of each ginsenoside did not affect plasma IL-6 level induced by immobilization stress. Ginsenosides Rb2, Rd and Rg1 significantly decreased norepinephrine and/or epinephrine-induced increase of IL-6 level in macrophage cell line (RAW 264.7). Thus, it can be suggested that the inhibitory action of ginseng saponins against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking norepinephrine- and/or epinephrine-induced increase of IL-6 level in macrophage rather than in the brain. Ginseng saponins might be proposed as a possible candidate in the research or therapeutic modulation of stress-related disorders.

Animals↗
PubMed2005

Herbal remedies in the management of diabetes: lessons learned from the study of ginseng.

The only example of an approved antidiabetic drug that was developed from a herbal source with a long history of use for diabetes is the biguanide Metformin from French lilac (Galega officinalis). Clinical data are beginning to emerge that support antidiabetic indications for several other herbs. This viewpoint discusses the state of the evidence for their clinical antidiabetic efficacy. One of the most studied herbs, ginseng (Panax spp.), is used as a model to illustrate the challenges associated with achieving reproducible clinical efficacy. It is concluded that the best evidence for clinical efficacy in diabetes remains for ginseng. But overall insufficient evidence exists to claim a diabetes indication for herbs. The experience with ginseng suggests that although reproducible efficacy may be achieved using an acute postprandial clinical screening model to select an efficacious ginseng batch, dose, and time of administration, there is a need to develop a basis for standardization that ties the composition of herbs to efficacy. In absence of such standardization, the use of herbs in diabetes must be approached cautiously.

Complementary Therapies↗
PubMed2004

Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats.

Previously we reported that oral application of red ginseng significantly ameliorated learning deficits in aged rats and young rats with hippocampal lesions. In the present study, we investigated the effects of the nonsaponin fraction of red ginseng on learning deficits in aged rats in behavioral studies and those on long-term potentiation (LTP) in the hippocampal CA3 subfield in young rats in electrophysiological studies. In the behavioral studies, three groups of rats [aged rats with and without oral administration of the nonsaponin fraction of red ginseng and young rats] were tested with the three types of spatial-learning task [distance movement task (DMT), random-reward place search task (RRPST), and place-learning task (PLT)] in a circular open field. The results in the DMT and RRPST indicated that motivational and motor activity was not significantly different among the three groups of rats. However, performance of the aged rats without nonsaponin was significantly impaired in the PLT when compared with the young rats. Treatment with nonsaponin significantly ameliorated deficits in place-navigation learning in the aged rats in the PLT. In the electrophysiological studies, effects of nonsaponin on the LTP in the CA3 subfield of the hippocampal slices were investigated in vitro. Pretreatment with nonsaponin significantly augmented the increase in population spike amplitudes in the CA3 subfield after LTP induction. These results suggest that the nonsaponin fraction of red ginseng contains important substances to improve learning and memory in aged rats and that this amelioration by nonsaponin might be attributed partly to augmentation of LTP in the CA3 subfield.

Aging↗
PubMed2004

Selection of high ginsenoside producing ginseng hairy root lines using targeted metabolic analysis.

To develop an experimental system for studying ginsenoside biosynthesis, we generated thousands of ginseng (Panax ginseng C.A. Meyer) hairy roots, genetically transformed roots induced by Agrobacterium rhizogenes, and analyzed the ginsenosides in the samples. 27 putative ginsenosides were detected in ginseng hairy roots. Quantitative and qualitative variations in the seven major ginsenosides were profiled in 993 ginseng hairy root lines using LC/MS and HPLC-UV. Cluster analysis of metabolic profiling data enabled us to select hairy root lines, which varied significantly in ginsenoside production. We selected hairy root lines producing total ginsenoside contents 4-5 times higher than that of a common hairy root population, as well as lines that varied in the ratio of the protopanaxadiol to protopanaxatriol type ginsenoside. Some of the hairy root lines produce only a single ginsenoside in relatively high amounts. These metabolites represent the end product of gene expression, thus metabolic profiling can give a broad view of the biochemical status or biochemical phenotype of a hairy root line that can be directly linked to gene function.

