• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.439-448
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• 2021

DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4⁺ T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GM-CSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ⁺ Th1 cells, IL-4⁺ Th2 cells, IL-9⁺ Th9 cells, IL-17⁺ Th17 cells, and Foxp3⁺ Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.

• Journal of Microbiology and Biotechnology
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• v.33 no.3
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• pp.363-370
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• 2023

Atopic dermatitis (AD) is a chronic inflammation associated with skin hypersensitivity caused by environmental factors. The objent of this study was to assess the hot water extracts of Sargassum horneri (SHHWE) on AD. AD was induced by spreading 2,4-dinitrochlorobenzene (DNCB) on the BALB/c mice. The efficacy of SHHWE was tested by observing the immunoglobulin E (IgE), cytokine, skin clinical severity score and cytokine secretions in concanavalin A (Con A)-stimulated splenocytes. The levels of interleukine (IL)-4, IL-5 and IgE, the pro-inflammatory cytokines that are closely related, were notably suppressed in a does-dependent manner by SHHWE, whereas the level of interferon γ (IFN-γ), the atopy-related Th1 cytokine inhibiting the production of Th2 cytokines, was increased. Therefore, these results show that SHHWE has a potent anti- inhibitory effect on AD and is highly valuable for cosmetic development.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.125-134
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• 2010

Objective: The aim of this study was to measure the concentrations of cytokines contained in the hydrosalpingeal fluid and to evaluate the effect on the mouse embryo development with the different cytokine concentration. Methods: The hydrosalpingeal fluids (HSF) were collected during the surgery for hydrosalpinx which was confirmed by hysterosalphingogram. The cytokines in HSF including interleukin (IL)-$1{\alpha}$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, Interferon-$\gamma$ (IFN-$\gamma$), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), monocyte chemotactic protein-1 (MCP-1) were measured by ELISA method. HSF were added up to culture media with 5%, 10%, and 30% concentrations. The blastulation rates were compared. Results: IL-$\alpha$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, IFN-$\bamma$, VEGF, EGF, and MCP-1 were detected, but the concentrations were different from each sample. IL-6 and IL-10 were increased in HSF-1 group, and IFN-$\gamma$, MCP-1, VEGF were increased in HSF-2 compared with normal serum range. The Th1/Th2 ratio of HSF-2 (IFN-$\gamma$:IL10) was highly elevated to 61.64, compared with that of HSF-1 (3.69). The blastulation rate was significantly decreased in HSF-2 group (27.7%) compared those of the HSF-1 group (74%) and control group (76.7%). It showed the trend that the blastulation rate was decreased depending on the concentration HSF of culture media in HSF-2 group, but it was not statistically significant. Conclusion: The composition and concentration of cytokines in each HSF were different, and increased proinflammatory cytokines in HSF might be associated with poor embryonic development. Further study will be needed about the effect of each cytokines in HSF.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.1
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• pp.16-32
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• 2016

Objective : The water extract of Bojungikgi-tang (BTE) composed with Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Atractylodes Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Cimicifuga Rhizoma, and Bupleuri Radix and it has been traditionally used for chronic diseases or weakness after illness in oriental countries. However, little is known about the effects of aqueous extract of BTE on trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS). Therefore, the aim of this study was to investigate the effects of BTE on TMA-induced CHS in BALB/c mice.Methods : In this study, the extract of BTE was prepared by extracting with distilled water at 100℃ for 2.5 h. The extract was freeze-dried following filtration through 0.45 μm filter. Mice were orally administrated with or without BTE extract of different doses (25-200 ㎎/㎏/day) for 28 days. During the challenge period, mice were externally applied with different doses of BTE extract one time per day 30 min before TMA treatment. I examined the effects of BTE on the serum levels of IgE, IgG1, IgG2a, and IgG2b, nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in isolated peritoneal macrophages, Th2 cytokine production in isolated spleen cells, ear swelling responses, and the leukocyte infiltration induced by TMA.Results : The orally and externally administration of BTE dose-dependently reduced the serum levels of hapten-specific immunoglobulin E (IgE), IgG1 titer, and PGE₂ production as well as ear swelling responses and leukocyte infiltration in TMA-induced BALB/c mice. The levels of NO and PGE₂ production from peritoneal macrophages stimulated with TMA-BSA were markedly suppressed by pretreatment with BTE in a concentration dependent manner. Furthermore, the levels of Th2 cytokines (IL-4, IL-5, IL-13) production from spleen cells stimulated with ConA were markedly suppressed by BTE treatment in a concentration dependent manner.Conclusions : These results suggest that BTE treatment suppresses chronic contact hypersensitivity, and it can be assumed that the suppression of ear swelling, serum IgE, NO and PGE₂ levels, leukocyte infiltration, and Th2 cytokines in an animal model. Therefore, these properties may contribute to the strong anti-CHS response effect of BTE.

