• Journal of Ginseng Research
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• v.35 no.4
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• pp.462-470
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• 2011

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-${\gamma}$, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.25-33
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• 2004

In this study we investigated whether ATP loss was involved in the potentiated death of immunostimulated rat primary astrocytes in glucose-deprived condition. Rat primary astrocytes immunostimulated with LPS plus IFN-${\gamma}$ for 48 h underwent death upon glucose deprivation, which dependent on the production of peroxynitrite. Intracellular ATP level synergistically decreased by glucose deprivation in immunostimulated astrocytes but not in control cells, and the loss of ATP occurred well ahead of the LDH release. The synergistic cell death and ATP loss by immunostimulation and glucose deprivation were inhibited by iNOS inhibitor (L-NAME and L-NNA) or peroxynitrite decomposition catalyst (also a superoxide anion scavenger), Mn(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (MnTMPyP). Exogenous addition of peroxynitrite generator, SIN-l timedependently induced ATP loss and cell death in the glucose-deprived astrocytes. Depletion of intracellular glutathione (GSH) and dis겨ption of mitochondrial transmembrane potential (MTP) were also observed under same conditions. Supply cellular ATP by the addition of exogenous adenosine or ATP during glucose deprivation inhibited ATP depletion, GSH depletion, MTP disruption and cell death in SIN-l treated or immunostimulated astrocytes. This study showed that perturbation in the regulation of intracellular ATP level in immunostimulated astrocytes might make them more vulnerable to energy challenging stimuli.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.8
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• pp.1098-1104
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• 2005

The trial was carried out on twenty-one Friesian cows at the end of eight months gestation, nine multiparous and twelve primiparous; allocated into three groups (1 control, 2 and 3 experimental). The same diet was administred to all three groups before partum (12.8 kg DM/head/day) and after partum (18.8 kg DM/head/day). The cows in groups 2 and 3 received two different daily quantities of amino-acid chelated chromium (0.6 and 1.2 mg Cr/kg DM) from 4 weeks prior to presumed parturition to 6 weeks after. The milk yield control was carried out at 15, 30, 42 and 60 days. All animals were immunised two weeks prior to the presumed parturition and two weeks after with the following antigens: ovalbumin and brucellergene. Blood samples were collected weekly to monitor humoral and cell-mediated immune responses. When analysing the results of antibody immunity (ovalbumin) in the sixth blood collection both treated groups significantly increased compared to group 1 (0.5230 and 0.4536 vs. 0.1812 OD; p<0.05). The results of the cell-mediated immune response (brucellergene) had significant differences (p<0.10) in correspondence to the third (between group 2 and control) and the fifth (between groups 3 and 2) blood collection. Significant differences in fat corrected milk were observed at 42 days between group 3 and the other two groups (31.01 vs. 26.99 and 28.66 kg/d, p<0.05) and at 60 days between group 3 and control (30.88 vs. 26.69 kg/d, p<0.05). Before partum and at partum a positive immune response was obtained with a lower dose of chromium. After partum a positive immune response, anti-OVA indicator, was obtained with the higher dose of chromium while, $\gamma$-IFN indicator, with the lower dose. A significant increase of the milk yield resulted at both 42 and 60 days with the highest level of chromium.

• Journal of Microbiology and Biotechnology
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• v.17 no.9
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• pp.1513-1520
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• 2007

[ ${\beta}$ ]-1,3-Glucans enhance immune reactions such as antitumor, antibacterial, antiviral, anticoagulatory, and wound healing activities. ${\beta}$-1,3-Glucans have various functions depending on the molecular weight, degree of branching, conformation, water solubility, and intermolecular association. The molecular weight of the soluble glucan was about 15,000 as determined by a high-performance size exclusion chromatography. From the infrared (IR) and $^{13}C$ NMR analytical data, the purified soluble glucan was found to exclusively consist of ${\beta}$-D-glucopyranose with 1,3 linkage. We tested the immunestimulating activities of the soluble ${\beta}$-1,3-glucan extracted from Agrobacterium sp. R259 KCTC 1019 and confirmed the following activities. IFN-$_{\gamma}$ and each cytokines were induced in the spleens and thymus of mice treated with soluble ${\beta}$-1,3-glucan. Adjuvant effect was observed on antibody production. Nitric oxide was synthesized in monocytic cell lines treated with ${\beta}$-1,3-glucan. The cytotoxic and antitumor effects were observed on various cancer cell lines and ICR mice. These results strongly suggested that this soluble ${\beta}$-1,3-glucan could be a good candidate for an immune-modulating agent.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.66-71
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• 2013

Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of inflammatory disorders in Chinese medicine, especially respiratory inflammation. Previously, a new phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-inflammatory activity against several animal models of inflammation, especially against an animal model of acute bronchitis. In the present investigation, the effects of BL on animal models of septic inflammation and chronic bronchitis are examined. Against lipopolysaccharide (LPS)-induced septic inflammation in mice, BL (200-400 mg/kg) reduced the induction of some important proinflammatory cytokines. At 1 h after LPS treatment, BL was found to considerably inhibit TNF-${\alpha}$ production when measured by cytokine array. At 3 h after LPS treatment, BL inhibited the induction of several proinflammatory cytokines, including IFN-${\gamma}$ and IL-$1{\beta}$, although dexamethasone, which was used as a reference, showed a higher inhibitory action on these biomarkers. Against chronic bronchitis induced by LPS/elastase instillation in rats for 4 weeks, BL (200-400 mg/kg/day) significantly inhibited cell recruitment in bronchoalveolar lavage fluid. Furthermore, BL considerably reduced lung injury, as revealed by histological observation. Taken together, these results indicate that BL may have a potential to treat systemic septic inflammation as well as chronic bronchitis.

• The Korean Journal of Food And Nutrition
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• v.23 no.2
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• pp.141-146
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• 2010

Cisplatin(cis-diamminedichloroplatium) is one of the most effective anti-cancer drugs being clinically used in the treatment of solid tumors. Despite its therapeutic benefits, its use in clinical practice is often limited because of dose related toxicity. It is known that yeast cell wall beta-glucans possess immuno-modulating properties, which allows for their application in antitumor therapy. IS2 is a kind of beta-glucan derived from the cell wall of mutated Saccharomyces cerevisiae, which exhibits anti-cancer activity in vitro and in vivo. The present study explored the possibility of combination therapy of IS2 with cisplatin. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of IS-2 in combination with cisplatin effectively inhibited tumor metastasis compared with cisplatin alone or IS-2 treatment in vivo. IS-2 effectively enhanced Th1 type cytokines including IFN-$\gamma$, IL-2, IL-12 and GM-CSF. Simultaneously, this combined treatment inhibited production of Th2 type cytokines compared with control. These results suggested that IS-2 can be applied in combination therapy with anti-cancer drugs to minimize their side effects.

• The Korea Journal of Herbology
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• v.23 no.1
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• pp.53-61
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• 2008

Objectives : The aim of this study was to investigative the effects of Gagambojungikgi-tang (GBT), a Korean herbal medicine, on the immune mediators, T cell proliferation and wound healing in the recombinant Sj26 (rSj26) antigen induced atopic dermatitis(AD) model mice. Methods : GBT is the water extracts prepared from mixture of Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Atractylodes Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Artemisia iwayomogi Herba, Scutellaria Radix, Lonicera japonica Flos. This is a modified prescription of Bojungikgi-tang, which has been used for the treatment of indigestion, and immunological disease in east-asian countries. GBT was orally administered or externally applied at difference doses. The levels of immune mediators [(IgE, IgG1, prostaglandin E2 (PGE2), Th1/Th2 cytokines], T cell proliferation, and wound healing in the rSj26 or chemical antigen induced AD model BALB/c were investigated. Results : GBT dose-dependently suppressed the release of TNF-${\alpha}$, IL-$1{\beta}$ (Th1 cytokines), IL-4, IL-10 (Th2 cytokines), PGE2 (inflammatory mediators) and T cell proliferation. But GBT increased the production of IFN-${\gamma}$ (Th1 cytokine). Furthermore, A wound healing effect of GBT was similar to external application of dexamethasone. Conclusions : These results suggest that GBT suppresses the inflammatory mediators and regulates the Thl/Th2 cytokines, and promotes the wound healing. Therefore, these properties may contribute to the strong anti-AD effect of GBT.

