• Food Science of Animal Resources
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• v.38 no.6
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• pp.1226-1236
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• 2018

Ovotransferrin (OTF) is a well-known protein of the transferrin family with strong iron chelating activity, resulting in its antimicrobial activity. Furthermore, OTF is known to have antioxidant, anticancer, and antihypertensive activities. However, there have been few studies about the immune-enhancing activity of OTF. In current study, we investigated the immune-enhancing activity of OTF using the murine macrophage cells in vitro. The effect of OTF on production of pro-inflammatory mediators and cytokines were determined using Griess assay and quantitative real-time PCR. Using Neutral Red uptake assay, we confirmed the effect of OTF on phagocytic activity of macrophages. Ovotransferrin significantly increased the production of nitric oxide (NO) and secretion of inducible nitric oxide synthase (iNOS) mRNA with no cytotoxic activity. Ovotransferrin (2 mg/mL) stimulated NO production up to $31.9{\pm}3.5{\mu}M$. Ovotransferrin significantly increased the mRNA expression levels of pro-inflammatory cytokines which are tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), Interleukin-$1{\beta}$ (IL-$1{\beta}$), and IL-6: OTF (2 mg/mL) treatment increased the secretion of mRNA for TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by 22.20-, 37.91-, and 6.17-fold of the negative control, respectively. The phagocytic activity of macrophages was also increased by OTF treatment significantly compared with negative control. Also, OTF treatment increased phosphorylation level of MAPK signaling pathways. These results indicated that OTF has immune-enhancing activity by activating RAW 264.7 macrophages via MAPK pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1337-1342
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• 2004

The purpose of this research was to investigate the immunoregulatory effect and the leukemia cell apoptosis of EtOH extract of OGAPI(OGP). The proliferation of cultured splenocytes, thymocytes and mesenteric lymph node cells were enhanced by the addition of OGP. Splenic and thymic T lymphocytes, especially TH and Tc cells were significantly increased in OGP-administered mice. OGP markedly increased the production of γ-interferon in mice serum and accelerated the phagocytic activity in peritoneal macrophages. OGP treatment enhanced the apoptosis of L1210 mouse leukemia and Jurkat, Molt4 human leukemia cells, and increased the expression of apoptosis-related ICE, c-myc, p53 gene in Jurkat cell. These results suggest that OGP have an immunoregulatory action and anti-cancer activity.

• Journal of Nutrition and Health
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• v.31 no.6
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• pp.1076-1081
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• 1998

The purpose of this research was to isolate an active component on immunoytes from 70% MeOH extract of Codonopsis lanceolatae Radix(CLE). CLE was fractionated successively with hexane, methylene chloride, n-butyl alcohol and water, and then the water fraction was separated with molecularporous membrane tubing(m.w. 3,500). Each fraction(50mg/kg) was administered p.o. once a day for 7 days in BALB/c mice respectively. None of these fractions affected the apoptosis and mitochondrial transmembrane potential in thymocyte. Hexane and methylene chloride fractions decreased CD4$^{[-10]}$ CD8$^{+}$ single-positive cells, and the water fraction enhanced CD4$^{+}$ CD8$^{[-10]}$ single-positive cells in thymocyte. The proliferation of thymocytes was decreased by the fraction hexane, but was enhanced by the water fraction. Hexane, methylene chloride and butyl alcohol fractions suppressed the production of nitric oxide, which was not affected by the water fraction. Hexane and butyl alcohol fraction suppressed the phagocytic activity, but water fraction enhanced it. The components(m.w. 3,500 above) separated from the water fraction enhanced the proliferation of thymocyte, the population of CD4$^{+}$ CDB$^{[-10]}$ single-positive cells, and phagocytic activity in macrophage. These results suggest that the stimulative components of proliferation, TH population and phagorytc activity is in the water fraction, and the molecular weight is 3,500 above. (Korean J Nutrition 31(6) : 1076~1081, 1998) 1998)

• The Korean Journal of Food And Nutrition
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• v.9 no.1
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• pp.69-75
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• 1996

