• Journal of Food Hygiene and Safety
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• v.37 no.1
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• pp.29-37
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• 2022

This study will evaluate the effect of fermented Morinda citrifolia L. extracts and its marker compounds to provide baseline data for utilizing Morinda citrifolia L. as functional health products. Morinda citrifolia L. and six marker compounds were processed on RAW 246.7 macrophage to test for XTT Cytotoxicity, measure Nitric Oxide and Cyokine formation, and analyze the expression of immune marker genes. Furthermore, LPS and fermented red ginseng extract, a common functional ingredient, are used as positive controls. Our results showed that fermented Morinda citrifolia L and six bioactive compounds did not have any cytotoxic effect in all treatment concentrations and groups. Among six bioactive compounds, SCP and ASE confirmed the formation of NO. In addition, the ASE treatment group showed increased formation of IL-6 and IL-1β and the expression of iNOS and TNF-α. Also, fermented Morinda citrifolia L extract activated the macrophage by enhancing the production of nitric oxide (NO), interleukin (IL)-6, and IL-1β, and the expression of COX2 compared to Morinda citrifolia L. extracts. The result of the study showed that Fermented Morinda citrifolia L. (Noni) and marker compound enhance the innate immunity activity and suggested that the bioactive compound could be applied as a marker compound. Thus, Fermented Morinda citrifolia L. (Noni) could be used as functional food material to develop immunity-enhancing products, and highly functional marker compounds can be utilized as the effective components.

• BMB Reports
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• v.48 no.6
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• pp.336-341
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• 2015

Sepsis is a life-threatening, infectious, systemic inflammatory disease. In this study, we investigated the therapeutic effect of α-cubebenoate, a novel compound isolated from Schisandra chinensis against polymicrobial sepsis in a cecal ligation and puncture (CLP) experimental model. Administration of α-cubebenoate strongly enhanced survival in the CLP model. α-cubebenoate administration also markedly blocked CLP-induced lung inflammation and increased bactericidal activity by enhancing phagocytic activity and hydrogen peroxide generation in mouse bone marrow-derived macrophages and neutrophils. Expression of two important inflammatory cytokines, IL-1 and IL-6, was strongly increased in the CLP model, and this was dramatically blocked by α-cubebenoate. Lymphocyte apoptosis and caspase-3 activation, which are associated with immune paralysis during sepsis, were markedly attenuated by α-cubebenoate. Taken together, our findings indicate that α-cubebenoate, a natural compound isolated from Schisandra chinensis, is a powerful potential anti-septic agent. [BMB Reports 2015; 48(6): 336-341]

• Korean Journal of Plant Resources
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• v.34 no.4
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• pp.377-383
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• 2021

In this study, we investigated in vitro immunostimulatory activity of fruit extracts from Pyrus ussuriensis var. hakunensis (Nakai) T.B. Lee (PUF) using mouse macrophage RAW264.7 cells. PUF increased the production of immunostimulatory factors such as NO, iNOS, IL-1β, IL-6 and TNF-α, and phagocytic activity in RAW264.7 cells. The inhibition of TLR2 and TLR4 blocked PUF-mediated production of immunostimulatory factors in RAW264.7 cells. In addition, the inhibition of MAPKs signaling pathway reduced PUF-mediated production of immunostimulatory factors. From these results, PUF may have immunostimulatory activity via TLR2/4-mediated activation of MAPKs signaling pathway. Therefore, PUF expected to be used as a potential immune-enhancing agent.

• Advances in Traditional Medicine
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• v.5 no.3
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• pp.216-230
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• 2005

