• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.3
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• pp.349-354
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• 2014

Elevation of intracellular calcium ($Ca^{{+}{+}}$) triggers degranulation of mast cells by bypassing receptor activation. Flos Sophora japonica L. has been used as a natural dying source and has been reported to have biological activities such as anti-inflammatory and anti-allergic effects through $Fc{\varepsilon}RI$ and IgE crosslinking. In the present investigation, we report the regulatory effect of ethanolic extract of Flos Sophora japonica L. (S.F) on allergic mediators produced by $Ca^{{+}{+}}$ ionophore activation in mast cells. S.F significantly inhibited calcium ionophore (A23187)-induced interleukin (IL)-4 and tumor necrosis factor (TNF)-${\alpha}$ production as well as mast cell degranulation. Furthermore, administration of S.F suppressed allergic reactions in a 2,4-dinitrofluorobenzene (DNFB)-induced allergic dermatitis mouse model. Both oral administration and ear painting using 50 mg/kg of S.F significantly reduced levels of cytokines such as IL-4, TNF, and interferon-${\gamma}$ in ear tissues compared to the DNFB alone-treated group. Serum IgE level in the S.F-treated group also decreased compared to the DNFB alone-treated group. Weights of spleens and lymph nodes in the S.F-treated groups also decreased compared to the control group. Considering the data, we conclude that S.F mediates its anti-allergic effects not only through $Fc{\varepsilon}RI$ stimulation but also $Ca^{{+}{+}}$ influx in mast cells.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.449-458
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• 2003

Background : The poor prognostic factors of far-advanced pulmonary tuberculosis(FAPTB) are lymphocytopenia in the peripheral blood(PB)(< $1,000/mm^3$) and $T_4$-cell count ${\leq}500/mm^3$. However, the cause of PB lymphocytopenia in FAPTB is unclear. The aim of this study was to analyze the lymphocyte proportion and cytokines of the bone marrow(BM) in FAPTB patients with peripheral lymphocytopenia in order to clarify whether the limiting step of the lymphocytopenia occurs in production, differentiation, or circulation. Methods : This study included patients with FAPTB between August 1999 and August 2002 who visited Gachon Medical School Gil Medical Center. The exclusion criteria were old age(${\geq}65years$), cachexia or a low body weight, shock, hematologic diseases, or BM involvement of tuberculosis. The distributions of cells in PB and BM were analyzed and compared to the control group. The interleukin(IL)-2, IL-7, IL-10, TNF-${\alpha}$, Interferon-${\gamma}$, and TGF-${\beta}$ levels in the BM were measured by ELISA. Result : Thirteen patients(male : female=9:4) were included and the mean age was $42{\pm}12$years. The proportion and count of the lymphocytes in the PB were significantly lower in the FAPTB group ($7.4{\pm}3.0%$, $694{\pm}255/mm^3$ vs. $17.5{\pm}5.8%$, $1,377{\pm}436/mm^3$, each p=0.0001 and 0.002). The proportion of immature lymphocyte in the BM showed a decreasing trend in the FAPTB group($9{\pm}4%$ vs. $12{\pm}3%$, p=0.138). The IL-2($26.0{\pm}29.1$ vs. $112.2{\pm}42.4pg/mL$, p=0.001) and IL-10($3.4{\pm}4.7$ vs. $12.0{\pm}8.0pg/mL$, p=0.031) levels in the BM were significantly lower in the FAPTB group than those in control. The levels of the other cytokines in FAPTB group and control were similar. Conclusion : These results suggest that the cause of lymphocytopenia in PB is associated with a abnormality IL-2 and IL-10 production in the BM. More study will be needed to define the mechanism of a decreased reservoir in BM.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.574-579
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• 2008

Propolis is the generic term for the resinous substance collected by honey bees from a variety of plant sources. In this study, we have assessed the immunomodulatory properties of propolis (P) and fermented-propolis (FP) in BALB/c mice. Mice were subjected to gavage once a day (for 14 days) with 50, 100, 200 mg/kg body weight P, FP, or vehicle. Lymphocytes were isolated from the spleen and mesenteric lymph nodes (MLN) and the immune cell proportions, proliferative activities, and cytokine production were evaluated. The P- and FP-administration induced similar, but differential, alterations in the percentage of immune cell populations and their biological functions, including cytokine production and NK cell cytotoxicity. The proportion of$ CD4^+$ and $CD8^+$ T cells in the spleen was increased slightly in the P- and FP-administered mice as compared to the vehicle-treated mice. In MLN, the percentage of $CD4^+$ T cells was increased significantly in the 200 mg/kg P-treated mice. The mice which were treated with P and FP evidenced significantly increased interferon-$\gamma$ and interleukin-4 production in concanavalin A-stimulated splenocytes, whereas the production of theses cytokines was not shown to be induced by P-treatment. In addition, NK cell activity was also increased dramatically by the administration of P and FP. Collectively, these findings showed that P and FP are wide-spectrum immunomodulators, which may modulate both innate and adaptive immune responses.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.115-122
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• 2012

