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Panax ginseng as a potential immunomodulator: studies in mice.

There has been continuing interest in the development of synthetic and natural compounds which modify the immune response, particularly for the treatment of AIDS and cancer. Panax ginseng, employed for its putative medicinal properties in South Asia, was examined for its immunomodulatory properties in mice. A systematic evaluation of multiple immune system components revealed that Panax ginseng stimulated basal natural killer (NK) cell activity following subchronic exposure and helped stimulate recovery of NK function in cyclophosphamide-immunosuppressed mice but did not further stimulate NK activity in poly I:C treated mice. Other immunological parameters examined, including T and B cell responses were not affected. Panax ginseng provided a degree of protection against infection with L. monocytes but did not inhibit the growth of transplanted syngeneic tumor cells. Increased resistance to L. monocytogenes was not detected in challenged mice previously given immunosuppressive doses of cyclophosphamide. Taken together, these data suggest that Panax ginseng has some immunomodulatory properties, primarily associated with NK cell activity.

Adjuvants, Immunologic↗

[The modulating effect of panax pseudoginseng wall saponins on the DAG-PKC signal pathway and TNF secretion of macrophages].

OBJECTIVE: To explore the roles of panax pseudoginseng wall saponins on the DAG-PKC signal pathway and TNF secretion of macrophages. METHODS: The changes of the activities of postburn inositol lipid signal system factors such as PLC, DAG, cytomembrane PKC, cytoplasma PKC, and intracellular calcium concentration and the secretory amount of macrophage TNF were observed. RESULTS: Panax pseudoginseng wall saponins could reduce the increased PLC activity from 57.58 +/- 8.19 to 27.00 +/- 2.31 and the intracellular calcium concentration from 393.18 +/- 392.62 to 90.56 +/- 7.21. With the role of panax pseudoginseng wall saponins, DAG activity reduced from 488.10 +/- 40.20 to 288.30 +/- 30.00, cytomembrane PKC activity decreased from 3081.50 +/- 698.50 to 1699.50 +/- 218.50, and cytoplasmic PKC activity from 2 188.60 +/- 258.30 to 848.40 +/- 138.30. The secretory TNF amount of macrophage decreased by 55%. CONCLUSION: Panax pseudoginseng wall saponins might play an very important role in the modulating of the DAG-PKC signal pathway and decreased TNF secretion of macrophage.

Animals↗

[A study on the rotation of crops among Panax quinquefolium, Perilla frutescens and Coix lacryma-jobi].

OBJECTIVE: To provide evidence for establishing an efficient method of growing Panax quinquefolium by rotation of crops. METHOD: Four-year old P. quinquefolium was cultivated in water and soil cultures. Biological assays were conducted with the aqueous extracts of P. quinquefolius, Fructus Perillae and roots of Coix lacryma-jobi. P. quinquefolium was cultivated in the soil where purple Perilla frutesens and C. lacryma-jobi were grown previously. The effects of rotation were determined. RESULT: The stems, leaves and fibrous roots of Panax quinquefolium contained allelopathic substances. When the concentration of the allelopathic substances exceeded 1g per kg soil, P. quinquefolius could not grow. On the other hand, when the concentration of allelopathic substances fell below 0.2 g per kg soil, the rate of seedling growth was decreased by 25%. When P. quinquefolius was cultivated in the soil in which purple Perilla frutesens had previously grown, or in the soil supplemented with Fructus Perillae, the rates of seedling growth and the yield were raised by 26.8% and 11.5% tively, in comparison with the controls. CONCLUSION: Rotation of Panax quinquefolium and Perilla frutesens was shown to be a good way for the cultivation of the former. During the growing process, application of Fructus Perillae to the soil could further enhance the growth and of Panax quinquefolium.

Agriculture↗

[Principal component analysis and cluster analysis of inorganic elements in Panax quinque folium. L].

The contents of elements such as Mg, Al, P, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd and Pb in twelve Panax quinque folium. L samples were determined by means of ICP/MS. The results were used for the development of element fingerprint chromatogram. The principal component analysis of SPSS was applied for the study of characteristic elements in Panax quinque folium. L. Five principal components which accounted for over 90% of the total variance were extracted from the original data. The analysis results show that Fe, Al, V, Mn, Mg, Sr, Mo, Ca and Cu may be the characteristic elements in Panax quinque folium. L. The results of Q-type cluster analysis show that the samples could be clustered reasonably into five groups, and the elemental distribution characteristics are related to the breeds of Panax quinque folium. L.

