• YAKHAK HOEJI
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• v.46 no.2
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• pp.113-119
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• 2002

The composition of monosaccharides of acidic polysaccharide isolated from ethanol-insoluble and water-soluble fractions of red ginseng roots was analysed and its immunological activities were investigated. Red ginseng acidic polysaccharide (RGAP) was composed of glucose (26.1 mole %), arabinose (1.6 mole %), glucuroninc acid (51.8 mol %) and galacturonic acid (5.1 mole %) as determined by gas liquid chromatography. Addition of RGAP increased production of nitric oxide (NO) and tumor necrosis factor (TNF)-$\alpha$ in the rodent macrophage cultures. Peritoneal macrophages from RGAP-treated mice exhibited potent tumoricidal activities toward P815 and WEHI 164 tumor cells. It was also observed that concentrations of NO and TNF-$\alpha$ were high in the culture medium of macrophages from the mice administered with RGAP. Moreover, treatment of RGAP in vivo stimulated tumoricidal activities of natural killer (NK) cells. Treatment with RGAP increased life span of sarcoma 180-bearing mice and decreased tumor weights of B16-tumor-bearing mice. These results suggest that activation of macrophages and NK cells serve to enhance in vivo anticancer activities of RGAP.

• Natural Product Sciences
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• v.6 no.1
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• pp.31-35
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• 2000

Effects of red ginseng acidic polysaccharides (RGAP) on immune system were studied. The proliferation of spleen cells was induced by RGAP treatment per se. Cotreatment of lipopolysaccharide $(100\;{\mu}g/ml)$ or concanavalin A $(1\;{\mu}g/ml)$ with RGAP further stimulated the spleen cell proliferation. BALB/c mice treated with RGAP showed a slight splenic hyperplasia and increased antibody forming cell response to sheep red blood cells. Flow cytometry analysis revealed an influx of macrophages in the mice treated with RGAP.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.5
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• pp.752-757
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• 2003

This study was carried out in order to develop the method for isolation of red ginseng acidic polysaccharide (RGAP) haying immunomodulating antitumor activity from red ginseng by-product. The red ginseng by-product was obtained from red ginseng residues produced in processing of red ginseng ethanol extract. The yield of RGAP isolated by ultrafiltration was 20.9%. The active substance (GFP) was purified by DEAE-sepharose column chromatography RGAP induced nitric oxide (NO) exhibited tumoricidal activities against P8l5 (mastocytoma) tumor cells. Acid-hydrolyzed RGAP fragments were shown four to five spots. These sopts showed the same R$_{f}$ values with sugars designated as rhamnose, glucose, glactose and glucuronic acid. Some physico-chemical properties of RGAP were investigated. pH and dry reduction content at 105$^{\circ}C$ were 4.74 and 4.72%, respectively. Crude protein, ash and Pb contents were 3.30%, 4.74% and 2.30 ppm. These results suggest that we will be able to produce RGAP from red ginseng by-product by ultrafiltration in a large scale.e.

• Journal of Ginseng Research
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• v.33 no.2
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• pp.99-103
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• 2009

The in-vitro immunomodulatory function of murine natural-killer (NK) cells induced by red-ginseng acidic polysaccharide (RGAP) in ovariectomized (OVX) rats was examined in this study. The IL-2-induced NK cell activity was significantly decreased in the OVX rats compared to the sham groups, but the normally induced NK cell activity was not. RGAP, however, increased the NK cell activity in both groups, and this effect involved iNOS expression. The inhibition of iNOS activity did not increase the NK cell cytotoxicity by RGAP in the OVX rats. The data that were obtained also demonstrated that the expression of iNOS was increased in the spleen of the OVX rats. These results indicate that RGAP increases the tumoricidal activity of the NK cell in the OVX rats, which is a primed or activated state of innate immune cells resulting from the changes in cytokine production induced by estrogen-deficient stress. Therefore, RGAP has a synergistic effect on the NK cell activities, which are regulated by the iNOS signals in OVX rats. This suggests that RGAP is useful for potential therapeutic strategies as a nutrient in regulating the NK cells in OVX rats.

• Toxicological Research
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• v.19 no.3
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• pp.173-180
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• 2003

The present study was conducted to investigate the single and 2-week repeated dose toxicity of red ginseng acidic polysaccharide (RGAP) in Sprague-Dawley rats. The test article was administered orally to rats at dose levels of 0, and 2000 mg/kg/day for single dose toxicity study and at dose levels of 0, 250, 500, and 1000 mg/kg/day for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated RGAP. Based on these results, it was concluded that the 2-week repeated oral dose of RGAP may have no toxic effect in rats at a dose level of 1000 mg/kg/day. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both sexes.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.73-78
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• 2008

Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C.A. Meyer), has been shown to have a variety of biological functions such as immunostimulating and anti-tumor activities. In the present study, we investigated whether RGAP inhibited ligand-induced platelet aggregation. The washed platelet-rich plasma was prepared from male SD rats with successive centrifugation. The platelets $(10^8/ml)$ were preincubated with 1 mM of $CaCl_2$ for 2 min either in the presence or in the absence of RGAP $(10{\sim}50\;{\mu}g/ml)$ and were stimulated with collagen (2.5 ${\mu}g/ml$) and thrombin (0.1 U/ml). RGAP dose-dependently inhibited thrombin-induced platelet aggregation with $IC_{50}$ value of $26.2{\pm}2.0$ ${\mu}g/ml$. In collagen-induced platelet aggregation, RGAP inhibited the reaction with an $IC_{50}$ value of $31.5{\pm}3.0\;{\mu}g/ml$. RGAP potently suppressed the intracellular calcium ion, which was stimulated by thrombin (0.1 U/ ml). Among mitogen-activated protein kinase (MAPK) subtypes, the extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK were analyzed in the present study. RGAP inhibited the phosphorylation of ERK2 and p38 MAPK, which was activated by collagen (2.5 ${\mu}g/ml$). Finally, these results suggested that besides saponin fraction, RGAP take an important role in the preventive effect of Korean red ginseng against cardiovascular disease such as thrombosis and atherosclerosis.

