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Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

Adenocarcinoma↗

Anticarcinogenic effect of red ginseng on the development of liver cancer induced by diethylnitrosamine in rats.

Anticarcinogenic effect of red ginseng (Panax ginseng C.A. Meyer cultivated in JiLin, China) on the development of liver cancer induced by diethylnitrosamine (DEN) in rats was studied, especially in preventive and curative groups. In the preventive group, the rats were given with DEN concomitantly with red ginseng fluid, and in the curative group, the rats were administered with red ginseng fluid after they developed liver cancer nodules induced by DEN. The result of the preventive group revealed that the developmental rate of liver cancer in the experimental group was 14.3%, while 100% in the control group, with the difference being statistically significant. DNA, RNA, glycogen, gamma-GT, SDH, and 5'-NT were maintained at relatively normal level in experimental group, and decreased or increased in the control group. The result of curative group showed that hepatoma nodules of the DEN-red ginseng group I were smaller than those of control group I, the structure of hepatic tissue was well preserved, the area with gamma-GT positive was smaller, and the ultrastructure of hepatocytes was normal. The average life span the DEN-red ginseng group II and the DEN control group II were 72.8 and 42.3 days, respectively. To sum up, all findings on preventive and curative groups had clearly proved that the red ginseng had the anticarcinogenic effect on the development of liver cancer induced by DEN in rats.

Animals↗

Inhibition by ginseng of colon carcinogenesis in rats.

The inhibitory effects of ginseng on the development of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in the colon were investigated in rats. Male, 6-week-old rats were injected with DMH once a week for 4 weeks. Rats in Groups 1 and 2 were fed diets containing red and white ginseng, respectively, at a dose of 1% for 5 weeks, starting one week before the first treatment of DMH. Animals in Groups 3 and 4 received red or white ginseng for 8 weeks starting after DMH treatment. Group 5 served as a carcinogen control group. Numbers of ACF with at least four crypts were significantly reduced in the colon of Group 2 treated with red ginseng combined with DMH. Moreover, rats were injected with DMH 4 times at one-week intervals. They were also fed diets containing 1% red or white ginseng or the control diet throughout 30 days of the experiment. Treatment with red ginseng resulted in a significant decrease of 5- bromo-2'-deoxyuridine labeling indices in colonic crypts comprising ACF. These findings suggest that dietary administration of red ginseng in combination with DMH suppresses colon carcinogenesis in rats, and the inhibition may be associated, in part, with inhibition of cell proliferation, acting on ACF in the colonic mucosa.

1,2-Dimethylhydrazine↗

Panax (ginseng)--panacea or placebo? Molecular and cellular basis of its pharmacological activity.

INTRODUCTION: The use of ethnobotanical drugs amongst Asians as complementary medicine is prevalent and is also gaining increasing popularity in the West. The most well-known herb traditionally used as a drug is the root of the ginseng species. There are many traditional and anecdotal claims to the therapeutic properties of ginseng. In recent years, there have been systematic efforts to analyse the bioactivities of ginseng saponins. METHODS: A comprehensive review of published literature covering molecular and cellular research as well as animal and human studies on ginseng and its derivatives. RESULTS AND CONCLUSION: Current published data would serve as a framework to understand the pharmacology of ginseng in its entirety, from its molecular action to actual therapeutic effects observed in human use. A new paradigm is emerging whereby the pharmacological effects of traditional herbs such as ginseng can be understood in the light of their polyvalent actions as demonstrated by ginseng saponins with their positive anti-mutagenic, anti-cancer, anti-inflammatory, anti-diabetes and neurovascular effects. With increasing understanding, evidence-based incorporation of traditional herbs as complementary medicine into mainstream medical science can be achieved in the near future.

Animals↗

Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Swedish Alternative Medicine Group.