Cluster Analysis↗

[Observation of therapeutic effect by combined administration of Salvia miltiorrhiza, ligustrazine and Panax notoginseng on late hemorrhagic shock of rabbits].

OBJECTIVE: To explore the therapeutic mechanism of Salvia miltiorrhize, ligustrazine and Panax notoginseng in treating late hemorrhagic shock in rabbit. METHODS: Rabbit hemorrhagic shock models (MPA 5.3 kPa) were set up according to Wiggers' method and administrated Salvia miltiorrhiza, ligustrazine, Panax notoginseng. The values of blood RBC superoxide dismutase (SOD) and blood lactate (BL), plasma malondialdehyde (MDA) and magnesium (Mg++) were continuously monitored before shock, 120 minutes after shock, 60 and 120 minutes after hydraulic dilatation. RESULTS: (1) In 120 minutes after shock, the level of SOD decreased and the concentrations of MDA, BL, Mg++ were markedly increased, which indicated that the cell membrane damage caused by oxygen free radicals in rabbit hemorrhagic shock. (2) Salvia miltiorrhiza, Ligustrazine or Panax notoginseng could alleviate lipidperoxidation injury to tissue. Compared with the single drug administration groups, the effects of oxygen free radicals scavangers by combined administration with half dose of 2 drugs were better than the single drug with full dose alone and the side effects such as depression of blood pressure and heart rates would be alleviated. CONCLUSION: Combined administration of Salvia miltiorrhiza, ligustrazine and Panax notoginseng would half the dosage, the blood pressure depression and heart rate reduction alleviated and better result obtained.

Animals↗

Phylogeny of Panax using chloroplast trnC-trnD intergenic region and the utility of trnC-trnD in interspecific studies of plants.

Sequences of the chloroplast trnC-trnD region and the internal transcribed spacer (ITS) regions of nuclear ribosomal DNA were obtained for all species of Panax L. (the ginseng plant genus, Araliaceae) to reconstruct phylogenetic relationships. The trnC-trnD phylogeny is congruent with the ITS phylogeny for the diploid taxa of Panax. This study is the first use of the trnC-trnD sequence data for phylogenetic analysis at the interspecific level. We evaluated this DNA region for its phylogenetic utility at the lower taxonomic level for flowering plants. The trnC-trnD region includes the trnC-petN intergenic spacer, the petN gene, the petN-psbM intergenic spacer, the psbM gene, and the psbM-trnD intergenic spacer. The petN and psbM genes are small, 90 and 104-114 bp across angiosperms, respectively, and have conserved sequences. We have designed universal amplification and sequencing primers within these two genes. Using these primers, we have successfully amplified the entire trnC-trnD region for a diversity of flowering plant groups, including Aralia L. (Araliaceae), Calycanthus L. (Calycanthaceae), Corylus L. (Betulaceae), Hamamelis L. (Hamamelidaceae), Hydrocotyle L. (Apiaceae), Illigera Blume (Hernandiaceae), Nelumbo Adans. (Nelumbonaceae), Nolana L. ex L.f. (Solanaceae), Prunus L. (Rosaceae), and Staphylea L. (Staphyleaceae). In Panax, the trnC-trnD region provides a similar number of informative phylogenetic characters as the ITS regions and a slightly higher number of informative characters than the chloroplast ndhF gene. We thus demonstrate the utility of the trnC-trnD region for lower-level phylogenetic studies in flowering plants.

Chloroplasts↗

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↗

Panax ginseng protects the testis against 2,3,7, 8-tetrachlorodibenzo-p-dioxin induced testicular damage in guinea pigs.

OBJECTIVES: To investigate histopathologically the beneficial effects of Panax ginseng extract on guinea pig testes damaged by 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD). MATERIALS AND METHODS: Ninety guinea pigs were divided into six equal groups. The normal controls (group 1) received vehicle and saline; group 2 received TCDD (1 microgram/kg) intraperitoneally; group 3 and 4 received 100 or 200 mg/kg per day of Panax ginseng water extract (PG-WE) intraperitoneally for 28 days from 1 week before TCDD injection; groups 5 and 6 received PG-WE for 14 days from 1 week after TCDD treatment. RESULTS: The gain in body weight was less in groups treated with TCDD than in controls. Moreover, the body weight of group 2 decreased from 14 days after TCDD exposure, while that of groups 3 and 4 increased; there was no decrease in body weight in groups 3-6. The decrease in testicular weight caused by TCDD was prevented by PG-WE. Light microscopy showed smaller tubules and late maturation arrest in group 2; electron microscopy showed a dissolution of the germinal epithelium, disrupted tight junctions between adjacent Sertoli cells, and altered germ cells at all developmental stages. The maturation arrest in germ cells caused by TCDD was ameliorated in groups 3-6. The testes almost completely recovered in groups 3 and 4 and there was some therapeutic effect of PG-WE in groups 5 and 6. CONCLUSIONS: These results confirm the protective and therapeutic effects of Panax ginseng on atrophy and testicular damage induced by TCDD, providing evidence that ginseng might be a useful agent in preventing and treating testicular damage induced by environmental pollutants.

