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The effect of fraction 4 of the extract from the roots of Panax ginseng, Oura, on DNA and protein syntheses was investigated. Addition of fraction 4 in vitro stimulated DNA and protein syntheses in testes. The stimulating effect was reduced by pretreatment with cycloheximide. This might give some evidence about the stimulatory effect of ginseng on spermatogenesis.
Irritation for 10 min of the posterior spinal root in the frog Rana temporaria (electrical stimulation 50 imp/sec, threshold power 4) results in decreasing size of the motoneurons and their nuclei and in appearing pycnomorphous type of neurons. Simultaneously, peculiar changes in cellular ultrastructure connected with inhibition of protein synthesis are observed. When the ginseng preparation is administered to intact animals, an increased excitability of the spinal centers, as well as increasing volume of the motoneuronal nuclei and certain ultrastructural shifts demonstrating activation of protein synthesis and cellular energy are observed. When the ginseng preparation is preliminary administered to the frogs, before a high-frequency synaptic activation of the motoneurons, it protects the cells from pathological changes and pycnotic shrinkage.
Ether, ethanol and aqueous extracts of ginseng were serially prepared from Korean ginseng plants. Each extract in the dose of 40 mg/kg was administered intravenously to ten dogs under light halothane anesthesia while 11 cardiovascular variables were compared during the ensuing two hours. The variable included cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2 and base deficit. Following the administration of the ether extract (40 mg/kg) the heart rate and the central venous pressure decreased significantly. The administration of ethanol extract (40 mg/kg) caused a significant decrease in the heart rate and the mean arterial pressure. After the administration of the aqueous extract (40 mg/kg) the cardiac output, stroke volume and central venous pressure were significantly decreased, while the total peripheral resistance was significantly increased.
The influence of official drug bioginseng produced from cultivated cells of ginseng radix (Panax ginseng C. A. Mey) on carcinogenesis of the mammary gland was studied. Adenocarcinomas of the mammary gland were induced in rats by single intramammary injections of N-methyl-N-nitrosourea (MNU) at a dose of 1 mg per gland into the tissues of all 12 mammary glands. Bioginseng was given per os at a daily dose of 0.5 ml per rat for 27 weeks beginning 1 week after the MNU administration. Bioginseng and the control MNU-group decreased the incidence and multiplicity of the mammary gland tumors at 44 and 62% respectively. By radioimmune assay it was found that bioginseng normalised abnormally high level of estradiol in blood of rats treated by MNU.
The 252-Cf plasma desorption mass spectrometry (252-Cf PDMS) determination or confirmation of the ginsenoside saponins has been proposed to investigate the composition of high performance liquid chromatography (HPLC) peaks of ginseng tinctures and galenic preparations. That ionization technique is well suitable for the analysis of natural mixtures of these saponins. The 252-Cf PD mass spectra of standard ginsenosides Rb1, Rb2, Rc, Re, Rg1, Rd, NG-R2, Z-R1 contain the peaks of two types of ions, namely, molecular adduct ions (MAI) and aglycone ions. By mass the latter may be referred to either protopanaxadiol or protopanaxatriol. The masses of MAI and aglycone ions are determined by the carbohydrate chains. The collected HPLC fractions of P ginseng tincture can be tested for content of ginsenosides. After studying two MAI peaks from the 252-Cf PD mass spectra of the basic ginsenosides, an example of distinction between two galenic preparations from different Panax has been shown.
The aim of the study was to determine the properties of a standardized extract of ginseng root in inducing a higher immune response in vaccination against influenza. Attention was also paid to the common cold in this multicentre, two-arm, randomized, placebo-controlled, double-blind investigation. A total of 227 volunteers who visited 3 private practices in Milan received daily oral capsule doses of either placebo (113) or 100 mg of standardized ginseng extract Ginsana G 115 (114) for a period of 12 weeks within which they received an anti-influenza polyvalent vaccination at week 4. As a result, while the frequency of influenza or common cold between weeks 4 and 12 was 42 cases in the placebo group, it was only 15 cases in the G115 group, the difference being statistically highly significant (p < 0.001). Whereas antibody titres by week 8 rose to an average of 171 units in the placebo group, they rose to an average of 272 units in the G115 group (p < 0.0001). Natural killer (NK) activity levels at weeks 8 and 12 were nearly twice as high in the G115 group as compared to the placebo group (p < 0.0001). In all the volunteers, laboratory values of 24 safety parameters showed no significant differences between the end and the beginning of the 12-week study in either of the groups. There were only 9 adverse events in the study, the principal one being insomnia.