A randomized, multicenter, double-blind, parallel group study was performed to assess the effects of a standardized ginseng extract compared with those of a placebo on quality of life (QoL) and on physiological parameters in symptomatic postmenopausal women. Validated questionnaires [Psychological General Well-Being (PGWB) index, Women's Health Questionnaire (WHQ)] and Visual Analogue (VA) scales were used to assess the effects of the extract on QoL at baseline and after 16 weeks' treatment with either the ginseng extract or placebo. To assess the efficacy of ginseng on postmenopausal symptoms, physiological parameters [follicle-stimulating hormone (FSH) and estradiol levels, endometrial thickness, maturity index and vaginal pH] were recorded at the same time points. Of the 384 randomized patients (mean age 53.5 +/- 4.0 years), the questionnaires were completed by 193 women treated with ginseng and 191 treated with placebo. With regard to the primary endpoint (total score of the PGWB index) the extract showed only a tendency for a slightly better overall symptomatic relief (p < 0.1). Exploratory analysis of PGWB subsets, however, reported p-values < 0.05 for depression, well-being and health subscales in favor of ginseng compared with placebo. No statistically significant effects were seen for the WHQ and the VA scales or the physiological parameters, including vasomotor symptoms (hot flushes). The positive effects of ginseng on health-related QoL in menopausal women should be further investigated. This study shows, however, that the beneficial effects of ginseng are most likely not mediated by hormone replacement-like effects, as physiological parameters such as FSH and estradiol levels, endometrial thickness, maturity index and vaginal pH were not affected by the treatment.

Aged↗

[Effects of subcutaneous injection with different doses of ginseng on the rat model of chronic Pseudomonas aeruginosa pneumonia].

OBJECTIVE: To observe the effect of ginseng extracts on a rat model of chronic Pseudomonas aeruginosa (PA) pneumonia. METHODS: Subcutaneous injection with four different doses of ginseng aqueous extracts to the model rats for two weeks. RESULTS: Milder macroscopic lung pathology and lower incidence of lung abscesses were found in all the four groups received different doses of ginseng treatment compared to the control group (P < 0.05). Histopathology of the lungs was negatively correlated with the ginseng doses (r = -0.95, P < 0.01). The mast cell number in the lung foci in group I, II and IV was significantly lower than that in the control group (P < 0.05). Bacterial clearance in group II and group III was enhanced significantly (P < 0.05) compared with that in the control group. The specific antibody responses were down-regulated in group II, III and IV (P < 0.01), and IgM level in group I was lower compared to the control group (P < 0.01). Serum IgM level was positively correlated with the ginseng doses (r = 0.93, P < 0.05). IgG2a titer in group I was higher than that in the control group (P < 0.05). Serum IgG2a level was positively correlated with the ginseng doses (r = 0.90, P < 0.02). Two weeks after PA lung infection, the serum level of IgG against PA, aeruginosa alginate in group I, II, and III was higher than that in the control and group IV (P < 0.05), and the anti-alginate IgA level in group I, III and IV was lower than that in the control (P < 0.05). CONCLUSIONS: The ginseng dose of 2.5 mg/kg was the best dosage in the present study, and it showed an effect of stimulating T helper type I response.

Animals↗

Modification of radiation response in mice by Panax ginseng and diethyldithiocarbamate.

The aim of this study was to determine the effect of Panax ginseng and its fractions on jejunal crypt survival, endogenous spleen colony formation and apoptosis in jejunal crypt cells of mice irradiated with high- and low-dose of gamma-irradiation. The radioprotective effect of ginseng was compared with the effect of diethyldithiocarbamate (DDC). Ginseng administration before irradiation protected the jejunal crypts (p < 0.005), increased the formation of endogenous spleen colony (p < 0.005) and reduced the frequency of radiation-induced apoptosis (p < 0.05). The radioprotective effect on jejunal crypts and apoptosis in the DDC-treated group appeared similar to that in the ginseng--treated groups. Treatment with DDC showed no significant modifying effects on the formation of endogenous spleen colony. In the experiment on the effect of fractions of ginseng, the result indicated that the lipophilic non-polar compounds (Fraction 1), lipophilic-acidic compounds (Fraction 2), free sugars (Fraction 7) and saponin compounds (Fraction 8) might have a major radioprotective effect. Although the mechanisms of this inhibitory effect remain to be elucidated, these results indicated that ginseng might be a useful radioprotector, especially since it is a relatively nontoxic natural product. Further studies are needed to fully characterize the protective nature of ginseng extract and its components.

Animals↗

[A study on maillard reaction and its products during processing of red ginseng].