Ginsenosides↗
PubMed2002

Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults.

It has previously been demonstrated in separate studies that single doses of Ginkgo biloba, Panax ginseng, and a combination of the two extracts can improve different aspects of cognitive performance in healthy young volunteers. The present study directly compared the effects of single doses of G. biloba, ginseng, and a product combining the two on aspects of mood and cognitive performance in the same cohort of healthy, young adult volunteers. The study followed a randomised placebo-controlled, double-blind, balanced, cross-over design. Twenty participants received 360 mg of ginkgo, 400 mg of ginseng, 960 mg of a product combining the two extracts, and a matching placebo. Treatment order was dictated by random allocation to a Latin square, with a 7-day wash-out period between treatments. Cognitive testing comprised completion of the Cognitive Drug Research (CDR) computerised assessment battery and two serial subtraction mental arithmetic tasks. Mood was assessed with Bond-Lader visual analogue scales. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4, and 6 h after the day's treatment was taken. The results largely supported previous findings. All three treatments were associated with improved secondary memory performance on the CDR battery, with the ginseng condition evincing some improvement in the speed of performing memory tasks and in the accuracy of attentional tasks. Following ginkgo and the ginkgo/ginseng combination performance of both the Serial Threes and Serial Sevens, subtraction tasks was also improved at the later testing sessions. No modulation of the speed of performing attention tasks was evident. Improvements in self-rated mood was also found following ginkgo and to a lesser extent the combination product.

Adolescent↗
PubMed2001

Ultrasound-induced physiological effects and secondary metabolite (saponin) production in Panax ginseng cell cultures.

This work was aimed at the effects of ultrasound (US) on the growth and secondary metabolite biosynthesis of cultured plant cells. Suspension cultures of Panax ginseng cells were exposed to US at power density below 82 mW/cm3 for short periods of time (1-4 min) in a US bath (38.5-kHz fixed frequency and 810 W maximum peak power). Under most exposure conditions, US stimulated the biosynthesis of secondary metabolites, the ginsenoside saponins of ginseng cells, increasing the total saponin content of the cell by up to 75%. The growth and viability of ginseng cells were usually depressed immediately after the exposure to US, but recovered gradually to levels similar to those of a normal culture in a few days, with virtually no net loss of biomass yield at the end of the culture period. At some lower US doses, sonicated cultures could even reach slightly higher biomass yields than that of normal cultures. The effects of US on cell growth and secondary metabolite yield showed a significant correlation with the total US energy emitted (i.e., the product of US power and exposure time). Mechanical stress and microstreaming induced by acoustic cavitation were considered as the most possible causes of the various physiological effects of US on ginseng cells. In particular, the stimulation of secondary metabolite production by US may be a result of US-induced plant cell defense response.

Cells, Cultured↗
PubMed2000

The aphrodisiac and adaptogenic properties of ginseng.

Ginseng is the root of the perennial herbs of Panax quinquefolium and Panax ginseng which contain a series of tetracyclic triterpenoid saponins (ginsenosides) as active ingredients. It is considered a tonic or adaptogenic that enhances physical performance (including sexual), promotes vitality and increases resistance to stress and ageing. The adaptogenic properties of ginseng are believed to be due to its effects on hypothalamic-pituitary-adrenal axis, resulting in elevated plasma corticotropin and corticosteroids levels. When used appropriately, ginseng appears to be safe. Nevertheless, documented side effects include hypertension, diarrhoea, restlessness, mastalgia and vaginal bleeding.

Aphrodisiacs↗
PubMed2003

Ginseng increases intestinal elimination of albendazole sulfoxide in the rat.

