• Microbiology and Biotechnology Letters
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• v.38 no.1
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• pp.93-104
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• 2010

In this study, we investigated the effects of frankincense essential oil (BSEO) on the immune cell change in the lung, BALF and PBMC using a mouse model of asthma. BALB/c mice after intraperitoneal OVA sensitization (day 1) were challenged intratracheally with OVA on day 14. Then, the asthma was induced by repeated OVA inhalation challenged. The asthma induced mice group inhaled 0.3% BSEO for 30 minutes per trial, three times a week, for 8 weeks using the nebulizer. After 12 weeks from the experiment, the mice was killed and the lung, bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cell (PBMC) were obtained. Next, the change of immune cells inside the separated tissues was observed to identity the effects of BSEO on the allergic asthma mice. In conclusion, the hypersensitive reaction of airway to the bronchoconstrictor in the allergic asthma induced mice was effectively suppressed in Frankincense group, in Bermagot, Eucalyptus, Chamomile, Marjoram and Frankincense groups, the natural aromatic essential oil groups. Furthermore, it was also confirmed that the weight of lung, total number of alveolus cells and the number of BALF, MNL and DLN increased after inducing allergic asthma were reduced. BSEO suppressed the percentage of $CD3e^+/CD19^-$, $B220^+/CD23^+$ and $CD11b^+/Gr-1^+$ cells in the lung tissue of allergic asthma mice. Moreover, BSEO also reduced the percentage of $CD4^+/CD8^-$, $B220^+/CD23^+$ and $CD3^+/CCR3^+$ cells in BALF. In addition, the percentage of $CD3e^+/CD19^-$, $CD3^+/CD69^+$ and $B220^+/CD23^+$ cells in PBMC was reduced. The results of this study indicate that BSEO would be effective to treat allergic asthma by the immune control suppressing the activity of immune cells in each tissue.

• The Journal of Dong Guk Oriental Medicine
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• v.7 no.1
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• pp.33-41
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• 1998

Lymph node tissues of BALB/C mouse treated with DNCB were immunohistochemically observed to investigate the activation of cell mediated immunity in lymph node of murine with allergic contact dermatitis. The inguinal region of BALB/C mice were sensitized by one application of $25{\mu}l$ of 5% 2,4-dinitrochlorobenzene(DNCB) onto an abdominal skin and 2 weeks later, the mice were challenged with $4{\mu}l$ of 2.5% DNCB. The inguinal lymph node were obtained at hour 24, 48, and 72 after 2nd DNCB treatment and embedded with paraffin, and then stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly2(CD8), IL-2R(CD25). The distribution of helper T lymphocytes, cytotoxic T lymphocytes and IL-2 receptors began to increase at hour 24 after after 2nd DNCB treatment and these increase appeared in paracortical area and medullary sinius. These increase were greatest at hour 48. These results indicated that the IL-2 secretion began to increase by activation of helper T lymphocytes in lymph node of DNCB re-exposure area and subsequently to activate suppress T lymphocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1241-1245
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• 2015

Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.3
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• pp.71-85
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• 2014

Objectives In this study, we investigated the inhibitory effects of Samhwangsasim-tang (S.H) on the allergic response caused by ovalbumin(OVA) sensitization and challenge in BALB/c mice. Methods The experimental animals were divided into five groups; 1) normal as negative control, 2) OVA-sensitized mice, 3) OVA-sensitized mice treated with 200 mg/kg of S.H 200, 4) OVA-sensitized mice treated with 400 mg/kg of S.H 400, and 5) OVA-sensitized mice treated with 5 mg/kg of Dexamethasone (Dex). Antigen sensitization for allergic mouse model was performed with twice injection of OVA for 2 weeks. After secondary injection, S.H was administrated orally into mice every day for 13 days and the inhibitory effect of S.H on allergic responses was evaluated. Results Treatment of S.H into allergic mice reduced significantly ear edema and infiltration of immune cells in ear tissues induced with OVA challenge in a dose-dependent manner. S.H reduced significantly the serum levels of Total Immunoglobulin(Ig)G and IgE, and particularly inhibited the production of OVA-specific IgE, but not OVA-specific IgG. The serum level of proinflammatory cytokine TNF-${\alpha}$ and Th2-associated cytokine IL-4 also were significantly decreased by S.H adminstration in a dose denpendent manner. S.H attenuated OVA-induced secretion of IFN-${\gamma}$, but not IL-12 which is a cytokine inducing the development of Th1 cells. It also reduced significantly the secretion of IL-4, which is a cytokine inducing the development of Th2 cells, after splenocytes were stimulated with OVA. However the secretion of IL-5 and IL-13 was influenced weakly or a little. Conclusions These results indicate that S.H could reduce the allergic response through inhibition of antigen-specific IgE and Th2-inducing cytokines. It suggest that S.H may be available clinically for the treatment of allergic patients.