• Natural Product Sciences
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• v.10 no.6
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• pp.284-288
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• 2004

We have recently reported that red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C. A. Meyer), showed immunomodulatory antitumor activities, mainly mediated by nitric oxide (NO) production by macrophage. In this study, we examined the effect of RGAP on anticancer activity using lung carcinoma 3LL, sarcoma 180 and adenocarcinoma JC tumor cells transplanted into mice as well as antimetastatic activity using B16-F10 melanoma. When RGAP (300 mg/kg) were treated to mice implanted with one of the three kinds of tumor cells, the tumor weight significantly decreased compared with control mice. Tumor inhibition ratios of RGAP (300 mg/kg) in mice transplanted with lung carcinoma 3LL, sarcoma 180 and adenocarcinoma JC cells were 26.8%, 29.3% and 31.6%, respectively. Hundred mg/kg of RGAP did not cause a significant decrease in tumor weight compared with control group. When RGAP was administered i.p. with the dose of 100 and 300 mg/kg in B16-F10 melanoma-bearing mice, lung metastasis were reduced significantly in mice. Corrected phagocytic index was also remarkably increased by RGAP. These results suggest that stimulation of phagocytic activity of macrophages may be a mechanism for in vivo anticancer and antimetastasis activities of RGAP.

• Journal of Ginseng Research
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• v.29 no.4
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• pp.176-181
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• 2005

Our previous reports demonstrated that ip. administration of Korean red ginseng acidic polysaccharide (RGAP) exerts antitumor activity In mice. The present study was carried out to compare the effects of ip. and p.o. routes of administration of RGAP on either normal or tumor-bearing BALB/c mice. RGAP was administered either ip. or p.o. at doses of 100, 300, 500, 1000 mg/kg for 1 or 5 weeks. Peritoneal macrophages from mice treated with RGAP p.o. at a dose of 300 mg/kg either for 1 or 5 weeks did not exhibit growth inhibition activity toward WEHI-I64 tumor cells. However, administration of RGAP at a dose of 600 mg/kg for both 1 and 5 weeks increased the antitumor activity of macrophages. Oral administration of RGAP (600 mg/kg) for 5 weeks and ip. administration of RGAP (300 mg/kg) for 1 week resulted in antitumor activities of $40\%$ and $45\%$, respectively, indicating that the effect of i.p. injection is more potent 2 and 5 times than that of p.o. one in terms of dose and duration, respectively. Tumor inhibition rates of RGAP at doses of 300, 500, 1000 mg/kg in mice transplanted with B16-F10 melanoma were 4.4, 12.0, and $45.4\%$, respectively, meaning that p.o. dose higher than 500 mg/kg possess marked antitumor activity. The results above suggests that p.o. administration of RGAP also show antitumor activity in vivo depending on the dose.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.266-276
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• 2002

A red ginseng acidic polysaccharide(RGAP) with immunomodulating antitumor activities was isolated from Korean red ginseng, The molecular weight of RGAP was estimated to be 12-450 kDa by gel filtration chromatography, RGAP was found to increase survival rate and to inhibit of tumor growth significantly in a dose dependent manner in mice transplanted with tumor cells. RGAP significantly promoted nitric oxide(NO) production from peritoneal macrophages bothin vivo and in vitro. Western blot analysis exhibited a newly synthesized inducible nitric oxide synthase(iNOS) protein band in the RGAP treated group. It seems likely that immunomodulating antitumor activities of RGAP are mainly mediated by NO production of macrophage. RGAP was further purified by ultrafiltration and anion exchange chromatography on DEAE-sepharose, followed by gel filtration on Sephacryl S-300 to give an active fraction(GFP) with stronger NO production in murine macrophages. GFP increased survival rate ten times compared to RGAP in male ICR mice transplanted with sarcoma 180 and also showed more potent tumoricidal activities of natural killer cells than RGAP. Sugar $composition(mol\%)$ of GFP was found to be arabinose:rhamnose:xylose:galacturonic acid:mannose:galactose:glucose(10:9:1:25:8:20:27) by GC/MS. The results suggest that clinical trials of RGAP in immunotherapy against cancer are highly feasible.

• Journal of Ginseng Research
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• v.27 no.2
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• pp.47-51
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• 2003

Synergistic anticancer activities of red ginseng acidic polysaccharide (RGAS) showing immunomodulatory activity were evaluated by combined treatment with anticancer agents such as Cyclophosphamide (CY) or 5-Fluorouracil (5-FU) in experimental tumor models. The combined treatment of RGAP (100 mg/kg) and CY (3 mg/kg) exhibited 71% of survival rate in lift span of sarcoma 180-bearing mice, while single treatment of RGAP (100 mg/kg) and CY (3 or 10 mg/kg) exhibited 43, 14 and 43% of survival rates, respectively. In addition, when RGAP (100 mg/kg) was administered in combination with 5-FU (2.5 mg/kg) to sarcoma 180 tumor-bearing mice, higher survival rate was found when compared with RGAP or 5-FU treatment alone. Moreover, tumor weights in LL/2 lung carcinoma-bearing mice treated combined with RGAP (100 mg/kg) and 5-FU (5 or 10 mg/kg) was obviously decreased when compared with 5-FU alone. These results suggest that clinical trials of RGAP as an adjuvant in cancer chemotheraphy can be higly feasible.