Herbal products show potential drug interactions, some of them with adverse effects. The main aim of this work was to study the effect of Panax ginseng on the intestinal elimination of the benzimidazole derivative albendazole sulfoxide (ABZSO). An upper small intestine segment was isolated and perfused in situ with saline, while ABZSO solution (10 mg/kg i.v.) was administered intravenously. Blood samples and intestinal secretion were collected over 60 min and analysed by HPLC. The intestinal clearance of ABZSO was 0.106+/-0.010 ml/min. Systemic co-administration of ginseng (10 mg/kg i.v.) increased significantly (P<0.05) the clearance of ABZSO (0.132+/-0.005 ml/min). The increase in ABZSO elimination could be the result of the effect of ginseng on metabolic pathways. These results highlight the interactions between herbal products (sometimes dietary constituents) and drugs such as benzimidazoles, since ginseng modifies the luminal clearance of this anthelminthic drug and could potentially interfere with drugs that undergo the same intestinal processes.

Albendazole↗
PubMed2004

Randomized controlled trial of Siberian ginseng for chronic fatigue.

BACKGROUND: Chronic fatigue greatly affects quality of life and is a common reason for consulting a physician. Since conventional therapy is often of limited help, fatigued patients may use herbal treatments. This randomized controlled trial evaluated the effectiveness of Siberian ginseng. METHOD: Subjects were recruited from advertisements in Iowa (82%) and members of chronic fatigue syndrome support groups (18%). Potential subjects were required to have substantial fatigue > or = 6 months with no identifiable cause. The mean change in a fatigue measure was compared for placebo and Siberian ginseng at 1 and 2 months. Comparisons were for all subjects and for subjects with characteristics previously identified in the literature as important for categorizing chronic fatigue. RESULTS: Ninety-six subjects were randomized to treatment groups, and 76 provided information at 2 months of follow-up. Fatigue among subjects assigned to either placebo or Siberian ginseng was substantially reduced during the study, but differences between treatment groups were not statistically significant in the full sample. Fatigue severity and duration had a statistically significant interaction with response to Siberian ginseng at the P < 0.05 level. Treatment was effective at 2 months for 45 subjects with less severe fatigue (P = 0.04 unadjusted for multiple comparisons) and for 41 subjects with fatigue for > or = 5 years (P = 0.09 unadjusted for multiple comparisons). CONCLUSION: Overall efficacy was not demonstrated. However, the findings of possible efficacy for patients with moderate fatigue suggests that further research may be of value.

Adult↗
PubMedDate not supplied

Improvement of Panax notoginseng cell culture for production of ginseng saponin and polysaccharide by high density cultivation in pneumatically agitated bioreactors.

A Panax notoginseng cell culture was successfully scaled up from shake flask to 1.0-L bubble column reactor and concentric-tube airlift reactor. High-density bioreactor batch cultivation was carried out using a modified MS medium. The maximum cell density in batch cultures reached 20.1, 21.0 and 24.1 g/L in the shake flask, bubble column and airlift reactors, respectively, and their corresponding biomass productivity was 950, 1140 and 1350 mg/(L x d) for each. The productivity of ginseng saponin was 70, 96 and 99 mg/(L x d) in the flask, bubble column and airlift reactors, respectively; and the polysaccharide productivity reached 104, 119 and 151 mg/(L x d) for each. Furthermore, a fed-batch cultivation strategy was developed on the basis of specific oxygen uptake rate (SOUR), i.e., sucrose feeding before a sharp decrease of SOUR, and the highest cell density of 29.7 g/L was successfully achieved in the airlift bioreactor on day 17 with a very high biomass productivity of 1520 mg/(L x d). The concentrations of ginseng saponin and polysaccharide reached about 2.1 and 3.0 g/L, respectively, and their productivity was 106 (saponin) and 158 mg/(L x d) (polysaccharide). This work successfully demonstrated the high-density bioreactor cultivation of P. notoginseng cells in pneumatically agitated bioreactors and the reproduction of the shake flask culture results in bioreactors. The cell density, biomass productivity, production titer and productivity of both ginseng saponin and polysaccharide obtained here were the highest that have been reported on a reactor scale for all the ginseng species.

