• YAKHAK HOEJI
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• v.51 no.4
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• pp.270-276
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• 2007

Silybin is known to be a major active flavonoid component isolated from Silybum marianum, a hepatoprotective medicinal plant. In this study, we examined the immunomodulatory role of silybin on T cell and macrophage-mediated immune responses. To do this, the proliferation of splenic lymphocytes and CD8+ CTLL-2 cells under mitogenic stimulation with lipopolysaccharide (LPS), concanavalin (Con) A and interleukin (IL)-2 and the production of $TNF-{\alpha}$ and NO from LPS- and $IFN-{\gamma}$-activated macrophages was evaluated under silybin treatment. The mitogenic proliferation of splenic lymphocytes induced by LPS and Con A was strongly diminished by silybin in a dose-dependent manner. Moreover, the proliferation of CD8+ CTLL-2 cells was also negatively modulated by the compound. In contrast, silybin did not strongly suppress the proliferation of normal splenocytes and T cell line Sup-T1 cells, indicating that the inhibitory effect of silybin may be due to blocking only mitogenic responses of splenic lymphocytes. In addition, silybin inhibited $TNF-{\alpha}$ production in LPS-stimulated RAW264.7 cells. Effect of silybin however was distinct, according to NO-inducing stimuli. Thus, silybin only blocked NO production induced by $IFN-{\gamma}$ but not LPS and the inhibition was increased when PMA was co-treated with $IFN-{\gamma}$. Unlike NO inhibition, however, this compound protected the cytotoxic damage of RAW264.7 cells induced by both LPS and $IFN-{\gamma}$. Therefore, our data suggest that silybin may participate in host immune responses mediated by T cells and macrophages via regulating mitogenic proliferation, and the production of $TNF-{\alpha}$ and NO, depending on cellular stimuli.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1140-1146
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• 2004

This study was carried out to investigate the comparison of immunomodualtory effects of water-extracted Ginseng Radix(GR), Pilose Asia-bell(PA), Astragali Radix(AR), Astractylodes Rhizoma alba(AA) and Dioscoreae Rhizoma (DR). The parameter examined to assess apparent immunomodulatory effect of the water-extracted GR, PA, AR, AA and DR included the regulation of Nitric oxide (NO), the expression of Th1/Th2 type cytokine, the change of B cell phenotype. The water-extracted GR, PA, AR, AA and DR inhibited NO production and iNOS protein expression in LPS stimulated RAW 264.7 macrophage cells. In the Th1 and Th2 cytokine expression, the water-extracted GR, PA, AR, AA and DR induced IL-2 and IFNr mRNA gene expression. Therefore, it seems that the water-extracted GR, PA, AR, AA and DR have a inducing effect of Th1 type cytokines. In the Flow cytometry analysis, the water-extracted GR, PA, AR, AA and DR did not change B cell phenotype (CD45R/B220). The water-extracted GR, PA, AR, AA and DR have a reducing effect of immune suppression cause by Methotrexate (MTX), an agent of immune suppression. These results suggest that the immunomodulatory effects of the water-extracted GR, PA, AR, AA and DR may be, in part, associated with the inducing IL-2 and IFNr mRNA gene expression in and regulation of NO production in macrophage cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1000-1010
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• 2005

This study was carried out to investigate the comparison of immunomodualtory effects of water-extracted Aconiti lateralis Preparata Radix(PR), Zingiberis Rhizoma(ZR), Cinnamomi Cortex(CC) and Evodiae Fructus(EF). The parameter examined to assess apparent immunomodulatory effect of the water-extracted PR, ZR, CC and EF included the regulation of Nitric oxide (NO). Also, ZR and EF represent the expression of Th1/Th2 type cytokine, the change of B cell phenotype. The water-extracted PR, ZR, CC and EF inhibited NO production and iNOS protein expression in LPS stimulated RAW 264.7 macrophage cells. In the Th1 and Th2 cytokine expression, the water-extracted ZR and EF induced IL-2, IFNr and IL-10 mRNA gene expression. Therefore, it seems that the water-extracted ZR and EF have a inducing effect of Th1 and Th2 type cytokines. In the Flow cytometry analysis, the water-extracted ZR and EF changed B cell phenotype (CD45R/B220), did NOT in PR and CC. The water-extracted PR, ZR, CC and EF have a reducing effect of immune suppression cause by Methotrexate (MTX), an agent of immune suppression. These results suggest that the immunomodulatory effects of the water-extracted ZR and EF may be, in part, associated with the inducing IL-2 and IFNr mRNA gene expression In and regulation of NO production in macrophage cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.48-55
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• 2019