Sixty-six patients have been treated with Panax Ginseng C.A. Meyer extract, of whom 30 oligoastenospermic sine causa (group A), 16 oligoastenospermic with idiopathic varicocele (group B). Twenty age-matched volunteers were used as controls (group C). Use of Panax Ginseng extract showed an increase in spermatozoa number/ml and progressive oscillating motility, an increase in plasma total and free testosterone, DHT, FSH and LH levels, but a decrease in mean PRL. It is suggested that ginsenosides may have an effect at different levels of the hypothalamus-pituitary-testis axis.
By bioassay-guided fractionation using mushroom tyrosinase, p-coumaric acid was characterized as the principal tyrosinase inhibitor from the fresh leaves of Panax ginseng (Araliaceae). It inhibited the oxidation of L-tyrosine more strongly than that of L-3, 4-dihydroxyphenylalanine (L-DOPA) by this enzyme. On the basis of this finding, various related phenylpropanoid analogues were also tested in order to gain new insights into their structural criteria.
Superoxide dismutase (SOD) converts superoxide radical to H(2)O(2), which is in turn broken down to water and oxygen by catalase. Thus, SOD and catalase constitute the first coordinated unit of defence against reactive oxygen species. A wide variety of chemical and environmental factors are known to induce these antioxidant enzymes. Here, we examined the effect of ginseng saponins on the induction of SOD and catalase gene expression. To explore this possibility, the upstream regulatory promoter region of Cu/Zn superoxide dismutase (SOD1) and catalase genes were linked to the chloramphenicol acetyltransferase (CAT) structural gene and introduced into human hepatoma HepG2 cells. Total saponin and panaxatriol did not activate the transcription of SOD1 and catalase genes but panaxadiol increased the transcription of these genes about 2-3 fold. Among the panaxadiol ginsenosides, the Rb(2) subfraction appeared to be a major inducer of SOD1 and catalase genes. The specificity of the Rb(2) effect was further confirmed by time course- and dose-dependent induction experiments. These results suggest that the panaxadiol fraction and its ginsenosides could induce the antioxidant enzymes which are important for maintaining cell viability by lowering the level of oxygen radical generated from intracellular metabolism.
The levels of corticosterone were estimated by the HPLC method in the adrenal glands of stressed (5 h constant swimming) male albino mice treated with Trichopus zeylanicus, Withania somnifera and Panax ginseng preparations and compared with non-treated stressed and normal controls. The treatments increased the corticosterone levels in all the groups. The physical endurance (increased survival time) of swimming mice also increased in all the treated groups, except in the group treated with Withania somnifera powder (500 mg/kg, p.o.).
Two new polyines showing good cytotoxic activity against L1210 cells were isolated from Korean ginseng root. These were 3-acetyloxy-9,10-epoxy-heptadec-1-en-4,6-diyne(acet ylpanaxydol, ED50 = 0.52 microgram/ml) and 10-chloro-3,9-dihydroxyheptadec-1-en-4,6-diyne(Panaxydolc hlorohydrin, ED50 = 0.50 microgram/ml).
Aberrant expression of matrix metalloproteinase-9 (MMP-9) is implicated in the process of invasion and angiogenesis of malignant tumors as well as in inflammatory diseases of the CNS. Therefore, the development of compounds that can inhibit or suppress MMP-9 is required to treat brain tumors. We investigated the effects of a ginseng saponin metabolite, compound K (20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol), on MMP-9 expression in human astroglioma cells. Compound K significantly inhibited the secretion and protein expression of MMP-9 induced by PMA. The inhibitory effect of compound K on MMP-9 expression correlated with decreased MMP-9 mRNA levels and suppression of MMP-9 promoter activity. The compound K-mediated inhibition of MMP-9 gene expression appears to occur via AP-1 because its DNA-binding and transcriptional activities were suppressed by the agent. Furthermore, compound K significantly repressed the PMA-mediated activation of p38 MAPK, ERK and JNK, which are upstream modulators of AP-1. Finally, compound K inhibited the in vitro invasiveness of glioma cells. Therefore, inhibition of MMP-9 expression by compound K might have therapeutic potential for controlling the growth and invasiveness of brain tumors.
The variation in panaxoside content of roots and commercial products of Panax ginseng and P. quinquefolium was evaluated by a new spectrodensitometric TLC method. The method is rapid and applicable to all commercial products, and it has a relative standard deviation of 6.4%. Panaxoside patterns of slurry-filled capsules and root extracts most closely resembled those of whole roots. Tablets did not contain detectable panaxosides while teas and granules for infusion yielded only low concentrations. The wide variation among these products indicates the need for more rigid control.