In order to research for compound of immunomodulatic and anti-allergic function. These experiments were conducted to investigated the effects of hot water extracts(PRWE) , ethanol extracts (PREE) and polysaccharide fraction extracts (PRPE) extracted from platycodi radix on immune response. The effect of these platycodi radix extracts on hemagglutinin titer(HA), hemalysin titer(HY), plaque forming cell(PFC), rosette forming cell (RFC) and phagocytosis was Investigated by using BALB / C mice. The results obtained from this study are as follows. Generally, the oral administration of extracts fractions for 10 days each other resulted in the enhanced HA and HY. In the experiment of PFC and RFC, the results of experimental groups which was given each samples compared to control group showed the enhanced level of activity such as PRPE 160% and 196% each other But PRWE and PREE decreased or wear not changed. When PREE, PRPE or PRWE was given to mice orally, PREE and PRPE significantly enhanced the phagocytic activity of peritoneal exudate cells(PEC), spleen cells(SC) and monolymphocytus cell(MC), about from 150% to 250%, but PRW was decreased.

• The Korean Journal of Food And Nutrition
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• v.29 no.3
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• pp.341-346
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• 2016

Phagocytosis is a primary and an essential step of host defense, and is triggered by the interaction of particles with specific receptor of macrophages. In this study, we investigated the effect of extracts of Rudbeckia laciniata (RLE) on the phagocytic activity of macrophage, by monitoring the phagocytosis-associated signal transduction. RLE markedly increased phagocytosis of serum-opsonized zymosan particles (SOZ), while phagocytosis of IgG-opsonized zymosan particles (IOZ) or none-opsonized zymosan particles (NOZ) remained unaffected. However, RLE did not affect the binding of opsonized zymosan particles (OZ) with the cell surface of macrophage. This suggests that RLE may regulate SOZ-induced intracellular signaling during phagocytosis of macrophage. To confirm this hypothesis, we investigated whether RLE was involved in the RhoA-mediated signal transduction during phagocytosis of SOZ. Inhibitors of the RhoA-mediated signaling pathway, such as Y-27632 (for ROCK), ML-7 (for MLCK), and Tat-C3 (for RhoA), totally blocked phagocytosis of SOZ enhanced by RLE, as well as phagocytosis of SOZ. Additionally, RhoA activity was markedly increased when cells were treated with RLE, suggesting that RLE could increase the phagocytic activity of macrophage via RhoA-ROCK/MLCK signal pathway. Thus, RLE may be used to develop functional foods for immunity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.2
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• pp.235-240
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• 2000

Inhibitory effects of cockle extracts on carcinogen-induced cytotoxicity in C3H/10T1/2 cells were studied. Soup (62$\mu\textrm{g}$/mL), solubility (28$\mu\textrm{g}$/mL) and liposolubility (9 $\mu\textrm{g}$/mL) of the cockle inhibited 3-methyl-cholanthrene(MCA)-induced cytotoxicity in C3H/10T1/2 cells by 53 and 94%, respectively. These results suggest that the extracts cockle might have anticarcinogen-induced cytotoxicity of C3H/10T1/2 cells. The effects of cockle extracts on the immune response related to its antitumor activity in vitro and in vivo were investigated. The cockle extracts showed a direct cytotoxic effect on sarcoma-180 cells, tumor cells in vitro. Soup (0.49 mg/mL), solubility (0.11 mg/mL) and liposolubiliy (0.05 mg/mL) of the cockle markedly decreased the total numbers of sarcoma-180 cells, but not their viability. The phagocytic acitivity of peritoneal macrophage of mice was significantly augmented by these extracts of the cockle compared with that of control in vivo. These extracts also raised the phagocuytic index, indicating that the number of phagocytize dmicrobes per macrophage increased. Thus, cockle extracts might show a antitumor activity by enhancing the phagocytic cell activities.