Current studies have been reported that fruits such as berries may contain both antioxidant and antitumor polyphenols that may be important in this regard. We investigated the immunostimulatory effect of fermented blueberry (Vaccinium corymbosum L.) on cyclophosphamide-induced immunosuppression in animal model. Rats were administered blueberry yeast fermented powder (BYFP) at doses 30, 100, and 300 mg/kg for 4 weeks after cyclophosphamide (Cy) treatment, respectively. The immunomodulatory effect of BYFP were measured both in vitro and in vivo, and the changes of blood components were also analyzed. We found that BYFP recovered immunosuppression-mediated decreased liver, spleen, and thymus weights as well as up regulation of white blood cell, lymphocyte, and neutrophil in blood. Moreover, BYFP up-regulated IL-2, TNF-${\alpha}$, and IFN-${\gamma}$ pro-inflammatory cytokine production compared to immune suppressed control group, respectively. According to histological studies, BYFP regenerated significantly on Cy-mediated injured spleen at the high doses (BYFP 300) comparison with Cy-treated groups (immunosuppression). Collectively, these findings suggest that BYFP may have the potential as a dietary immunostimulatory agent.

• Preventive Nutrition and Food Science
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• v.14 no.2
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• pp.102-108
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• 2009

The comparative immunomodulatory effects of ${\beta}$-glucans isolated from mushroom fungi (Coriolus versicol), yeast (Saccharomyces cerevisiae) and bacteria (Agrobacterium) on the major functions of macrophages were evaluated. As parameters of macrophage functions, we examined tumoricidal activity, phagocytosis, nitric oxide (NO) production, and the induction of inducible NO synthetase (iNOS) in RAW264.7 cells, following treatments with ${\beta}$-glucans from the three different sources. The results indicated that all ${\beta}$-glucan treatments significantly induced tumoricidal activity in the RAW264.7 cells, with a remarkable effect shown by the beta-glucan from Agrobacterium at a concentration of $10{\mu}g/mL$. There was also a significant increase in iNOS-NO system activity in macrophages treated with ${\beta}$-glucans extracted from yeast; however, iNOS-NO system activity was not markedly changed by the treatment of ${\beta}$-glucans from C. versicolor mushroom fungi or Agrobacterium. Furthermore, the ${\beta}$-glucans from C. versicolor had a significant phagocytotic effect at concentrations of 1, 10, and $100{\mu}g/mL$. Taken together, the present data suggest that these ${\beta}$-glucans, isolated from three different sources, have different effects on macrophage function, and therefore, may have different clinical uses in different for various types of diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1443-1448
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• 2004

The present study was conducted to evaluate the immunomodulatory effects of Dangguijakyak-san(당귀작약산). We investigated the effects of cell proliferation in mouse spleen cell and RAW 264.7 macrophages cells. Dangguijakyak-san enhanced mitogenic activity in the dose-response manner in mouse spleen cells and RAW 264.7 macrophages cells. In nitric oxide (NO) synthesis and iNOS mRNA expression by Dangguijakyak-san, Dangguijakyaksan alone had an effect on NO synthesis and iNOS mRNA expression in RAW 264.7 cells. NO production and iNOS mRNA expression which is excessively induced by LPS decreased after treatment of Dangguijakyak-san. The expressions of cytokine gene by Dangguijakyak-san investigated using reverse transcription polymerase chain reaction (RT-PCR). In RT-PCR, IL-1α, IL-1β and IL-6 mRNA expressions induced in Dangguijakyak-san-treated RAW 264.7 cells. These data indicate that 1) Dangguijakyak-san can modulate various immune response and 2) the immunomodulatory effects of Dangguijakyak-san may be, in part, associated with the regulation of NO synthesis, the expressions of these cytokine as well as the mitogenic effect on spleen cells and macrophages cells.

• Preventive Nutrition and Food Science
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• v.11 no.1
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• pp.54-60
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• 2006

The immunomodulatory effect of a new herbal preparation, HemoHIM, on the recovery from leukopenia induced by cyclophosphamide treatment was investigated. The HemoHIM was made up with an addition of the ethanol-insoluble fraction to the total water extract of Angelica Radix, Cnidii Rhizoma and Paeonia Radix. Daily oral administration of 100 mg/kg BW or 500 mg/kg BW HemoHIM accelerated the recovery from cyclophosphamide-induced leukopenia. HemoHIM increased the number of leukocytes and lymphocytes in the peripheral blood when compared with the cyclophosphamide-treated control. Moreover, the suppressed natural killer (NK) cell activity and interferon $(IFN)-{\gamma}$ secretion in the cyclophosphamide-treated mice were restored by the administration of HemoHIM. HemoHIM significantly reduced the abnormally heightened ratio of interleukin $(IL)-4/IFN-{\gamma}$ and immunoglobulin (Ig)E/IgG2a in the cyclophosphamide-treated mice. These results suggest that HemoHIM accelerates the recovery from leukopenia and alleviates the imbalanced T helper (Th)l/Th2 responses in the cyclophosphamide-treated mice. Additionally, HemoHIM was found to stimulate normal splenocytes to secrete not only Thl type cytokines such as $IFN-{\gamma}$ and IL-2, but also Th2 type cytokine IL-4. In conclusion, our results show that HemoHIM certainly has an influence on the balanced recovery of immune cells and the activation of their activities in the cyclophosphamide-treated mice.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.6 no.1
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• pp.29-45
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• 2000