A new HPLC-APCI/MS method for the identification of ginsenosides has been developed. The analyses were performed on a reversed-phase C18 column using a binary eluent (acetonitrile and water) under gradient conditions. Although APCI is a high-temperature evaporative process, HPLC-APCI/MS could effectively identify thermo-labile ginsenosides. The [M-H]- ions and the thermal degradation ions of ginsenosides could be clearly observed under negative and positive ion conditions, respectively, and these were used to identify the molecular masses, the aglycone structures and the sugar groups of ginsenosides. APCI/MS can provide more explicit information than ESI/MS for identifying and distinguishing ginsenosides. Using the HPLC-APCI/MS method, 35 ginsenosides were identified in Panax ginseng.
Siberian ginseng, the root and stem bark of Acanthopanax senticosus Harms, has been used as a tonic and adaptogen to strengthen qi in traditional Korean medicine. The neuroprotective effects of water extracts of A. senticosus (ASW) were investigated in transient middle cerebral artery occlusion (MCAo, 90 min occlusion, 24 h reperfusion) of Sprague-Dawley rats. The infarct volume was significantly reduced by 36.6% after the peritoneal injection of ASW (100 mg[sol ]kg) compared with the control. In the immunohistochemical study, ASW markedly inhibited both cyclooxygenase-2 and OX-42 expressions in the penumbral region at 24 h after MCAo. These results suggest that A. senticosus has a neuroprotective effect by inhibiting inflammation and microglial activation in brain ischaemia.
This study evaluated the effect of water extracts of Panax ginseng C.A. Meyer (PG), panaxadiol (PD), panaxatriol (PT), ginsenoside Rb(1), Rb(2), Rc, Rd, Re and Rg(1) on jejunal crypt survival, endogenous spleen colony formation and apoptosis in jejunal crypt cells in gamma-irradiated mice. Jejunal crypts were protected by pretreatment with PG, Rc and Rd. Administration of PG, PD, Rd and Re prior to irradiation resulted in an increase in the formation of endogenous spleen colonies. The frequency of radiation-induced apoptosis in intestinal crypt cells was also reduced by pretreatment with PG, PD, Rb(2), Rc, Rd, Re and Rg(1). In experiments on the effects of the individual ginsenosides, the rank order of activity was Rc > Rd > Rg(1) > Rb(2) > Re > Rb(1) on intestinal crypt survival assay, Re > Rb(2) > Rd > Rg(1) > Rb(1) > Rc on the spleen colony formation assay, and Rg(1) > Re > Rd > Rc > Rb(2) > Rb(1) on inhibiting the death of cells caused by apoptosis. The results indicated that Rc, Rd and Re may have a major radioprotective effect in mice irradiated with high and low doses of radiation. When the same experiments were performed using PD and PT, it was observed that most of the inhibitory effects came from PD rather than PT.
Our previous study demonstrated that the in vivo anti-metastatic effect induced by oral administration of ginseng protopanaxadiol saponins was mediated by their metabolic component M1, and that the growth, invasion and migration of tumor cells were inhibited by M1 but not by ginsenosides. Here we investigated the inhibitory mechanism of M1 on the growth of tumor cells. M1 inhibited the proliferation of B16-BL6 mouse melanoma cells in a time- and dose-dependent manner, with accompanying morphological changes at the concentration of 20 microM. In addition, at 40 microM M1 induced apoptotic cell death within 24 h. Fluorescence microscopy revealed that dansyl M1 entered the cytosol and quickly reached the nuclei (approximately 15 min). Western blot analysis revealed that M1 rapidly up-regulated the expression of p27Kip1, but down-regulated the expression of c-Myc and cyclin D1 in a time-dependent manner. Thus, the regulation of apoptosis-related proteins by M1 is responsible for the induction of apoptotic cell death, and this probably leads to the anti-metastatic activity in vivo.
A homodimeric protein designated quinqueginsin, with a molecular weight of 53 kDa, has been isolated from the roots of American ginseng Panax quinquefolium. It was unadsorbed on DEAE cellulose in low ionic strength and neutral pH, and adsorbed on Affigel blue gel and SP-Sepharose under similar conditions. Its N-terminal sequence bore similarity to those of plant ribosome inactivating proteins and fungal ribonucleases. The protein displayed a variety of biological activities. It possessed ribonucleolytic activity toward yeast tRNA and specific activity toward poly C. It inhibited cell-free translation in a rabbit reticulocyte lysate system with an IC(50) of 0.26 nM, and exerted antifungal action against Fusarium oxysporum, Rhizoctonia solani, and Coprinus comatus. An inhibitory action was expressed toward human immunodeficiency virus-1 reverse transcriptase. This action was potentiated after chemical modification with succinic anhydride.