• YAKHAK HOEJI
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• v.57 no.1
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• pp.37-42
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• 2013

In this present study, we determined the immunoregulatory activity of ginsenoside Rd extract from Panax ginseng. To determine the activity, we tested Rd against $CD4^+$ Th cells in a murine model of type 1 diabetes, which involves Th1-dominant immunity. The type 1 diabetes was caused by streptozotocin (STZ) and the severity of the diabetes was evaluated by measuring the degree of hyperglycemia, a major symptom of diabetes. The data resulting from experiments showed that ginsenoside Rd induced a greater level of Th1 type cytokines [IFN-${\gamma}$ & IL-2] than Th2 type [IL-4 & IL-10] (P<0.05), which was determined by cytokine profile analysis. In the animal model of diabetes, the depletion of $CD4^+$ Th cells by a treatment of anti-CD4 mAb resulted in considerably lower values of blood-glucose levels than those of the mAb-untreated mice, which indicates that the Th1 immune response from $CD4^+$ Th cells are responsible for diabetes. Based on these observations, the effect of Rd on diabetes was examined in the same animal model. Results showed that Rd-treated mice groups had increased levels of blood glucose compared to Rd-untreated mice groups that were used as a negative control (P<0.05). In other words, Rd aggravated the diabetes via the Th1 immune response. In conclusion, ginsenoside Rd had an immunoregulatory activity of Th1-dominant immunity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.27 no.3
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• pp.84-95
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• 2014

Objective : Ephedra sinica (ES) has has been used as remedy of allergic diseases for a long time in Korea. In the present study, we investigated the anti-allergic effects of ES on experimental allergic asthma mouse model using ovalbumin (OVA). Methods : BALB/c mice were sensitized and challenged with 100 ug of OVA and 1 mg of aluminum potassium sulfate of 0.2 ml phosphate-buffered saline(PBS) intraperitoneally on day 1 and 15. mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 h after the last challenge. we examined the lung histology, airway hyper sensitivity, total inflammatory cell count in bronchoaveloar lavage fluid(BALF), Th2-associated cytokines production and IgE production. Results : ES potently inhibited the lung damage and the development of Penh. ES also reduced the number of BAL cells during OVA-induced allergic asthma. Furthermore, ES inhibited cytokines production such as IL-4, IL-13 productions, and IgE level of serum. Conclusion : These results suggest that ES may inhibit the production of IL-4, IL-13, IgE and infiltration of inflammatory cell and be beneficial oriental medicine for allergic asthma.

• Journal of Nutrition and Health
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• v.36 no.4
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• pp.368-375
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• 2003

Cancer cachexia, characterized by weight loss and progressive tissue wasting, has been postulated to be mediated by cytokines. This study was conducted to evaluate the effect of Korean Traditional Medicine (KTM ; mokhyang, jisil, osooyu) mixture on food intake, blood cytokines level and blood nutrients status of the cachexia induced-mice. Thirty male Balb/c mice aged 6-8 weets were blocked into 3 groups that were Normal (no colon26 cells) Control (colon 26 cells) and KTM (colon26 cells + KTM extract mixture) group. In Control and KTM groups, murine adenocarcinoma colon 26 cells were injected subcutaneously to induce cachexia. KTM mice were given 200 ul KTM extract mixture (7%) per day. Half of each groups were sacrificed at the 14 th day to see serum cytokines & nutrients and the others were fed until almost of control group died to see life span. food intake and body weight were decreased significantly in cachexia induced groups. Tumor weight of KTM group was significantly lower than control group. Serum cytokines (IL-1$\beta$ and TNF-$\alpha$) level of cachexia induced groups were increased than those of normal group, and those of KTM group were significantly lower than the level of control group. Total serum protein and serum albumin were higher in KTM group than other groups. TG and fatty acid were lower in cachexia induced groups than normal group. HDL-cholesterol in serum was increased in KTM group. Effect of oral administration of KTM extract mixture on survival time of colon26 bearing mice showed extension of the life span. Overall, this study showed that KTM (mokhyang, jisil, osooyu) extract mixture inhibited the growth of cancer cell, changed the secretion of cytokines induced by colon26 adenocarcinoma in mice, and changed nutrition metabolism.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.9
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• pp.1027-1034
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• 2017