OBJECTIVE: To isolate and identify maltol and maltol-3-O-beta-D-glucoside and argininyl-fructosyl-glucoside in red ginseng, and prove that they are products of processing through comparative analysis and artificial synthesis of different products of ginseng. METHOD: Column chromatography, spectral analysis, TLC-scanning quantification, amino acid analysis and artificial synthesis on simulated conditions. RESULT: Maltol and its glycoside are peculiar components in red ginseng, and the content of argininyl-fructosyl-glucoside in red ginseng the product of processing is three times higher than that of white ginseng. CONCLUSION: Maillard reaction exists in the processing of red ginseng, thus proper control of this reaction helps improve the quality red ginseng.

Arginine↗

White, but not Red, Ginseng Inhibits Progression of Intestinal Carcinogenesis in Rats.

Ginseng is a well known traditional medicine in Asian countries which has attracted attention as a potential chemopreventive agent. In the present study, inhibitory effects of white and red ginseng on tumor development were examined using medium-term liver and multi-organ carcinogenicity bioassay systems. No modifying potential of the ginseng preparations were evident in terms of the numbers or areas of glutathione S-transferase placental form (GST-P)-positive foci in rat livers. However, white ginseng, although not its red counterpart, was found to decrease the incidences of adenocarcinoma of the small intestine and colon in the medium-term multi-organ carcinogenesis model, without any affect on the numbers of aberrant crypt foci (ACF). These results indicate that white ginseng may have inhibitory effects on the progression stage of rat intestinal carcinogenesis, but the influence is not strong. Ginseng did not appear to have promoting or inhibitory effects in other organs under the present experimental conditions. Possible application on ginseng for chemoprevention of colon cancer in humans, can be concluded given the lack of obvious adverse effects.

Journal Article↗

[Effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere-telomerase system in K562 cell line].

The aim was to explore the modulating and inhibiting effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere length and telomerase activity in K562 cell line, and to study their anti-tumor mechanism and seek new method of therapy for acute leukemia. Human erythroleukemia cell line K562 was co-cultured with arsenic trioxide, ginseng saponin, beta-elemene separately, cells were collected after 24, 48 and 72 hours for further detecting. Telomere length and telomerase activity were detected by the methods of Southern-blot and PCR-ELISA respectively. The effects of these drugs on telomere length and telomerase activity were observed at different concentrations and length of time. The results showed that (1) telomerase activity of K562 cells decreased after co-cultured with arsenic trioxide, ginseng saponin and beta-elemene. The inhibiting effects depended on drug concentrations and length of time. When co-cultured at proper concentration and period of time, telomerase activity could be inhibited; (2) viability of K562 cells decreased after co-cultured with arsenic trioxide, ginseng saponin and beta-elemene, the inhibiting effect depends on drug concentrations and length of time; (3) after co-cultured with arsenic trioxide, ginseng saponin, and beta-elemene for 72 hours, telomere length of K562 cell line prolonged a little. It is concluded that (1) arsenic trioxide, ginseng saponin and beta-elemene can inhibit telomerase activity in K562 cell line, the suppression of telomerase activity may be one of the mechanisms of anti-tumor effect; (2) arsenic trioxide, ginseng saponin and beta-elemene can inhibit the growth of K562 cell line, the inhibiting effect depends on concentration and time; (3) when telomerase activity was suppressed, the telomere length prolonged a little, indicating that in K562 cell line may exist another mechanism to regulate telomere length, except telomerase activation.

Arsenic Trioxide↗

[Ameliorative effect of ginseng glycopeptide on cross-linking of rat tail tendon collagen].

OBJECTIVE: To investigate the ameliorative effect of ginseng glycopeptide on cross-linking of rat tail tendon collagen. METHOD: ELISA was used to determine the inhibitory effect of ginseng glycopeptide on cross-linking of rat tail tendon collagen in vitro. After ginseng glycopeptide was intraperitoneally administrated to streptozotocin-induced diabetic rats for 12 weeks, the acid solubility, limited pepsin degradation properties and solubility in SDS-2-mercaptoethanol of the rat tail tendon collagen were determined, and the effect of ginseng glycopeptide on the tail tendon collagen cross-linking was evaluated. RESULT: Ginseng glycopeptide inhibited significantly the cross-linking of rat tail tendon collagen in vitro. The solubility of the tail tendon collagen (in acid, pepsin and SDS-2-mercaptoethanol) was markedly decreased in diabetic rats and ginseng glycopeptide-treated diabetic rats had significantly an increase in the collagen solubility in the above-mentioned solutions, suggesting that ginseng glycopeptide decreased severity of the collagen cross-linking. CONCLUSION: Ginsengglycopeptide exhibits an significantly ameliorative effect on cross-linking of rat tail tendon collagen.