• Journal of Acupuncture Research
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• v.18 no.1
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• pp.157-169
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• 2001

Objective : The purpose of this study is to investigate the effects on WBC counts and each differential of neutrophils, lymphocytes, monocytes in whole blood sample of each experimental Aqua-acupuncture treated mice groups PCortex Ulmi Pumilae(CU), Ramulus Cinnamomum(RC), Radix Achyranthes(RA), Apitoxin(BV), Calculus Bovis Fel Ursi Moschus compound(BUM). Materials & Method : All the BALB/c mice used in this study were bred and maintained in our pathogen-free mouse facility and were 6 weeks of age at the start of the experiment. The experimental model of arthritis was induced by injecting 300${\mu}g$/kg LPS to all mice knee joint. The each of Aqua-acupuncture(Cortex Ulmi Pumilae, Ramulus Cinnamomum, Radix Achyranthes, Apitoxin, Calculus Bovis Fel Ursi Moschus compound) was injected into GB34(陽陵泉) of mice groups every other day for 6 times. And the WBC counts and each differential of neutrophils, lymphocytes, monocytes were measured at the 3rd, 7th and 14th day after LPS injection. Results : 1. The WBC counts were significantly decreased compared with the control(CON) group in every Aqua-acupuncture groups at all days. And at the 14th day, BV & BUM groups were more significantly decreased than RA group. 2. The Neutrophil's ratio was significantty increased compared with the CON group in CU & RC groups at the 3rd day and RC group was more significant than CU group. But at the 7th and 14th day, every Aqua-acupuncture groups were significantly increased compared with the CON group and at the 7th day, RC group was more significant than RA, BV & BUM groups and at the 14th day, RC, BV & BUM groups were more significant than RA group. 3. The Lymphocyte's ratio was significantly decreased compared with the CON group in RC group at the 3rd day. At the 7th day, CU, RC & BV groups were significantly decreased compared with the CON group. At the 14th day, every Aqua-acupuncture groups were significantly decreased compared with the CON group and RC group was more significant than RA group, 4. The Monocyte's ratio was significantly decreased compared with the CON group in every Aqua-acupuncture groups at the 7th day. At the 14th day, BV & BUM groups were significantly decreased compared with the CON group. Conclusion : According to the above results, it was concluded that CU & RC groups were more effective at the early period of this experiment, and at the latter period, BV & BUM groups were more effective than others. RA group was less effctive than others.

• Clinical and Experimental Pediatrics
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• v.54 no.9
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• pp.373-379
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• 2011

Purpose: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, $IgG_1$, and $IgG_{2a}$ levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific $IgG_1$ levels and increased serum $IgG_{2a}$ level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.217-222
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• 2014

Lonicerae Flos containing formulation, Geumeumyoungji-tang (GYT), is an herbal prescription prepared using 5 different herbal drugs, namely, Lonicerae Flos, Ganoderma, Lactucae Herba, Xanthii Fructus, and Smilacis Rhizoma. This study was focused on the investigation of the pharmacological effects of GYT on allergic reactions. As the first step of the study, GYT was administered BALB/c mice which were sensitized by 2,4-dinitrofluorobenzene (DNFB). As the result GYT ameliorated dermatitis provoked by DNFB. The serum IgE level of the DNFB sensitized-mouse was significantly decreased when GYT was administered. In order to confirm the moderating effect of this prescription on allergic reaction, GYT was pretreated to human mast cells (HMC-1) before they were stimulated by phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI). GYT suppressed secretion of inflammatory cytokines, interleukin (IL)-6 and IL-8, from HMC-1. Additionally, pretreatment of GYT showed regulating effect on COX-2 expression. Collectively, these findings provide insights into the pharmacological actions of GYT as a potential agent for treatment of allergic dermatitis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.8
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• pp.1100-1105
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• 2012