Although the field of study in immune enhancing compounds is relatively new, natural products from plants represent a rich and promising source of novel molecules with immunomodulating properties, Microglial cells, the main immune effector cells of the brain, usually display a ramified morphology and low expression levels of immunologically relevant antigens such as MHC class I and class II. Since any compound which participates in activation of phagocytic cells contributes to the production of potentially toxic factors, the search for convenient in vitro test-systems and study of mechanisms of action of these agents are of great interest. Human blood polymorphonuclear (PMN) cells and primary microglial cells isolated from Sprague-Dawley rats were used as cellular screening tests for study of phagocytosis-stimulating action of immunomodulating agents. Numbers of phagocytic activity were evaluated by the phagocyte ingestion of yeast cells and NO-synthase activity, nitrite production, and nitroblue tetrazolium test were determined after phagocyte stimulation. It was possible to demonstrate that indexes of phagocytic activity can be used as quantitative indicators for measurement immunomodulating activity. As a positive control, Zymosan A-induced phagocytosis in both PMN cells and primary microglial cells was used. $IFN-{\gamma}$ (0.1 -1 U/ml) stimulated phagocytosis in PMN cells 1.2 times after 2 - 3 h incubation, although at higher concentrations (10 - 100 U/ml) it strongly inhibited phagocytosis. In a similar way, at higher concentrations, $IFN-{\gamma}$ (100 - 500 U/ml) suppressed phagocytosis in zymosan-A stimulated microglial cells. When Polypodium leucotomus, cambricum and vulgare extracts were tested alone, increased levels of phagocytosis were observed in PMN. In addition, microglial cells showed both increased phagocytosis and MHC class-II antigen expressions. Surprisingly, when PMN and microglia were treated with a combination of Polypodium and $IFN-{\gamma}$, phagocytosis was not inhibited. We did not find changes in NO-synthase activity and nitrite production in both microglia and PMN cells activated by different immunomodulating agents. These results indicate that primary microglial cell cultures as well as human PMN cells can provide reproducible quantitative results in screening phagocytic activity of different immunoactive compounds. Furthermore, both inhibitory or activation mechanisms might be studied using these in vitro experimental approaches.

• Ocean and Polar Research
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• v.32 no.2
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• pp.157-164
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• 2010

A marine alga, Spirulina maxima, was extracted under high pressure and low temperature conditions at 500 MPa and $60^{\circ}C$ for 5 and 10 min. A high pressure of 500 MPa was applied to improve process yields because of low temperature extraction. This method resulted in highest higher extraction yield of 26.1% (w/w) in comparison to those results obtained from conventional extraction methods which produced a yield of 17.6% (w/w) from water. The extracts from this process also showed 19% of low cytotoxicity against human normal fibroblast cells in adding 1.0 mg/ml of the highest concentration. The crude extract significantly reduced the production of Prostaglandin $E_2$ ($PGE_2$) from CCD-986sk cells and increased nitric oxide production by macrophages. These higher activities of enhancing skin immune functions were found to have high antioxidant extract properties, like a 98% increase in DPPH radical scavenging activity. The extracts from the high pressure process showed a higher elution of active components than other processes and generated new compounds based on HPLC analysis. This clearly indicates that the extracts from high pressure and low temperature conditions have higher skin immune activation properties that have not been previously reported.

• Journal of Acupuncture Research
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• v.24 no.6
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• pp.29-36
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• 2007

Electroacupuncture(EA) is known to affect various autonomic functions such as blood pressure regulation, immune modulation and the improvement of disorders concerning autonomic functions. The aim of the present study was to establish whether EA has an immune-enhancing effect. ICR mice weighing 20 to 25g were divided into four groups: Group I(n=6), blank; Group II(n=6), control; Group III(Zusanli, n=6), low frequency-EA(10Hz of electrical stimulation), and Group IV(Zusanli, n=6), high frequency-EA (100Hz of electrical stimulation). For this study, we investigated expressions of spleen heat shock protein (HSP)70, HSP90 and secretions of cytokines. A Forced Swimming Test(FST) was performed as a model of activity test in mice. After three days of the FST, 10Hz EA($114.8{\pm}7.27s$) and 100Hz EA($147.5{\pm}1.29s$) immobility time significantly decreased compared with the control group($157.2{\pm}1.48s$). After seven days, 10Hz EA($124{\pm}1s$) and 100Hz EA($141{\pm}4.24s$) also significantly decreased immobility time compared with the control group($168{\pm}7.93s$). 10Hz EA and 100Hz EA increased the expression of HSP70 but did not change that of HSP90. 100Hz EA increased secretions of IL-6 and IL-12 compared with the control group however, 10Hz EA failed to change those of IL-6 and IL-12. The present results suggest that EA may be useful for down-regulated immune diseases.