Animals↗

Panax vietnamensis protects mice against carbon tetrachloride-induced hepatotoxicity without any modification of CYP2E1 gene expression.

In order to explore the effect of Panax vietnamensis on carbon tetrachloride-induced hepatotoxicity, mice were pretreated for 7 days with either crude extract or total saponins. Crude extract and total saponins dramatically decreased carbon tetrachloride-induced increase of serum GST alpha level (-50.0%, -49.5% respectively). Serum AST level was significantly decreased only with total saponins (-52.2%) and ALT level was slightly modified. In vitro experiments shown that both preparations at high concentrations (> 2000 micrograms/ml) are able to inhibit CYP2E1 enzymatic activity in mouse and human microsomes. However, we did not observe any modification of Cyp2e1 gene expression (enzymatic activity, protein and mRNA levels) in mice treated with either crude extract or total saponins. Taken together, these data demonstrated that Panax vietnamensis could be used as an hepatoprotectant. However, the mechanism of action is not associated with CYP2E1 expression, as previously suggested in vitro in rat for total saponins from Panax ginseng.

Animals↗

Phylogenetic relationship in the genus Panax: inferred from chloroplast trnK gene and nuclear 18S rRNA gene sequences.

Chloroplast trnK gene and nuclear 18S rRNA gene sequences of 13 Panax taxa, collected mainly from Sino-Japanese floristic region, were investigated in order to construct phylogenetic relationship and to assist taxonomic delimitation within this genus. The length of trnK gene sequence varied from 2537 bp to 2573 bp according to the taxa, whereas matK gene sequences, embedded in the intron of trnK gene, were of 1512 bp in all taxa. Species-specific trnK/ matK sequence provided much insight into phylogeny and taxonomy of this genus. 18S rRNA gene sequences were of 1808 or 1809 bps in length, only 9 types of 18S rRNA sequences were observed among 13 taxa. Parsimony and neighbor-joining analyses of the combined data sets of trnK-18S rRNA gene sequences yielded a well-resolved phylogeny within genus Panax, where three main clades were indicated. P. pseudoginseng and P. stipuleanatus formed a sister group located at a basal position in the phylogenetic tree, which suggested the relatively primitive position of these two species. Monophyly of P. ginseng, P. japonicus (Japan) and P. quinquefolius, which are distributed in northern parts of Asia or America, was well supported (Northern Clade). The remaining taxa distributed in southern parts of Asia formed a relatively large clade (Southern Clade). The taxonomic debated taxa traditionally treated as subspecies or varieties of P. japonicus or P. pseudoginseng showed various nucleotide sequences, but all fell into one cluster. It might suggest these taxa are differentiated from a common ancestor and are in a period of high variation, which is revealed not only on morphological appearance, but also on molecular divergence. By comparing trnK and 18S rRNA gene sequences among 13 Panax taxa, a set of valuable molecular evidences for identification of Ginseng drugs was obtained.

Cell Nucleus↗

Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity.

Single doses of the traditional herbal treatment Panax ginseng have recently been shown to elicit cognitive improvements in healthy young volunteers. The mechanisms by which ginseng improves cognitive performance are not known. However, they may be related to the glycaemic properties of some Panax species. Using a double-blind, placebo-controlled, balanced crossover design, 30 healthy young adults completed a 10 min test battery at baseline, and then six times in immediate succession commencing 60 min after the day's treatment (placebo, 200mg G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction task (2 min); a Serial Sevens task (2 min); a Rapid Visual Information Processing task (5 min); then a 'mental fatigue' visual analogue scale. Blood glucose was measured prior to each day's treatment, and before, during and after the post-dose completions of the battery. Both the 200mg and 400mg treatments led to significant reductions in blood glucose levels at all three post-treatment measurements (p 0.005 in all cases). The most notable behavioural effects were associated with 200mg of ginseng and included significantly improved Serial Sevens subtraction task performance and significantly reduced subjective mental fatigue throughout all (with the exception of one time point in each case) of the post-dose completions of the 10 min battery (p 0.05). Overall these data suggest that Panax ginseng can improve performance and subjective feelings of mental fatigue during sustained mental activity. This effect may be related to the acute gluco-regulatory properties of the extract.