The immune system is a complex process within the body that protects against disease. Recently, many studies have attempted to discover immunomodulative compounds from natural sources. Pinus koraiensis (PK) cone shell is a by-product of PK. One of the major compounds of PK cone shell is dehydroabietic acid, which has bioactivity, including antiulcer and anti-inflammatory activities. Therefore, this study was performed to examine the immunomodulative effects of PK cone shell. The immunomodulatory effects of PK cone shell extracted with 20% ethanol (EtOH) in vivo were examined initially by measuring the natural killer (NK) cell activity, phagocytic activity, Th1/Th2 cytokines release, serum immunoglobulin, and T/B cell proliferation. The NK cell activity and phagocytic activity were increased significantly by a treatment with a 20% EtOH extract of PK cone shell. Th1 type cytokine and T cell proliferation increased and Th2 type cytokine, B cell proliferation and serum immunoglobulin A, G, and E decreased after a treatment with PK cone shell extract. The 20% EtOH extract of the PK cone shell normalized the unbalanced production of Th1/Th2 type cytokine. This suggests that a 20% EtOH extract of PK cone shell has great potential as a health food.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.126-133
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• 2011

The fruit of Actinidia arguta (AA) has been used mainly for the treatment of skin diseases, diuresis, diabetes mellitus and osteoporosis in Korean traditional medicine. It is known that AA (hardy kiwi) fruit extract has an effect on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Mode of action for it is associated with the modulation of biphasic Th1/Th2 cytokines. Furthermore, DA9102 containing AA is a herbal medicine currently under phase II clinical trial for atopic dermatitis in Korea. However, no active principles of AA on the decrease of Th2 cytokines including IL-4 and IL-10 have been identified. In this study, bioactivity-guided fractionation of an alcohol extract from the dried fruits of AA using ELISA assay for IL-4 production led to the isolation of $\alpha$-linolenic acid (I), linoleic acid (II), ethyl linolenate (III), ethyl linoleate (IV) and ethyl stearate (V) as the major active components. These compounds showed the down-regulatory effects of IL-4 production in A23187-stimulated RBL-2H3 cells without cytotoxicity.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.90-98
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• 1998

Background : The CD4+ T-helper cells comprise functionally distinct subsets of Th1 and Th2 cells that are distinguished on the basis of differential cytokines production Th1 cells secrete interferon-$\gamma$, lymphotoxin, interleukin-2. Th2 cells produce interleukin-4, interleukin-5, interleukin-10. A previous study shown that Th2 cells and their cytokines increased in patients with atopic asthma. We compared cytokines(IL-4, IFN-$\gamma$) activity and subpopulation of T-lymphocytes in peripheral blood from atopic asthmatics versus non-asthmatics. Method: Fifteen patients with atopic asthma(nine men, six women), twelve patients with chronic bronchitis(six men, six women), five healthy persons(three men, two women) were studied. Activity of IL-4, IFN-$\gamma$ and T-cell subpopulation in peripheral blood were estimated. Results: Patients had a median age of 55yr. The mean activity of IL-4 of asthmatics was significantly increased(control $0.75{\pm}1.1pmol/L$, atopic asthmatics $3.50{\pm}0.75pmol/L$, chronic bronchitis $2.01{\pm}1.2pmol/L$), but IFN-$\gamma$ was not significantly increased. In the T lymphocyte sunsets the percent of CD62L+ T-lymphoeytes of asthmatics was not significantly increased (control $16.7{\pm}16.4%$, atopic asthmatics $24.8{\pm}23.6%$, chronic bronchitis $17.0{\pm}16.9%$). Conclusion: In this study elevated production of IL-4 was observed in atopic asthmatics. CD62L+T-lymphoeytes was not increased in atopic asthma.