• Toxicological Research
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• v.27 no.3
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• pp.173-180
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• 2011

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin, has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore, we investigated the effect of EtOH extract of premature C. unshiu on AD. We did this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory effect for premature C. unshiu on the expression of inflammatory chemokines in IFN-${\gamma}$ and TNF-${\alpha}$ stimulated HaCaT human keratinocytes. We found that extract of premature C. unshiu reduced DNCB-induced symptoms such as hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD-like animal model. The extract decreased levels of IFN-${\gamma}$ and IL-4 in ConA-stimulated splenocytes isolated from DNCB-treated mice. Also, extract of premature C. unshiu inhibited mRNA expression and protein production of TARC and MDC through the inhibition of STAT1 phosphorylation. These results suggest that C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as TARC and MDC.

• Korean Journal of Food Science and Technology
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• v.40 no.1
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• pp.82-87
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• 2008

Atopic dermatitis (AD) is characterized by chronic relapsing inflammation and is associated with hyper-production of immunoglobulin E (IgE). Recent studies have suggested that one of the treatments to alleviate symptoms of AD could be a supplementation of probiotics, Lactobacillus, Rhamnosus, Bifidus, etc. The purpose of this study was to evaluate the effects of probiotics on immune parameters in NC/Nga mice treated with 1-chloro-2,4-dinitro-benzene (DNCB). To induce atopic dermatitis, DNCB was treated to the back of mice for 2 weeks. Then, NC/Nga mice were divided into the four experimental groups randomly. Probiotics fragment, probiotics with other complex (Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12LbL, L. plantarum K8, L. plantarum K8 fragment, ${\gamma}$-linolenic acid), antihistamine, and distilled water were administrated orally to the NC/Nga mouse for 4 weeks of experimental period. The groups were probiotics fragment group (DPF), probiotics with other complex group (DPOC), antihistamine group (DAH) and distilled water group (DDW) as a control group. The levels of serum IgE, interlukin-4 (IL-4), interlukin-5 (IL-5), interferon-gamma (IFN-${\gamma}$) and spleenocyte IgE were measured. The levels of serum IgE were significantly different among the four experimental groups. Before the treatment, there was no differences among the groups. However, from the first through the third week of the treatments, the levels of serum IgE in the probiotics (DPF, DPOC) and antihistamine (DAH) groups were lower than those of control group (p < 0.05). The levels of serum IL-4 of DPOC group was significantly lower than that of control group (p < 0.05) and serum IL-5 levels of DPF, DPOC, and DAH groups were significantly lower than that of control group. The levels of serum IFN-${\gamma}$ were not different among the four experimental groups. The levels of serum IgE in supernatant of spleen lymphocytes were not significantly different among the groups. These results suggest that probiotics supplementation showed partial effectiveness in the DNCB treated NC/Nga mice via modulation of IgE level and IL-4, IL-5 production. Based on these findings, probiotics exhibited the inhibitory effect via IL-4 production thereby inhibited the production of IgE in atopic animal model NC/Nga mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1099-1107
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• 2007

This study was investigated the anti-allergic effect of SJSBT on DNCB induced atopic dermatitis in NC/Nga mice. We summerized as the follow. SJSBT significantly decreased the clinical manifestations of atopic dermatitis including itching, dryness, edema, hemorrhage, and lichenification in dose dependent manner. SJSBT markedly suppressed invasion and edema of leukocytes and mast cell in dorsal skin and ear tissue. SJSBT significantly reduced the number of CD11b+/Gr-1 cell compared with positive control, but it had no affect the number of CD3+ and CCR3+/CD3+ cell. SJSBT markedly suppressed the expression of cytokine and chemokine such as IL-6, $TNF-{\alpha}$, eotaxin and CCR3 compared with positive control group. SJSBT significantly decreased the invasion of CD4+ and CCR3+ cell in ear and dorsal skin tissue compared with positive control group by using immunohistochemical staining. Taken together, these findings suggested that SJSBT has an anti-allergic activity and this might be useful for the clinical application to treat allergic diseases such as atopic dermatitis.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.634-640
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• 2017