Adult↗

Panax ginseng: a role in cancer therapy?

Panax ginseng is a plant that has been used in traditional medicine in China for thousands of years. It is used as a general tonic or adaptogen with chronically ill patients and is frequently featured in traditional medicine prescriptions from China, Japan, and Korea used by cancer patients. The putative active compounds are the ginsenosides, of which there are more than two dozen. These compounds are found in both Panax ginseng and in other Panax species that are used in herbal medicine. Analysis of ginsenosides is being used in developing quality control assessments for ginseng, which has frequently been adulterated due to its high cost; many currently available standardized extracts do appear to contain the amounts of ginsenosides listed on package labeling. The toxicity of ginseng appears to be low: some of the reports of toxic episodes of ginseng may actually pertain to other components of multicomponent preparations. Very low incidence of toxicity has been observed in ginseng clinical trials using well-characterized preparations. Numerous pharmacological activities of ginseng and the ginsenosides have been explored: the authors review here the activities relating to cancer. Immune system modulation, antistress activities, and antihyperglycemic activities are among the most notable features of ginseng noted in laboratory and clinical analyses. Much testing has been done in humans to explore ginseng's purported antifatigue properties, but this area remains controversial. A number of investigations point to antitumor properties and other pharmacological activities related to cancer, but no trials have yet confirmed a clinically significant anticancer activity. Cancer patients may empirically find ginseng to be useful when they are fatigued, although clinical trials should be conducted to confirm its benefits.

Female↗

Molecular authentication of Panax ginseng species by RAPD analysis and PCR-RFLP.

In order to develop convenient and reproducible methods for the identification of ginseng drugs at a DNA level, randomly amplified polymorphic DNA (RAPD) and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses were applied within Panax species. To authenticate Panax ginseng among ginseng populations, RAPD analysis was carried out using a 20 mer-random primer. The similarity coefficients among the DNA of ginseng plants analyzed were low, ranging from 0.197 to 0.491. In addition, by using PCR-RFLP analysis, very different fingerprints were obtained within Korean ginseng plants. These results suggest that these methods are able to authenticate the concerned Panax species. Broader application of this approach to authenticate other morphologically similar medicinal materials is rationalized.

DNA, Plant↗

Effect of Panax ginseng on age-related changes in the spontaneous motor activity and dopaminergic nervous system in the rat.

Effects of Panax ginseng on the spontaneous motor activity and central dopaminergic systems in old rats were investigated and compared with those in young rats. Oral intake of a 1.8% water extract of Panax ginseng for four weeks produced an increase in spontaneous motor activity during the dark period in old rats, while it caused a decrease in the activity in young rats. After the intake of ginseng extract for five weeks, it caused a significantly low dopamine utilization in the daytime in the striatum of old rats, while it produced a high dopamine utilization in the structure of young rats. Concentrations of striatal dopamine D-2 receptors in old rats were significantly lower than that in young rats, although subchronic Panax ginseng did not affect the striatal D-1 and D-2 receptors of old rats. These results suggest that subchronic intake of ginseng extract inhibits the activity of nigro-striatal dopamine neurons in the daytime and activates spontaneous motor activity during the dark period in old rats, while it produces opposite effects in young rats.

Aging↗

[Inhibiting effects of Panax notoginseng extracts on proliferation of GES-1 cells and MNNG-transformed GES-1 cells].

OBJECTIVE: Through cell cultivation, we studied the inhibiting effects of the serum of the dog fed with Panax notoginseng extracts on precancerous gastric cells, trying to find the best time points or periods when the extracts' function was the strongest after administration of the extracts to the dog. METHODS: The experiments adopted eternalized human gastric mucosa epithelium GES-1 cells and MC cells gained from GES-1 cells transformed by N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) as the model of precancerous lesions for study in vitro. We took the serum of a dog before and at different points of time after feeding the dog with Panax notoginseng extracts for experiment. By means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, we examined the inhibiting effects of the serum after culturing the GES-1 and MC cells for 72 hours with different concentration (8%, 4%, 2%) of medicated serum obtained from the dog at different points of time, so as to find that, at which points of time the medicated serum obtained, it would be the most effective. RESULTS: The results showed that the GES-1 and MC cells inhibition rates of medicated serum from the points of 2-hour and 6-hour were the highest, and the culture medium containing 8% of medicated serum from these two points had prominent inhibiting effects on both kinds of cells. The GES-1 cells inhibition rate in culture medium containing 8% of medicated serum from the point of 2-hour was 70.8% (P<0.01) and that of the MC cells was 45.3% (P<0.01). The GES-1 cells inhibition rate in culture medium containing 8% of medicated serum from the point of 6-hour was 88.5%(P<0.01) and that of the MC cells was 42.4% (P<0.01). CONCLUSION: The points of time with the strongest inhibiting effects are 2 hours and 6 hours after being fed with Panax notoginseng extracts. At these two points, the serum is most effective in inhibiting the proliferation of GES-1 and MC cells.