• YAKHAK HOEJI
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• v.47 no.3
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• pp.167-175
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• 2003

Eleutherococcus senticosus is a typical oriental folk medicinal herb. It has been used clinically as a anti-rheumatic disease, anti-stress, ischemic heart disease and gastric ulcer. In the present study, we examined the adjuvant activity of the crude polysaccharides fraction from Eleutherococcus senticosus, EN-3, on the induction of humoral and cellular immune responses against bovine serum albumin (BSA) or ovalbumin (OVA). The thioglycollate-induced macrophages and silica-induced dendritic-like cells cultured with BSA and EN-3 synergistically increased the production of TNF-$\alpha$ and IL-12. When mice were subcutaneously immunized with BSA + EN-3, the antibody titer against BSA was showed significantly higher than those immunized with BSA alone. In addition, when mice were immunized with OVA + FIA + EN-3, the antibody titer was showed similar patterns with the FCA. The assay for determining subisotype of antibody revealed that EN-3 augmented OVA-specific antibody titer of IgG1 and IgG2b. The culture supernatant obtained from splenocytes of mice treated with OVA + FIA + EN-3 also showed a higher level of both OVA-specific Th1-type (IL-2, IFN-${\gamma}$ and GM-CSF) and Th2-type cytokine (IL-4, IL-6 and IL-10). In vitro analysis of T cell proliferation to OVA on 8 weeks, the splenocytes of mice treated with OVA + EN-3 showed a significantly higher proliferating activity than those treated with OVA alone. These results suggest that EN-3 may possess adjuvant activities to potentially to enhance humoral as well as cellular immune response.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.10
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• pp.1329-1335
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• 2006

LP-BM5 murine leukemia retrovirus induces the excessive oxidative stress and immune dysfunction leading to B cell leukemia and murine AIDS with cytokine dysfunction. In the present study, the immune restoratory effect of antioxidant hormone dedydroepiandrosterone sulfate (DHEAS) was investigated in the primary splenocytes from LP-BM5 retrovirus-infected C57BL/6 mice. DHEAS significantly increased T and B cell response to mitogen and normalized the unbalanced production of Th1/Th2 type cytokines. In particular, both protein and mRNA expression of IL-4, IL-6, and $TNF-\alpha$ were down-regulated by DHEAS treatment whereas IL-2 and $IFN-\gamma$ level were increased. This result suggests that DHEAS directly or indirectly regulates the gene expression of Th1/Th2 type cytokines in transcription level. In addition, DHEAS treatment decreased the hepatic lipid peroxidation and preserved vitamin E level in liver cells. These results suggested that DHEAS could effectively prevent immune dysfunction by regulating cytokine secretion and preventing the oxidative stress in murine AIDS.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.131-145
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• 2007

To evaluate the effects of GP on contact dermatitis, we examined the composition of immune cells from drain lymph node in DNCB-induced contact dermatitis murine model NC/Nga mice. And the amount of pathologic cytokines of spleen and antioxidant activity were investigated. The results were summarized as followers; 1. GP did not show cytotoxic effect on mLFC in vitro. 2. GP did not have hepatotoxicity in vivo in the level of ALT, AST. 3. GP decreased the production of DPPH and in a dose-dependent. 4. GP significantly decreased total cell number of DLN in DNCB-induced NC/Nga mice compared to the untreated control group. 5. GP significantly decreased the number of CD3+, CD19+, CD4+, CD8+, CD3+/CD69+ and CD4+/CD45+ in DLN of DNCB-induced NC/Nga mice compared to the untreated control group. 6. GP significantly reduced the level of IL-4 and IFN-$\gamma$ in splenocytes of DNCB-induced NC/Nga mice compared to the untreated control group. Taken together above results, GP have therapeutic effects on contact dermatitis by regulating T cell activation. This study warranted further investigations of molecular mechanisms of GP on contact dermatitis.