• Journal of Life Science
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• v.31 no.8
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• pp.745-754
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• 2021

Deterioration of the immune function weakens the body's resistance to various infections, leading to a series of diseases. Immunomodulatory biomaterials have been used to reduce the side effects of immunosuppressants or to enhance immunity. Agarwood is the aromatic resinous portion of Aquilaria trees that has been traditionally used as a medicinal herb for the treatment of various diseases. Although previous studies have shown that agarwood can improve the body's immunity, evidence for this claim is still lacking. In this study, the immune-enhancing effects of the agarwood methanol extracts of Aquilaria malaccensis Lamk were evaluated in a RAW 264.7 macrophage model. Based on the results, the agarwood extracts markedly enhanced phagocytosis in the absence of cytotoxicity. The agarwood extract-treated RAW 264.7 cells exhibited the typical morphology of activated macrophages, which are spindle-shaped with elongated filopodia. Agarwood extract also significantly increased the production of nitric oxide (NO), which is associated with the increased expression of inducible NO synthase. Moreover, the secretion and expression levels of cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β and IL-6, were increased by agarwood treatment. Notably, these are also associated with a mitogen-activated protein kinase signaling pathway. Taken together, our findings provide scientific evidence that agarwood has potential immune-enhancing effects in vitro.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.170-178
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• 2001

Background: Korean mistletoe (Viscum album) extract has been found to posses immunostimulatory activity. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to know whether this extract might activate mouse peritoneal macrophages to produce interleukin $1{\beta}$ (IL-$1{\beta}$). Methods: Hemagglutination assay was carried out to examine whether M11C contained a lectin or not. To know the effect of M11C on the production of IL-$1{\beta}$, the macrophages were treated by the M11C, and then collected the supernatant (M11C stimulated macrophages-conditioned media; MMCM). MMCM was analyzed for the IL-$1{\beta}$ quantification and mRNA expression by means of ELISA and RT-PCR, respectively. Results: Maximum effective dose and time of M11C on IL-$1{\beta}$ production from macrophages were $20{\mu}g/m{\ell}$ and 8 hours, respectively. This ELISA data was reconfirmed by immunoblotting assay. indicating that M11C is a good candidate for an immunomodulator. The dose and time dependent effects of M11C on the expression of IL-$1{\beta}$ mRNA from macrophages was also shown in expression of mRNA detected by RT-PCR. Treatment dose and time for the maximum expression of IL-$1{\beta}$ mRNA were $20{\mu}g/m{\ell}$ and 4 hours, respectively. Maximum gene expression of IL-$1{\beta}$ was much earlier than maximum production of it. Conclusion: As results, Korean mistletoe extract, M11C, may be used for an immunomodulator. This will be able to make up for and solve the problems caused by existent immunoagent with many adverse effects through many other studies in future including one molecule extraction.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.2
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• pp.46-58
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• 2014

Objectives: This study was designed to investigate intestinal immune system activation and anti-metastatic effect on cancer cells by orally administered extracts of Boyanghwano-tang. Methods: To observe immunomodulating effects of Boyanghwano-tang on Peyer's patch cells, we measured cytokines GM-CSF, IL-4. In addition to observing effects of Boyanghwano-tang on hematopoiesis, we measured proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. IgA induction activated in intestinal content and serum was measured to observe the effect of orally administered Boyanghwano-tang on mucosal immune system. After administering ovalbumin (OVA) with Boyanghwano-tang, Proliferation of Peyer's patch cell was measured to investigate gut immunostimulatory effect. Anti-metastatic experiments were conducted in vivo mouse model by using colon 26-M3.1 carcinoma cell. Results: The amounts of GM-CSF and IL-4 in the culture supernatant of Peyer's patch cells were significantly increased compared to the control group. The proliferation of bone marrow cell was significantly up-regualted with Boyanghwano-tang. These results indicate that oral administration of Boyanghwano-tang enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-4 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation. After orally administering OVA with Boyanghwano-tang, IgA induction and Proliferation of peyer's patch cell was up-regulated with Boyanghwano-tang. These results means orally administered Boyanghwano-tang activates intestinal immune system and has an inhibitory effect on tumor metastasis. In addition, We found that orally administered Boyanghwano-tang significantly inhibited tumor metastasis in vivo. Conclusions: Orally administered Boyanghwano-tang appears to have considerable activity on the anti-metastasis by activation of immune system.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.2
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• pp.34-45
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• 2014

Objectives: This study was designed to investigate intestinal immune system activation and antimetastatic effect of Ojeok-san on cancer cells by oral administration. Methods: Cell viability of Ojeok-san was tested with colon 26-M3.1 carcinoma cells and Peyer's patch cells in vitro. Antimetastatic experiments were conducted in vivo mouse model by using colon 26-M3.1 carcinoma cell. To observe immunomodulating effects of Ojeok-san on Peyer's patch cells, we measured interleukin (IL)-4, GM-CSF. In addition to observing effects of Ojeok-san on hematopoiesis, we measured proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. IgA induction activated in serum and intestinal content was measured to observe the effect of orally administered Ojeok-san on mucosal immune system. After administering Ovalbumin (OVA) with Ojeok-san, Proliferation of Peyer's patch cell was measured to investigate gut immunostimulatory effect. Results: in vitro cytotoxicity analysis, the inhibitory concentration $(IC)_{50}$ of the colon 26-M3.1 carcinoma cell was $890{\mu}g/ml$. $IC_{50}$ of the Peyer's patch cells with LPS was $990{\mu}g/ml$. We found that orally administered Ojeok-san significantly inhibited tumor metastasis in vivo. In addition, the amounts of IL-4 and GM-CSF in the culture supernatant of Peyer's patch cells were significantly increased compared to the control group. The proliferation of bone marrow cell was significantly up-regulated with Ojeok-san. These results indicate that oral administration of Ojeok-san enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-4 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation. After orally administering Ovalbumin (OVA) with Ojeok-san, IgA induction and Proliferation of peyer's patch cell was up-regulated with Ojeok-san. These results means orally administered Ojeok-san activates intestinal immune system and has an inhibitory effect on tumor metastasis. Conclusions: Orally administered Ojeok-san appears to have considerable activity on the anti-metastasis by activation of immune system.