Animals↗

[Apoptosis-promoting effect of Panax notoginseng extracts on MNNG-transformed GES-1 cells].

OBJECTIVE: To study the apoptosis-promoting effect of the serum from Panax notoginseng extracts-fed dog on precancerous gastric cells by means of flow cytometry. METHODS: In the experiment, we adopted eternalized human gastric mucosa epithelium GES-1 cells transformed by N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) (MC cells) as the model of precancerous lesions for study in vitro. We took the serum of a dog before and at two different points of time (2 and 6 hours) after feeding the dog with Panax notoginseng extracts for experiment. The MC cells were cultured in mediums with different concentrations of the medicated serum at 2- or 6-hour point of time for 72 hours. By means of flow cytometry, we examined the apoptosis-promoting effects of the serums on the MC cells. RESULTS: The medicated serums at these 2 points of time had significant effects in promoting MC cell apoptosis. The proportions of apoptotic cells in culture mediums with medicated serums had a significant increase as compared with those in culture mediums with non-medicated serums (serum obtained before administration of extracts to the dog) under the same conditions (P<0.05). The number of MC cells in G(0)/G(1)phase was decreased (P<0.05) and that in G(2)/M phase increased (P<0.05), while no consistent changes were observed in S phase. CONCLUSION: The medicated serums obtained at the two different points of time have significant apoptosis-promoting effects on MC cells. They decrease the number of MC cells in G(0)/G(1) phase and increase the number of MC cells in G(2)/M phase. This is probably responsible for the effects of Panax notoginseng extracts in inhibiting the proliferation of MC cells and promoting its apoptosis.

Animals↗

[Effects of ethanol extracts of Panax notoginseng on liver metastasis of B16 melanoma grafted in mice].

OBJECTIVE: To observe the effects of ethanol extracts of Panax notoginseng on the tumor and the liver metastasis in experimental mice grafted with B16 melanoma. METHODS: B16 melanoma was transplanted in the spleen of C57BL/6 mice. The effects of different doses of ethanol extracts of Panax notoginseng on the inhibition rate of spleen tumors and the liver metastasis were observed respectively. RESULTS: The high-, medium-, and low-doses of the extracts and the interferon-alpha (IFN-alpha) can improve the quality of life of the experimental mice. The weights of spleen tumor were lower in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the normal saline (NS)-treated group (P<0.05 or P<0.01). The liver metastasis was less in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the NS-treated group (P<0.01). CONCLUSION: The ethanol extracts of Panax notoginseng can improve the quality of life of the experimental mice and inhibit the growth of tumor and the liver metastasis.

Animals↗

[Determination of six ginsenosides in Panax species by high performance liquid chromatography].

A method for the determination of six major ginsenosides in panax species by high performance liquid chromatography (HPLC) with UV detection at 203 nm is described. The six major ginsenosides, which were reported to account for more than 90% of the total ginsenosides content of the panax species' root, were successfully separated using gradient HPLC. The column to be used was a Cosmosil-C18 reversed-phase, 4.6 mm i.d. x 250 mm, 5 microns (Japan), connected with a C18 guard column and the mobile phase was acetonitrile and water. The calibration curves of the six ginsenosides were all linear over the range of 25 mg/L-300 mg/L with good correlation coefficients (> 0.99). The recoveries for the ginsenosides were all above 80%. For real samples and recovery study, the major ginsenosides were ultrasonically extracted by methanol. The extracts were evaporated to 1 mL, under vacuum, at about 50 degrees C and then diluted by methanol. Just prior to HPLC analysis, the sample solutions were filtered using a C18 cartridge. This method has been successfully applied to the analysis of four commercial panax samples.

Chromatography, High Pressure Liquid↗