Green tea intake is known to have preventive effects against cancer. In this study, we evaluated the tumor suppressive effects of dietary green tea extracts (GTE) as a modulator on cisplatin in an established colon cancer mouse model. The cisplatin-induced cytotoxicity was determined with cell viability of the mouse colon cancer cell line (CT26) in vitro. The influence of GTE on the anti-tumor activity of cisplatin was evaluated by measuring tumor size with digital calipers in mice bearing CT26 colon carcinomas. The CT26 cell viability decreased to 93% at a $20{\mu}g/mL$ concentration of cisplatin. However, cell viability decreased to 15% with a combination of $20{\mu}g/mL$ cisplatin and GTE ($75{\mu}g/mL$). There were no apparent changes in cisplatin-induced cytotoxicity with GTE and epigallocathechin gallate (EGCG) treatments. Tumor size decreased in dietary GTE combining intra-peritoneal cisplatin-injected tumors bearing mice compared with cisplatin or GTE alone administered to tumor-bearing mice. These experiments showed that dietary GTE has a potentiating effect on the cisplatin anti-tumor activity of an established mice colon cancer model. Therefore, the GTE may be a candidate for modulators in anticancer treatments with cisplatin.

• Herbal Formula Science
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• v.19 no.1
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• pp.207-217
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• 2011

Objectives : In a previous study, we have shown that Gagam-Gongjin-Dan(GGD) has an inhibitory effect on the ovalbumin-induced immune responses and a hepatoprotective effect on actaminophen-induced liver injury in Balb/c Mice. However, the possible anti-inflammatory effect of GGD extract for inflammatory mediators was not reported. Therefore, the purpose of this study was to investigate an inhibitory effects of GGD extract against lipopolysaccharides(LPS) induced inflammatory mediators in mouse peritoneal macrophages. Methods : GGD extract was prepared by extracting with methanol for 7 days. The extract was freeze-dried following filtration through vacuum distillation system. Accumulated nitrite, an oxidative product of nitric oxide(NO), was measured in the culture medium by the Griess reaction. The levels of prostaglandin $E_2(PGE_2)$, interleukin-$1{\beta}$(IL-$1{\beta}$), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were measured by enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2) were measured by Western blot analysis. Results : GGD extract (50-$400\;{\mu}g$/ml) per se had no cytotoxic effect in LPS-stimulated peritoneal macrophages. GGD extract dose-dependently reduced NO, $PGE_2$, IL-$1{\beta}$ and TNF-${\alpha}$ production and COX-2 activity caused by stimulation of LPS. The levels of iNOS and COX-2 protein expressions were markedly suppressed by the treatment with GGD extract in a dose dependent manner. Conclusions : These results suggest that GGD extract has an anti-inflammatory effect against LPS-induced inflammatory mediators in peritoneal macrophages, these properties may contribute to inflammation disease care.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.2
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• pp.65-81
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• 2016

Objectives : Haedoksamul-tang (HSTE), a water extract from a mixture of Phellodendri Cortex, Coptidis, Scutellariae Radix, Gardeniae Fructus, Angelica acutiloba Radix, Cnidii Rhizoma, Paeoniae Radix, Rehmanniae Radix, has been traditionally used for allergic skin diseases such as atopic dermatitis and contact dermatitis in oriental countries. However, little is known about the effects of aqueous extract of HSTE on trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS) in a mouse model. Methods : In this study, we investigate the pharmacological effects of HSTE on TMA-induced CHS in Balb/c mice. Contact hypersensitivity was induced in mice by topically sensitizing and challenging with TMA in flank skin and ears during oral administration (for 17 days) and topical treatment (30 min before challenge) with HSTE. We examined the effects of HSTE on IgE and IgG1 levels, inflammatory parameters in ear tissues, CD4⁺/CD8⁺ ratio, cytokine and chemokine production in sera, tissues, and immune cells from TMA-sensitized mice.Results : Oral and topical administration with HSTE reduced, in a dose dependent manner, thickness and leukocyte infiltration of ear tissues and IgE levels in serum from mice sensitized with TMA. In addition, auricula lymph node cells isolated from TMA-sensitized mice significantly elevated the expression ratio of CD4⁺/CD8⁺ as well as increased the production of IL-4, IL-5, IL-13 and IFN-γ by ex vivo stimulation with antibodies against CD3 and CD28, and these inflammatory indexes, except for IFN-γ, were significantly suppressed by orally and topically administration of HSTE. Furthermore, stimulation of auricula lymph node cells from TMA-sensitized mice with antibodies against CD3 and CD28 increased the production of MCP-1/CCL2 and MIP-1α/CCL3, and these effects were inhibited in a dose-dependent manner in cells from mice treated with HSTE. Conclusions : These results suggest that HSTE can be used for treating contact hypersensitivity by inhibiting leukocyte infiltration as well as production of serum IgE and chemokine/Th2 cytokine in an animal model.