Animals↗

Effect of red ginseng on natural killer cell activity in mice with lung adenoma induced by urethan and benzo(a)pyrene.

It was previously reported that red ginseng extract inhibited carcinogenesis by urethan, DMBA, and aflatoxin B1 [Yun et al: Cancer Detect Prevent 1983; 6:515-25]. In an attempt to investigate the mechanism of the anticarcinogenic effect of ginseng, the natural killer (NK) activity and the incidence of lung adenoma were followed over a period of 48 weeks postinjection with urethan or benzo(a)pyrene. The NK activity was markedly depressed from 4 weeks to 24 weeks after injection of carcinogens. This decreased NK activity was returned to the level of controls by administration of ginseng. At the same time, a lower incidence of lung adenoma was noted following administration of ginseng to urethan-injected mice. However, the lung adenoma induced by benzo(a)pyrene began to occur at 48 weeks in which NK activity had naturally declined to a level too low to be affected by ginseng, and administration of ginseng did not decrease the incidence. In conclusion, these results suggest that the anticarcinogenic effect of ginseng may be related to the augmentation of NK activity.

Adenoma↗

Ginseng-enhanced oxidative and phagocytic activities of polymorphonuclear leucocytes from bovine peripheral blood and stripping milk.

This study investigated the effect of a dried ginseng extract on polymorphonuclear leucocytes (PMNL) in bovine blood and milk. In a test for chemiluminescence (CL), PMNL were pre-incubated in ginseng solution at 37 degrees C in 5% CO2 for 60 min, and then stimulated with bovine serum opsonized zymosan. The CL was about 30% higher for the cells pre-treated with ginseng solutions 100-1,000 micrograms/ml as compared with the non-ginseng-treated cells. In a test for phagocytosis, PMNL and fluorescent microspheres were incubated with ginseng in RPMI-1640 supplemented with 10% bovine serum at 37 degrees C for 60 min. The proportion of actively phagocytic cells in the ginseng-treated group was greater than that in the non-ginseng treated group.

Animals↗

Ginseng treatment enhances bacterial clearance and decreases lung pathology in athymic rats with chronic P. aeruginosa pneumonia.

In an athymic rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied the effects of the Chinese herb ginseng. Rats were treated subcutaneously with ginseng extracts (25 mg/kg) once a day for 10 days after challenge with P. aeruginosa embedded in alginate beads. We found that ginseng treatment significantly reduced bacterial load (p < 0.02) and the number of mast cells in the lungs (p < 0.01). Furthermore, it decreased the severity of lung pathology (p < 0.02) and lowered serum anti-P. aeruginosa IgM and IgA antibody levels (p < 0.004, p < 0.04) compared to the control group. The down-regulated specific humoral immunity in the ginseng-treated group and the fact that athymic rats have a severely compromised T-cell-mediated immune reactivity due to the absence of thymus might suggest an activation of innate immunity after ginseng treatment. Our findings indicate that ginseng treatment increases the resistance of the athymic rats to P. aeruginosa lung infection. We therefore think that ginseng has promising potential as a natural medicine for stimulation of the immune system in CF patients with chronic P. aeruginosa lung infections.

Adjuvants, Immunologic↗

Panax ginseng reduces adriamycin-induced heart failure in rats.