• IMMUNE NETWORK
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• v.4 no.2
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• pp.100-107
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• 2004

Background: The fruit of Rubus coreanus (RC), a perennial herb, has been cultivated for a long time as a popular vegetable. The anti-allergy mechanism of RC is unknown. The purpose of this study is to investigate the inhibitory effect of RC on compound 48/80- or anti-DNP IgE-induced mast cell activation. Methods: For this, influences of RC on the compound 48/80-induced degranulation, histamine release, calcium influx and the change of the intracellular cAMP (cyclic adenosine-3',5' monophosphate) levels of rat peritoneal mast cells (RPMC) and on the anti-DNP IgE-induced histamine release of RPMC were observed. Results: The pretreatment of RC inhibited compound 48/80-induced degranulation, histamine release and intracelluar calcium uptake of RPMC. The anti-DNP IgE-induced histamine release of RPMC was significantly inhibited by pretreatment of RC. The RC increased the level of intracellular cAMP of RPMC, and the pretreatment of RC inhibited compound 48/80-induced decrement of intracellular cAMP of RPMC. Conclusion: These results suggest that RC contains some substances with an activity to inhibit the compound 48/80- or anti-DNP IgE-induced mast cell activitation. The inhibitory effects of RC are likely due to the stabilization of mast cells by blocking the calcium uptake and enhancing the level of intracellular cAMP.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.1 no.1
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• pp.167-190
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• 1995

Bikiwhan is one of the oriental medicines that have been used for the treatment of tumors since ancient times. However, the mechanism of the drug action is not closely surved. This study was made to investigate the effects of Bikiwhan on the innate immunity were analysed by measuring the functions of phagocytes, and those of specific immunity were analysed by measuring T and B cells activities. The followings are the results obtained from this study : 1. Bikiwhan has direct cytotoxic effects against human lymphoma cell lines (K562) in a dose dependent manner. 2. An administration of Bikiwhan increased allogenic immune response in the mouse. 3. An administration of Bikiwhan increased the antibodies formation against SRBC. 4. An administration of Bikiwhan enhanced the apperance of rosette forming cells in the spleen. 5. An administration of Bikiwhan decreased the delayed-type hypersensitivity against dinitrofluorobenzene. 6. An administration of Bikiwhan has no effect on natural killer cells. 7. Bikiwhan increased the phagocyte activity of peritoneal macrophages in vitro and in in vivo as well. 8. Bikiwhan depressed the formation of reactive oxygen intermediated in vitro and in vivo as well. 9. Bikiwhan has the capacity to make peritoneal macrophages secrete nitric oxide. The above results demonstrate that Bikiwhan has enhancing effects of immune responses against tumors by decreasing tissue demages caused by immune responses.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.298-306
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• 2017

Background: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses. Methods: The immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes. Results: Compound K induced cell cluster formation through cell-cell adhesion, cell migration, and phagocytic activity, but it suppressed cell-tissue interactions in U937 and RAW264.7 cells. Compound K also upregulated the surface expression of the cell adhesion molecule cluster of differentiation (CD) 43 (CD43) and costimulatory molecules CD69, CD80, and CD86, but it downregulated the expression of monocyte differentiation marker CD82 in RAW264.7 cells. Moreover, CK induced the release of reactive oxygen species and induced messenger RNA expression of proinflammatory genes, inducible nitric oxide synthase, and tumor necrosis factor-alpha by enhancing the nuclear translocation and transcriptional activities of nuclear factor kappa-B and activator protein-1. Conclusion: Our results suggest that CK has an immunomodulatory role in innate immune responses through regulating various cellular events mediated by monocytes and macrophages.

• Korean Chemical Engineering Research
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• v.44 no.1
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• pp.87-91
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• 2006

Polysaccharides extracted from mushroom have been most commonly used to enhance the immune system. Also polysaccharides maintaining the moisture extent on epidermal tissue have an effect on the removal of necrotic tissue and the restoration of epidermal tissue through enhancing the immune system at skin layers. In this work, polysaccharides were from Schizophyllum commune studied about the burn and wound healing activity in the epidermal tissue on rats through in vivo experiment and hematological values. And antibacterial activities were examined using pathogenic microorganisms causing the secondary inflammation.