Atopic dermatitis (AD) is a common inflammatory skin disorder mediated by inflammatory cells, such as macrophages and mast cells. Rifampicin is mainly used for the treatment of tuberculosis. Recently, it was reported that rifampicin has anti-inflammatory and immune-suppressive activities. In this study, we investigated the effect of rifampicin on atopic dermatitis in vivo and in vitro. AD was induced by treatment with 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. A subset of mice was then treated with rifampicin by oral administration. The severity score and scratching behavior were alleviated in the rifampicin-treated group. Serum immunoglobulin E (IgE) and interleukin-4 (IL-4) levels were also ameliorated in mice treated with rifampicin. We next examined whether rifampicin has anti-atopic activity via suppression of mast cell activation. Rifampicin suppressed the release of ${\beta}$-hexosaminidase and histamine from human mast cell (HMC)-1 cultures stimulated with compound 48/80. Treatment with rifampicin also inhibited secretion of inflammatory mediators, such tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) and prostaglandin $D_2$ ($PGD_2$), in mast cells activated by compound 48/80. The mRNA expression of cyclooxygenase 2 (COX-2) was reduced in the cells treated with rifampicin in a concentration-dependent manner. These results suggest that rifampicin can be used to treat atopic dermatitis.

• 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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.1
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• pp.46-61
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• 2009

Background and Objectives : Allergic Contact Dermatitis is the disease affected by industrialization. The more industrialization advanced, the more materials that could induce the allergic contact dermatitis have been increased. Therefore in oriental medicine, various studies have been performed. The objective of this study is to investigate the effects of Naetakchunkeum-san on the Allergic Contact Dermatitis induced by 2,4-dinitro-chlorobezene(DNCB). Meterial and Methods : Twenty eight mice were divided into four groups ; normal, control, experimental group A and B. Control and experimental group were induced allergic contact dermatitis by DNCB. Experimental group A was orally administered the Naetakchunkeum-san and experimental group B was orally administered the prednisolone. In this study, ear thickness measurement, observation auricle microphotograph, Myeloperoxidase(MPO) activity measurement, Reverse transcription-polymerase chain reaction(RT-PCR) analysis of the mRNA level of $TNF-\alpha$, $IL-1\beta$, $INF-\gamma$ were performed on these four groups. In addition, the effect of Naetakchunkeum-san on cell viability and the effect of Naetakchunkeum-san on the compound 48/80-induced histamine release from HMC and RPMC were measured, Results : 1. In contact hypersensitivity assay, experimental group A and B showed decreased ear thickness compared with control group, 2. In experimental group A, pathological lesion of dermatitis were alleviated. In addition, the numbers of infiltrated cells were reduced, and cleft was not shown compared with control group, In experimental group B, similar results were shown. 3. There was a significant increase in MPO activity in control group compared with normal group, Experimental group A and B significantly inhibited the increase in MPO activity compared with control group. 4, The level of expression of $TNF-\alpha$, $IL-1\beta$, $INF-\gamma$ in experimental group A and B were significantly lower than those in control group. As the internal control, cyclophilin mRNA was also reverse-transcribed and amplified. 5, In MTT assay, there were no statistically significant differences in 100 ${\mu}g/ml$, 200 ${\mu}g/ml$, 500 ${\mu}g/ml$, 1000 ${\mu}g/ml$ Naetakchunkeum-san treated group from 0 ${\mu}g/ml$ Naetakchunkeum-san treated group as determined by the Tukey test. 6. Naetakchunkeum-san dose-dependently inhibited the compound 48/80-induced histamine release from both HMC and RPMC. Conclusions : According to above experiments, Naetakchunkeum-san may be applied to allergic contact dermatitis.

• Applied Microscopy
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• v.38 no.3
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• pp.167-174
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• 2008

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease that often has asthma and allergic rhinitis. Magnesium salts, the important component of minerals in Dead Sea water, are known to exhibit beneficial effects in inflammatory disease. Favorable effects of magnesium ions and sea water treated to the skin of patients with contact dermatitis have been reported. But histological and immunological investigations are insufficient. This study was performed to examine the inhibitory effect of magnesium-rich sea mineral water on the development of AD-like skin lesions in hairless mice. AD-like skin lesions are induced by the repeated application of 2,4-dinitrochlorobenzene (DNCB). Local application of magnesium-rich sea mineral water on hairless mice skin applied with DNCB inhibited the development of AD-like skin lesions as exemplified by a significant increase in skin hydration (p<0.01), and a decrease in epidermal water loss (p<0.01). Serum IgE level was also significantly decreased (p<0.01). These results suggest that magnesium-rich sea mineral water inhibits the development of DNCB-induced AD-like skin lesions in hairless mice. These observations indicate that magnesium-rich sea mineral water may be alternative and assistant substances for the management of AD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.5
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• pp.187-192
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• 2022