The purpose of this study was to investigate the protective effects of Panax ginseng on adriamycin-induced heart failure. Wistar rats were divided into four groups: control, adriamycin, ginseng and adriamycin with ginseng. Adriamycin (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks. Ginseng was administered via an oral feeding tube once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5 week post-treatment period, the hearts of the rats were used to study the synthesis rates of DNA, RNA and protein, myocardial antioxidants and lipid peroxidation. At the end of 3 weeks treatment, heart failure was characterized by ascites, congested liver and depressed cardiac function. Nucleic acid as well as protein synthesis was inhibited, lipid peroxidation was increased and myocardial glutathione peroxidase activity was decreased indicating adriamycin-induced heart failure. In contrast, the administration of ginseng, before and concurrent with adriamycin, significantly attenuated the myocardial effects, lowered the mortality as well as the amount of ascites, increased in myocardial glutathione peroxidase, macromolecular biosynthesis and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation. These findings indicated that ginseng may be partially protective against adriamycin-induced heart failure.

Animals↗

Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in ICR mice.

Ginseng is a shade-loving perennial herb that is cultivated mainly in Korea, Japan, and China. The ginseng root has been used as a tonic remedy, and its antidiabetic activity has been demonstrated as early as 1920s. Although wild ginseng was anecdotally thought to be superior to cultivated ginseng as far as pharmacological properties were concerned, there have been no prior reports on the antidiabetic effect of wild ginseng. In this study, we investigated the preventative anti-diabetic and anti-obese effects of wild ginseng ethanol extract (WGEE). In the preventive experiment, WGEE co-administered with a high fat diet significantly inhibited body weight gain, fasting blood glucose, triglyceride, and free fatty acid levels in a dose dependent manner. WGEE-treated mice at doses of 250 and 500 mg/kg improved the insulin resistance index by 55% and 61% compared to the high fat diet (HFD) control, respectively. Diameters of white and brown adipocytes were also decreased by 62% and 46% in the WG500-treated group compared to those in HFD fed control mice. Taken together, WGEE has potential as a preventive agent for type 2 diabetes mellitus (and possibly obesity) and deserves clinical trial in the near future.

Adipose Tissue↗

The memory-enhancing effects of Ginseng and Ginkgo biloba in healthy volunteers.

RATIONALE: The use of herbal remedies, such as Ginkgo biloba and Ginseng, for improving cognitive performance has become increasingly popular during recent years. Several previous studies have indicated that administration of Ginkgo biloba and Ginseng may improve aspects of learning and memory in healthy volunteers. These results, however, are generally not supported by well-controlled clinical studies. Also, positive results have often been reported from studies investigating effects related to short-term, chronic administration of the extract. Nonetheless, both Ginkgo biloba and Ginseng are marketed as having the capacity to enhance cognitive functions, such as memory and learning, in the long term. OBJECTIVE: This study aimed at investigating whether the use of Ginkgo biloba and Ginseng for a long period of time has positive effects on performance on learning and memory. METHODS: Community-dwelling volunteers ( n=3500) from The Betula prospective cohort study: memory, health, and aging were included in the study. RESULTS: It was found that the use of neither Ginkgo biloba ( n=40) nor Ginseng ( n=86) was associated with enhanced memory performance in any of the eight memory tests examined, relative to control groups either using or not using nutritional supplements. CONCLUSIONS: These findings indicate that use of Ginkgo biloba or Ginseng does not provide any quantifiable beneficial effects on memory performance in the long-term in healthy adult volunteers.

Adult↗

The efficacy of ginseng. A systematic review of randomised clinical trials.

OBJECTIVE: Ginseng is one of the most popular herbal remedies, and a number of health claims are made for it. This systematic review provides an evaluation of the current evidence for or against the efficacy of ginseng root extract. METHODS: Searches of the computerised literature databases Medline, Embase, Biosis, CISCOM and the Cochrane Library were performed to retrieve double-blind, randomised, placebo-controlled trials of ginseng root extract for any indication. Manufacturers and experts were contacted to provide additional information. There were no restrictions regarding the language of publication. The outcome and methodological quality of all trials were independently assessed by two reviewers. RESULTS: Sixteen trials met the inclusion criteria and were reviewed. These trials related to physical performance, psychomotor performance and cognitive function, immunomodulation, diabetes mellitus and herpes simplex type-II infections. The evidence found for ginseng root extract is compelling for none of these indications. CONCLUSION: Based on these data, it is concluded that the efficacy of ginseng root extract is not established beyond reasonable doubt for any of these indications. The widespread use of ginseng as a herbal remedy warrants more rigorous investigations to assess its efficacy and safety.

Adjuvants, Immunologic↗