• Journal of Life Science
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• v.27 no.4
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• pp.482-499
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• 2017

Allergic diseases have increased over the past several decade worldwide including developing countries. Allergic inflammatory responses are caused by Th (T helper)2 immune responses, triggered by allergen ingestion by antigen presenting cells such as dendritic cells (DCs). Intestinal microorganisms control the metabolism and physiological functions of the host, contribute to early immune system maturation during the early life, and homeostasis and epithelial integrity during life. Bifidobacteria have strain-specific immunostimulatory properties in the Th1/Th2 balance, inhibit TSLP (thymic stromal lymphopoietin) and IgE expression, and promote Flg (Filaggrin) and FoxP3 (Treg) expression to alleviate allergies. In addition, unmethylated CpG motif ODN (oligodeoxynucleotides) is recognized by TLR (toll-like receptors)9 of B cells and plasmacytoid dendritic cells (pDCs) to induce innate and adaptive immune responses, while the butyrate produced by Clostridium butyricum activates the GPR (G-protein coupled receptors)109a signaling pathway to induce the expression of anti-inflammatory gene of pDCs, and directly stimulates the proliferation of thymically derived regulatory T (tTreg) cells through the activation of GPR43 or inhibits the activity of HADC (histone deacetylase) to differentiate naive $CD4^+$ T cells into pTreg cells through the histone H3 acetylation of Foxp3 gene intronic enhancer.

• Korean Journal of Pharmacognosy
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• v.34 no.3 s.134
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• pp.210-217
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• 2003

Korean mistletoe (Viscum album) extract has been found to posses immunostimulatory activity. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to know whether this extract might activate mouse splenic macrophages to produce tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}$) and might play a role in anticancer. To know the effect of M11C on the production of $TNF-{\alpha}$, the splenic macrophages were treated by the M11C, and then collected the supernatant (M11C stimulated splenic macrophage-conditioned media; MSCM). MSCM was analyzed for the $TNF-{\alpha}$ secretion by means of ELISA and immunoblotting, and mRNA expression was analyzed by RT-PCR. The S-180 murine sarcoma model was established to know the effect of M11C on the inhibition of tumor growth. M11C had the effect of $TNF-{\alpha}$ production from splenic macrophages performed by ELISA technique. This ELISA data was reconfirmed by immunoblotting assay. The effects of M11C on the expression of $TNF-{\alpha}$ mRNA from the macrophages was also shown. M11C also had the inhibitory effect of S-180 tumor growth. These data suggest that Korean mistletoe extract M11C may be used for an immunomodulator.

• Korean Journal of Food Science and Technology
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• v.53 no.5
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• pp.570-577
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• 2021

This study elucidated the biological activities and structural characteristics of polysaccharides isolated from ginseng leaves fermented using Cordyceps sinensis (GLF). GLF comprised at least 18 glycosyl linkages, including 4-linked glucose residues (24.0%). To characterize the neutral polysaccharides in GLF, it was further fractionated by anion exchange chromatography, and the unabsorbed fraction (GLF1) was isolated. Peritoneal macrophages stimulated with GLF1 produced various cytokines in a dose-dependent manner. The properties and activities of the four subfractions (PHI, PHIA1-PHIA3) obtained after sequential enzymatic digestion were examined. PHI and PHIA3 primarily comprised glucose, whereas PHI exhibited an iodine-color reaction. Furthermore, the PHIA1-3 fractions indicated that cytokine production was completely inhibited. These results suggest at the immune activities of GLF1 may be due to the α-(1→4)-glucan branched at the C(O)6 position, which was produced by C. sinensis.

• Korean Journal of Food Science and Technology
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• v.31 no.3
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• pp.838-847
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• 1999

Based on the results that the extract of Korean mistletoe (KM-110) has immunological and anti-tumor activities and its main component is lectin called KML-U, this study was carried out to investigate the immunostimulatory and anti-tumor activities of FKM-110, fermented KM-110 with lactobacillus, as a basic study for the development of functional food with anti-tumor activity. The amount of lectin after fermentation determined by ELISA was varied with the fermentation time and kinds of lactobacillus. Cytotoxic effects of FKM-110 on the various tumor cells was significant and dependent on the concentration of KML-U and the kinds of lactobacillus. FKM-110 stimulated macrophage and resulted in the secretion of some cytokines such as IL-1 and $IFN-{\gamma}$, but this effect was not correlated with the concentration of lectin. FKM-110 fermented with Marshall Lactobacillus casei showed the most potent antitumor activity in experimental and spontaneous metastasis models. When yoghurt produced with KM-110, Marshall Lactobacillus casei and skim milk was administered orally to mouse, the metastasis of tumor cells was significantly inhibited.