Objectives : This study evaluated activities and ingredient contents concerning extracts according to extraction solvents of Insampaedok-san (IS, Renshen bai du-san). Methods : The herbal constituents of IS were extracted with water and 70% ethanol at $100^{\circ}C$ for 2 hr. Using the HPLC system, the six ingredient contents of different solvent extracts of IS were analyzed. The nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) production and proinflammatory cytokines were measured in RAW264.7 cells stimulated with lipopolysaccharide (LPS). The macrophage-derived chemokine (MDC/CCL22) and regulated on activation normal T-cell expression and secreted (RANTES/CCL5) production were measured in HaCaT and BEAS-2B cells stimulated tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). The activities of glycerol-3-phosphate dehydrogenase (GPDH) and leptin level were measured in 3T3-L1 cells. Results : The calibration curves showed good linearity ($r^2$=1.0000) for different concentration ranges. The contents of liquiritin, naringin, hesperidin, neohesperirin and glycyrrizin in 70% ethanol extracts of IS were relatively higher than that of water extract, however the content of ferulic acid in 70% ethanol and water extract of IS were similar. The extraction solvents of water and 70% ethanol were evaluated inhibitory effect on the production of NO, $PGE_2$, TNF-${\alpha}$ and IL-6 in RAW 264.7 cells. Their extractions were inhibitory effect on production of MDC/CCL22 and RANTES/CCL5 in HaCaT cell and BEAS-2B cell, respectively. In addition, evaluated reduced on GPDH activity and leptin level in 3T3-L1 preadipocyte cell. Conclusions : Our results suggest that IS extracts were inhibitory effects of disease such as inflammation, allergies and obesity.

• Journal of Pharmacopuncture
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• v.20 no.2
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• pp.107-111
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• 2017

Objectives: Radiation is one of the most important sources of free radical (such as reactive oxygen species) production, which plays an essential role in the etiology of over hundred diseases. The aim of the study was to investigate some immune parameters and hematological indices in healthy workers of the Radiology Department, University Hospital of Mashhad, Iran. Methods: The study was performed on 50 healthy workers: 30 radiology staff as the case group and 20 laboratory workers as the control group. The radiation dose received by the radiology staff participating in the study was less than the annual maximum permissible level, 50 millisievert. Hematological parameters, lymphocyte proliferation and cytokine production were studied in both groups. Results: Among healthy radiology workers, the hematological indices did not differ statistically; however, their proliferation indices and $IFN-{\gamma}$ levels showed significant increases in parallel with decreases in the IL-4 levels as compared to controls. The immune system of workers exposed to low-dose ionizing radiation was found to be shifted from a Type 2 to a Type 1 response to promote cellular immunity. Conclusion: Based on our data, exposure to low-dose ionizing radiation may decrease the prevalence, frequency, and recurrence of various cancers and infectious diseases because of an increase in Th1-cell-based response, thus leading to more protection of the human body against tumor cells and foreign agents and possibly increased longevity. However, due to high rate of fluoroscopy use for interventional radiology, we suggest continuing research projects on radiation protection and hazards to prevent irreversible damage. As a recommendation, in future studies, radiology staff with a weakened immunity due to high radiation exposure should be considered as good choices to be treated using acupuncture techniques because acupuncture has been demonstrated to enhance the function and the number of immune cells.