In order to investigate the antitumor effect by Dangguihwalhyultang after B-l6 cells were transplanted in C57BL/6 mice, and the immune responses in mice induced by methotrexate, the extract of Dangguihwalhyultang was orally administered to the ICR mice. Experimental studies were performed for measurance of metastasis, cell cytotoxicity in vitro, life extention, weight of cancer, natural killer cell activity. productivity of interleukin-2. The results were summarized as follows: 1. Mean survival time in Dangguihwalhyultang-treated group was prolonged, as compared with control group(14.63%) significantly(P<0.05). 2. Inhibition of metastasis in Dangguihwalhyultang-treated group was higher than control group with significance on 14th day(P<0.05). 3. On the weight of solid tumor. Dangguihwalhyultang-treated group was less than control group with significance(P<0.05). 4. On the MTT assay. Dangguihwalhyultang concentration inhibited cell viability was $368.8{\mu}g/well$. 5. Natural killer cell activity in Dangguihwalhyultang-treated group was significantly increased on 100:1, 50:1 E/T(effect cell/target cell) ratio(P<0.05). 6. Production of interleukin-2 in Dangguihwalhyultang-treated group was significantly increased(P<0.05).

• YAKHAK HOEJI
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• v.51 no.1
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• pp.35-43
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• 2007

To investigate the immunomodulatory roles of cyclic AMP (CAMP) on macrophage- and T lymphocyte-mediated immune responses, CAMP elevating agents were employed and carefully re-examined under the activation conditions of the cells. Various inhibitors tested dose-dependently blocked tumor necrosis factor (TNF)-${\alpha}$ production with IC$_{50}$ values ranged from 0.04 to 300 ${\mu}$M. Of the inhibitors, cAMP-elevating agents showed lower cytotoxicity assessed by lactate dehydrogenase (LDH) release, suggesting less toxic and more selective. In particular co-treatment of dbcAMP with a protein kinase C inhibitor staurosporine displayed the synergistic inhibition of TNF-${\alpha}$ production. The modulatory effect of dbcAMP on TNF-${\alpha}$ and nitric oxide (NO) was significantly affected by treatment time of dbcAMP. Thus, post-treatment of dbcAMP (three hours before LPS) abrogated dbcAMP's inhibitory activity and rather enhanced TNF-${\alpha}$ level up to 60%. In contrast, additional NO production was shown at the co-treatment of dbcAMP with LPS. Unlike simultaneous treatment of phorbol 12-myristate 13-acetate (PMA) and interferon (IFN)-${\gamma}$co-treatment, the combination of dbcAMP with other NO-inducing stimuli did not show drastic overproduction of NO. cAMP elevating agents also diminished splenocyte proliferation stimulated by concanavalin (Con) A, phytohemaglutinin A (PHA) and lipopolysaccharide (LPS). In addition, dbcAMP but not rolipram strongly suppressed CD8$^+$ T cells (CTLL-2). Finally, cAMP elevating agents were differentially involved in regulating CD98-mediated cell-cell adhesion. Thus, dbcAMP and rolipram significantly enhanced the cell-cell adhesion, whereas forskolin blocked. Therefore, our results suggest that CAMP elevating agents participate in various immune responses mediated by macrophages and T cells with a different fashion depending on cellular environments and activation signals.

• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1395-1403
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• 2020

There is an increasing interest in using inactivated probiotics to modulate the host immune system and protect against pathogens. As the immunomodulatory function of heat-killed Lactobacillus brevis KCTC 12777BP (LBB) and its mechanism is unclear, we investigated the effect of LBB on immune response based on the hypothesis that LBB might exert stimulatory effects on immunity. In the current study, we demonstrate that administration of LBB can exert immune-stimulatory effects and promote clearance of foreign matters through enhancing phagocytosis. Treatment with LBB induced the production of TNF-α, IL-6, and nitric oxide in macrophages. Importantly, LBB directly increased the phagocytic activity of macrophages against bacterial particles. LBB was able to promote the production of TNF-α in bone marrow-derived macrophages and splenocytes and also increase the proliferation rate of splenocytes, suggesting that the immune-stimulating activity of LBB can be observed in primary immune cells. Investigation into the molecular mechanism responsible revealed that LBB upregulates TAK1 activity and its downstream ERK, p38, and JNK signaling pathways. To further confirm the immunomodulatory capability of LBB in vivo, we orally administered LBB to mice and assessed the effect on primary splenocytes. Splenocytes isolated from LBB-treated mice exhibited higher TNF-α expression and proliferative capacity. These results show that heat-killed L. brevis, a wildly consumed probiotic, may provide protection against pathogens through enhancing host immunity.