• BMB Reports
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• v.52 no.11
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• pp.635-640
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• 2019

CpG-DNA triggers the proliferation and differentiation of B cells which results in the increased production of antibodies. The presence of bacteria-reactive IgM in normal serum was reported; however, the relevance of CpG-DNA with the production of bacteria-reactive IgM has not been investigated. Here, we proved the function of CpG-DNA for the production of bacteria-reactive IgM. CpG-DNA administration led to increased production of bacteria-reactive IgM both in the peritoneal fluid and serum through TLR9 signaling pathway. When we stimulated B cells with CpG-DNA, production of bacteria-reactive IgM was reproduced in vitro. We established a bacteria-reactive monoclonal IgM antibody using CpG-DNA stimulated-peritoneal B cells. The monoclonal IgM antibody enhanced the phagocytic activity of RAW 264.7 cells against S. aureus MW2 infection. Therefore, we suggest that CpG-DNA enhances the antibacterial activity of the immune system by triggering the production of bacteria-reactive IgM. We also suggest the possible application of the antibodies for the treatment of antibiotics-resistant bacterial infections.

• The Korea Journal of Herbology
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• v.29 no.1
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• pp.1-6
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• 2014

Objectives : Many of currently used anti-cancer drugs were developed to target cell death mechanisms and had serious side effects by causing damage to normal cells. Hangambujeongsan or Kangai Fuzheng Powder was a mixture based on the traditional Chinese medicine. It had been used in the local Chinese hospitals to treat cancer patients for decades and had shown a certain level of beneficial effects without major toxic effects. But its mechanism of action had not been elucidated yet. Thus this study aimed to investigate the effects of Kangai Fuzheng Powder in an in vitro experiment. Methods : Cancer lines or RAW264.7 mouse macrophage cells were treated with Kangai Fuzheng Powder. Cell viability was measured by MTT assay, and morphological observation was also performed. Gene expression of cytokines in macrophages was determined by real-time polymerase chain reaction. Phagocytic function assay was also performed in macrophage cells. Results : Kangai Fuzheng Powder had no direct detrimental effect on cancer cells. When macrophages were co-cultured with cancer cells, Kangai Fuzheng Powder had toxic effect on cancer cells. After exposing macrophages to Kangai Fuzheng Powder, macrophages transformed into activated form and the mRNA level of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10 and monocyte chemotactic protein-1 was significantly enhanced. Phagocytic activity of macrophages was dramatically potentiated. Conclusions : We demonstrated that anti-cancer effect of Kangai Fuzheng Powder was related to activation of macrophages including enhanced cytokine production and phagocytic function.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.438-444
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• 2011

The mushroom Coriolus versicolor contains biologically active polysaccharides, most of which belong to the ${\beta}$-glucan group. Diverse physicochemical properties, due to different sources and isolated types of ${\beta}$-glucans, can induce distinct biological activities. We investigated the effects of ${\beta}$-glucans from C. versicolor on phagocytic activity, nitric oxide (NO), TNF-${\alpha}$ production, and signaling of dectin-1, a well-known ${\beta}$-glucan receptor, in macrophages. ${\beta}$-Glucans increased phagocytic activity and TNF-${\alpha}$ and NO-iNOS/eNOS production. Laminarin, a specific inhibitor of dectin-1, showed strong inhibitory effects on phagocytosis and subsequent TNF-${\alpha}$, iNOS, and eNOS production increased by ${\beta}$-glucans, indicating that ${\beta}$-glucans reacts with dectin-1 receptors. We examined whether the aforementioned cytokines were involved in the signaling pathway from the dectin-1 receptor to phagocytosis, and found that the inhibition of iNOS, eNOS, and TNF-${\alpha}$ receptors significantly decreased ${\beta}$-glucan-induced phagocytosis. In conclusion, our study showed that dectin-1 signaling, triggered by ${\beta}$-glucans, subsequently elicited TNF-${\alpha}$ and NO-iNOS/eNOS production, and that these molecules seem to act as secondary molecules that cause eventual phagocytosis by macrophages. These findings suggest that C. versicolor could be used as a nutritional medicine that may be useful in the treatment of infectious disease.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.394-401
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• 2019

Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogenactivated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of $p38{\alpha}$ MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.