• Journal of Nutrition and Health
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• v.37 no.6
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• pp.431-439
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• 2004

Scutellariae Radix (Scu.), one of the immune-regulatory substances, is recognized to play the role in the metabolic process of inflammation, allergy and immunity. It has been traditionally used in the Oriental medicine to treat inflammatory bowel diseases (IBD). The purpose of this study was to evaluate the effects of water extracts of Scutellariae Radix on the spleen lymphocyte immune function in the Balb/c female mice treated with dextran sodium sulfate (DSS) to induce colitis. Water extract of Scutellariae Radix (100 mg/kg) and sulfasalazine (50 mg/kg) were administrated orally for 2 weeks of experimental period. Mice were divided into three experimental groups randomly: DSS group (5％ DSS was ad libitum for 5 days) as control group, DSS ＋ Scu. (water extracts of Scutellariae Radix for 2 weeks after 5％ DSS was ad libitum for 5 days) as experimental group, and DSS ＋ Sulfasalazine group (Sulfasalazine for 2 weeks after 5％ DSS was ad libitum for 5 days) as positive control group. Levels of Ig A, Ig E, CD4$^{＋}$, CD8$^{＋}$, TNF-$\alpha$ and other cytokines were measured. Treatment of DSS for 5 days induced bowel inflammation and the treatment with Scu. water exteract and sulfasalazine significantly recovered the damage. The length of intestine of DSS group was significantly shorter than that of other groups. The serum and fecal concentration of Ig A of SS ＋ Scu group was higher than those of DSS group. The contents of CD4$^{＋}$ T cells was higher in the DSS ＋ Scu. group than the other groups and CD8$^{＋}$ T cells was the lowest in DSS ＋ Sulfasalazine group. The Ig A level of cultured supernatant of spleen lymphocyte was the highest, while the Ig E level was the lowest in SS ＋ Scu group. The concentration of TNF-$\alpha$, cytokine secreted from the Th1 cell in the supernatant spleen lymphocyte, was the highest in the DSS group and the lowest in the DSS ＋ Scu. group. The concentration of IFN-${\gamma}$ and ll...-12 was lower in the DSS ＋ Scu. group than those of the other groups. The concentration of IL-4 in the supernatant of spleen lymphocyte was the lowest in the DSS ＋ Scu. group but IL-10 was not significantly different. Based on these findings, water extract of Scutellariae Radix exhibited the inhibitory effect via IL-4 production thereby inhibited the production of Ig E and strengthened immune system, and alleviated injury in DSS- induced colitis mice model.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.4
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• pp.1-29
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• 2014

Objectives Dictamni Radicis Cortex extracts (DRC) has been known to suppress allergic reaction, however the cellular target of DRC and its mode of action remain unclear. The purpose of this study is to investigate the effects of Dictamni Radicis Cortex extracts on DNCB induced atopic dermatitis-like skin lesions of NC/Nga mouse. Methods This study was designed to investigate the effects of DRC extract in the DNP-IgE-induced activation of MC/9 murine mast cell lines in vitro and in the DNCB-induced activation of NC/Nga mouse in vivo. For this investigation, We examined IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF mRNA expression by Real-time PCR, IL-13, MIP-$1{\alpha}$ production by ELISA analysis and manifestations of NFAT1, NFAT2, AP-1 and NF-${\kappa}B$ p65 transcription factors by western blotting in vitro. Then, we examined WBC, eosinophil and neutrophil in NC/Nga mouse, IL-5, IL-13 in serum, IFN-${\gamma}$, IL-4 in the spleenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $^+Gr-1^+CD11b$, $B220^+CD23^+$ in the ALN, PBMCs and dorsal skin, IL-5, IL-13 in the dorsal skin by Real-time PCR and the distribution of mast cells by H&E and toluidine blue. Results In vitro the mRNA expression of IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$, GM-CSF and IL-13, MIP-$1{\alpha}$ production by ELISA analysis were completely abolished by DRC and the western blot analysis decreased the expression of mast cell-specific transcription factors including NFAT-1, NF-${\kappa}B$ p65. In vivo DRC oral adminstration also decreased the counts of WBC, eosinophils and inflammatory cytokines such as IL-13 and IgE in the serum. DRC oral adminstration elevated IL-4 level in the spleenocyte culture supernatant. DRC oral adminstration decreased total ALN cells, total skin cells, cell numbers of $CD4^+$, $B220^+CD23^+$ in the ALN, $^+Gr-1^+CD11b$ in the PBMCs and $CD4^+$, $CD8^+$ in the dorsal skin. The mRNA expression of IL-5, IL-13, thickness of epidermis, inflammation immune cells and mast cells were abolished by DRC in the dorsal skin. Conclusions Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mouse were much improved by DRC oral adminstration. These results, therefore, suggest that DRC can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis induced in NC/Nga mouse, and may play an important role in recovering AD symptoms.