Biomass↗
PubMedDate not supplied

Scale-up of centrifugal impeller bioreactor for hyperproduction of ginseng saponin and polysaccharide by high-density cultivation of panax notoginseng cells.

Scale-up of a novel centrifugal impeller bioreactor (CIB) was demonstrated for production of valuable plant-specific secondary metabolites by high-density cell cultures. Initial kLa was identified to be a key factor affecting cell growth and production of ginseng saponin and polysaccharide by high-density cultivation of Panax notoginseng cells in a 3-L CIB. A high level of ginseng saponin and polysaccharide production was obtained at an initial kLa value of 30.2 h(-1). A maximum dry cell weight (DW) and production titer of ginseng saponin and polysaccharide reached 22.0 +/- 0.3, 1.5 +/- 0.1, and 2.7 +/- 0.2 g/L on day 15 with their corresponding productivity of 1140 +/- 42, 81 +/- 8, and 150 +/- 17 mg/(L.d), respectively. Based on initial kLa level, the CIB high-cell-density cultivation process was successfully scaled up from 3 L to 30 L. A maximum DW and production titer of ginseng saponin and polysaccharide in a 30-L CIB reached 25.5 +/- 0.5, 1.7 +/- 0.1, and 2.9 +/- 0.1 g/L (on day 15) at an initial kLa value of 28.7 h(-1), respectively, and their corresponding productivity was 1340 +/- 56, 91 +/- 9, and 164 +/- 15 mg/(L.d). Furthermore, by adopting a fed-batch cultivation strategy, a maximum DW and concentrations of total saponin and polysaccharide in the 30-L CIB were enhanced to 30.3 +/- 1.0, 2.1 +/- 0.1, and 3.5 +/- 0.2 g/L with their corresponding productivity of 1467 +/- 87, 102 +/- 13, and 179 +/- 18 mg/(L.d), respectively. The work suggests that the CIB may have great potential in large-scale high-density plant cell cultures for efficient production of useful secondary metabolites.

Bioreactors↗
PubMed2002

Authentication of Panax ginseng and Panax quinquefolius using amplified fragment length polymorphism (AFLP) and directed amplification of minisatellite region DNA (DAMD).

AFLP profiles characteristic to Panax ginseng and Panax quinquefolius were generated using primers E-AGG/M-CAA. P. ginseng samples from different farms in China and Korea are homogeneous genetically [similarity index (SI) = 0.88-0.99], whereas samples of P. quinquefolius from different sources are much more heterogeneous (SI = 0.64-0.96). Detailed analysis of one of the polymorphic bands in P. ginseng led to the identification of a minisatellite Pg2, which contains eight repeats of 5'-AGGACTCATCACATTGTTACTC. The minisatellite DNA was consequently used in directed amplification minisatellite region DNA analysis to authenticate the two ginsengs.

Base Sequence↗
PubMed2004

Determination of ginsenosides Rb1, Rc, and Re in different dosage forms of ginseng by negative ion electrospray liquid chromatography-mass spectrometry.

A method based on high-performance liquid chromatography (HPLC) and negative ion electrospray mass spectrometry (LC-MS) has been used to determine ginsenosides Rb1, Rc, and Re in six different samples of ginseng. These included a liquid extract, capsules, tea bags, and an instant tea. It was found that four of the six samples had detectable levels of at least one of the ginsenosides. The liquid extract, capsules, instant tea, and tea bags labeled ginseng had ginsenosides. The labels on the two samples that did not have ginsenosides indicated that they were a mixture of green tea, licorice, and ginseng. Also, 13C NMR was used to identify the types of complex carbohydrates present in the samples. One of the samples of tea bags had none of the ginsenosides, but did have complex carbohydrates found in most of the other samples. The instant tea had all three ginsenosides, but had no complex carbohydrates, only sucrose. The amounts of ginsenosides found in standard doses from six different sources of ginseng varied considerably. It was found that steeping a tea bag for a longer time than that recommended on the label produced a larger recovery of ginsenosides and that reusing a tea bag produced even higher recoveries.

Chromatography, High Pressure Liquid↗