The purpose of this study is to examine the effect of herbal medicine complex (HMC) containing Camellia sinensis L., Duchoesna chrysantha, Houttuynia cordata Thunberg, Poncirus trifoliata Rafinesque on skin inflammation and atopic dermatitis. First, we examined the anti-inflammatory effect of HMC in TNF-α induced human keratinocytes (HaCaT cell). Real-time PCR and western blotting were performed to evaluate the expression of inflammatory cytokines (e.g., iNOS, COX-2, IL-6, IL-8) mRNA and protein. Four-weeks old male NC/Nga mice were treated with 1% 2,4-dinitrochlorobenzene (DNCB) solution and used as an atopic dermatitis mice model. And, HMC (200 mg/kg or 400 mg/kg) was administered directly into the stomach of mice for 4 weeks, and blood or serum analysis, tissue staining were performed after oral gavage. As a result HMC inhibited the mRNA expression of iNOS, COX-2, IL-6, and IL-8, which had been increased by TNF-α in HaCaT cells. In addition, the protein expression was also significantly suppressed in the same way as the mRNA expression results. The in vivo experiment results showed that, HMC administration reduced thickening of the epidermis and infiltration of eosinophil into the skin stratum basale compared to DNCB treatment. In addition, HMC administration significantly reduced the inflammatory cytokines (IL-4, IL-5, IL-6, and IL-13) production and immunocyte (white blood cell, lymphocyte, neutrophil, and eosinophil) count compared to DNCB treatment. Moreover, the serum IgE and histamine level was decreased by HMC administration. These results suggest that HMC can be used as effective herbal medicine extract for skin inflammation and atopic dermatitis. And this study may contribute to the development of the herbal medicine-based drug for the treatment of skin inflammation and atopic dermatitis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.3
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• pp.298-305
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• 2017

Atopic dermatitis is a chronic, relapsing inflammatory skin disease. This study aimed to investigate the therapeutic benefits of Aronia melanocarpa (AM) and Moringa oleifera seed extract (MO) on experimental atopic dermatitis. We examined the effects of AM or MO and their combination on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in BALB/c mice as well as tumor necrosis factor $(TNF)-{\alpha}$ and interferon $(IFN)-{\gamma}-stimulated$ HaCaT keratinocytes. Mice were orally treated with extract during repeated application of DNCB to shaved dorsal skin. Our results show that treatment with AM and MO in combination reduced histological manifestations such as epidermal hyperplasia and inflammatory cell infiltration. Furthermore, it significantly decreased skin thickness and serum immunoglobulin E (IgE) level compared to the AM or MO alone treated group. Combined extract of AM and MO suppressed expression of $TNF-{\alpha}/IFN-{\gamma}-induced$ T helper 2 (Th2) chemokines such as thymus and activation-regulated chemokine and macrophage-derived chemokine. To sum up, combination of AM and MO suppressed the inflammatory response and serum IgE as an indicator of several allergic diseases in DNCB-induced experimental atopic dermatitis and Th2 chemokine expression in HaCaT cells. This result suggests that combination of AM and MO could be a valuable strategy to improve atopic dermatitis.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.33 no.3
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• pp.1-26
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• 2020

Objectives : This study was to examine the effects of 3 types of BTS which were excluded talcum only or replaced talcum to Lonicera japonicae Flos or Kochiae Fructus on the DNCB-induced atopic dermatitis in mice. Methods : In this study, Balb/c mice were divided into five groups: normal, control, GBT(BTS except talcum), GBTG(GBT added Lonicera japonicae Flos), and GBTJ(GBT added Kochiae Fructus). And the effects on atopic dermatitis were evaluated by weight change, ear's thickness and weight, thickness of dorsal skin, severity scale of dorsal skin, histopathologic findings of dorsal skin by H&E and toluidine blue stain, proliferation of splenocyte and thymocyte in vitro, proliferation of splenocyte in vivo, IL-4, TNF-α, IgE in serum. Results : There were no significantly changes in body weight and effect of ear's weight in GBT, GBTG, and GBTJ group. The thickness of ear of GBT and GBTJ group showed significant decrease. And the thickness of dorsal skin of GBTJ group significantly decreased compared to the control, GBT, and GBTG group. All the treated groups significantly decreased in severity scale, histopathologically reduced epidermal thickness, and mast cell infiltration. In vitro, all the treated groups increased in the proliferation rates of splenocyte. However, in vivo study, it showed a falling tendency and GBT group significantly decreased compared to control, GBTG, and GBTJ group. In vitro study, GBTG group significantly decreased in the proliferation rates of thymocyte. There was no IgE contents chnage in GBT, GBTG, and GBTJ groups but IL-4 and TNF-α contents were significantly decreased. Conclusions : GBT, GBTG, and GBTJ are expected to improve symptoms of atopic dermatitis and further studies are needed for development of BTS's transformation.