• Journal of Haehwa Medicine
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• v.19 no.2
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• pp.119-137
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• 2011

In order to improve efficacy of oriental medicines and to study the application of fermented oriental medicine in clinicals, the efficacy of CYT and CYTBH on atopic dermatitis were evaluated. The results and conclusions are as follows. CYT and CYTBH significantly improved the atopic dermatitis symptoms in NC/Nga mice by naked eye evaluation and significantly decreased clinical index in both groups. CYT and CYTBH both decreased the cell numbers of CD3+, CD11b+Gr-1+ cells in dorsal skin. Of the cells, CYT significantly decreased CD11b+Gr-1+ cells whereas CYTBH significantly decreased all immune cells. CYT and CYTBH both decreased the production rate of IL-4 and IFN-${\gamma}$ activated by CD3/CD28. In the case of CYTBH, significant decrease in all cases was observed. CYT and CYTBH decreased the production rate of IL-5, IL-13 and IL-17 in serum. Significant decrease of IL-5 in the case of CYT and IL-5 and IL-13 in the case of CYTBH were observed. CYT and CYTBH significantly decreased transcription of IL-5 mRNA and IL-13 mRNA in skin. Significant decrease in IgG1 and IgE immunoglobulins in serum were oberved in both groups. Significant decrease was only observed in the case of CYTBH. Both CYT and CYTBH significantly decreased the secretion of histamine. Both CYT and CYTBH suppressed erythema, hemorrhage, edema, excoriation, erosion of skin tissues of NC/Nga mice resulting in the decrease of thickness of epidermis. Significant decrease of infiltration of obese cells was also observed. The results above indicated that both CYT and CYTBH had significant efficacy in the treatment of atopic dermatitis through immune modulation. Animal studies showed that CYTBH had superior activity than that of CYT suggesting further and continuous studies on the changes in ingredients or absorption improvement by fermentation should follow.

• Food Science of Animal Resources
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• v.31 no.5
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• pp.701-709
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• 2011

This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4, 37, 60, 80, and $100^{\circ}C$) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at $80^{\circ}C$ for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 ${\mu}M/10^5$ cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-$1{\beta}$ (IL-$1{\beta}$) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-${\gamma}$ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.883-908
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• 1997

Bone remodeling is characterized by the coupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. The process is tightly regualted at the local level by an incompletely known netwotk of peptide and non-peptide fators. Nitric oxide(NO), synthesized by nitric oxide synthetase(NOS) from L-arginine, is becoming recognized as an important bioregualtory molecule in a variety of tissue, but little is known about its possible role in periodontal tissue. The purpose of this study is to investigate the expression of nitric oxide synthetase(NOS) in inflamed gingiva and the effects of cytokine on the expression of NOS protein. The expression of NOS in gingival tissue was evaluated by immunohistochemical staining for $NOS_1$, $NOS_2$, $NOS_3$. The effect of cytokine on the expression of NOS in human periodontal ligament cells and osteoblast-like HOS cells by western blot analysis. Further, we studied that NO functions in periodontal ligament cells as a regulatory molecule. PDL cells incubated with NOS inhibitor and donor. The protein expression, type I collagen & non-collagenous protein, nitrate production and cell proliferation were evaluated The results were as follows. 1. $NOS_1$, $NOS_2$, $NOS_3$ was rarely distributed in healthy gingiva, but stronger stained in gingival epithelium, endothelial cells, and mononuclear cells of inflammed gingiva. 2. The cytokine stimulated $NOS_1$, and $NOS_3$ protein were not inducing or inhibitory effect to compared with control in PDL and HOS cells. 3.Incubation of cells with combination of $TNF-{\alpha}$, $IFN-{\gamma}$, LPS result in a time dependant increase in $NOS_2$ expression, reaching a maximal level after 24 hours of stimulation. 4. The osteonectin protein inhibitory effect of NMA, inhibitor of NOS, was reversed by Larginine in dose dependant manner. 5. NMA decreased cell poliferation and nitrate production, but the inhibitory efffect of NMA was also prevented by the NO donor, sodium nitropruiside. These results suggest that exogenously synthesized NO was playing a stimulating effect on cell proliferation or on non-collagenous protein expression. Therefore NO have an important role in mediation of localized bone destruction associated inflammatory bone disease such as periodontitis.