Topical Application of Herbal Mixture Extract Inhibits Ovalbumin- or 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis

KM110329 is four traditional herbal medicine mixtures with anti-inflammatory properties. Atopic dermatitis (AD) is an inflammatory skin disease associated with enhanced T-helper2 (Th2) lymphocyte response to allergens that results in elevated serum eosinophil and Immunoglobulin E (IgE) levels and leukocyte infiltration in atopic skin sites. In this study, we investigated the effect of topical application of KM110329 ethanol extract on the ovalbumin (OVA) or 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of KM110329 on blood eosinophils, skin mast cells, production of serum IgE, and expression of cytokine mRNA in the atopic dermatitis skin lesions of OVA allergen- or DNCB-treated BALB/c mice. KM110329 significantly reduced blood eosinophils cell numbers in OVA or DNCB-treated BALB/c mice. Histological analyses demonstrated decreased mast cell count as well as dermal infiltration by inflammatory cells. In the skin lesions, mRNA expression of interleukine (IL)-4, IL-13, and IL-17 was inhibited by KM110329. KM110329 also suppressed the production of serum IgE level in both the OVA- and DNCB-induced atopic dermatitis model. Taken together, our results showed that topical application of KM110329 extracts exerts beneficial effects in AD symptoms, suggesting that KM110329 might be a useful candidate for the treatment of AD.

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Topical Application ofChrysanthemum indicum L.Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-γ, and IL-4 in Nc/Nga Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/821967 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Sunmin Park ◽

Jung Bok Lee ◽

Suna Kang

Keyword(s):

Atopic Dermatitis ◽

Topical Application ◽

Immunoglobulin E ◽

Clinical Symptoms ◽

Secondary Infection ◽

Skin Lesions ◽

Mrna Levels ◽

Dorsal Skin ◽

Gene Expressions ◽

Serum Ige

Chrysanthemum indicum L. (CIL) is widely used as an anti-inflammatory agent in Asia and our preliminary study revealed that CIL reduced interleukin (IL)-4 and IL-13 in 2,4-dinitrochlorobenzene (DNCB)-treated HaCaT cells, a human keratinocyte cell line. We investigated the atopic dermatitis (AD) effect of topically applied CIL in mice with AD-like symptoms. After topical application of 1,3-butylen glycol (control), CIL-Low (5%), CIL-High (30%), or 0.1% hydrocortisone (HC) on the AD-like skin lesions in DNCB-treated NC/Nga mice for 5 weeks, the ear thickness, mast cell infiltration, and serum immunoglobulin E (IgE), IgG1, IL-4 and interferon (IFN)-γwere measured. The gene expressions of IL-4, IL-13, and IFN-γin the dorsal skin were assayed. CIL treatment dosedependently reduced severity of clinical symptoms of dorsal skin, ear thickness, and the number of mast cells and eosinophils. CIL-High significantly decreased serum IgE, IgG1, IL-4, and IFN-γlevels and reduced mRNA levels of IFN-γ, IL-4, and IL-13 in dorsal skin lesion. The improvement by CIL-High was similar to HC, but without its adverse effects such as skin atrophy maceration, and secondary infection. In conclusion, CIL may be an effective alternative substance for the management of AD.

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Combretum quadrangulare Extract Attenuates Atopic Dermatitis-Like Skin Lesions through Modulation of MAPK Signaling in BALB/c Mice

Molecules ◽

10.3390/molecules25082003 ◽

2020 ◽

Vol 25 (8) ◽

pp. 2003 ◽

Cited By ~ 1

Author(s):

Ju-Hyoung Park ◽

Min Hee Hwang ◽

Young-Rak Cho ◽

Seong Su Hong ◽

Jae-Shin Kang ◽

...

Keyword(s):

Atopic Dermatitis ◽

Immunoglobulin E ◽

Ethanol Extract ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Mapk Signaling ◽

Chronic Inflammatory Disease ◽

Mitogen Activated Protein Kinase ◽

Mrna Levels ◽

Cytokines And Chemokines

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

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Metabolomics Distinguishes DOCK8 Deficiency from Atopic Dermatitis: Towards a Biomarker Discovery

Metabolites ◽

10.3390/metabo9110274 ◽

2019 ◽

Vol 9 (11) ◽

pp. 274 ◽

Cited By ~ 4

Author(s):

Minnie Jacob ◽

Xinyun Gu ◽

Xian Luo ◽

Hamoud Al-Mousa ◽

Rand Arnaout ◽

...

Keyword(s):

Atopic Dermatitis ◽

Biomarker Discovery ◽

Isotope Labeling ◽

Immunoglobulin E ◽

Clinical Symptoms ◽

Elevated Serum ◽

Severe Atopic Dermatitis ◽

Serum Ige ◽

Tryptophan Degradation ◽

Dock8 Deficiency

Bi-allelic mutations in the dedicator of cytokinesis 8 (DOCK8) are responsible for a rare autosomal recessive primary combined immunodeficiency syndrome, characterized by atopic dermatitis, elevated serum Immunoglobulin E (IgE) levels, recurrent severe cutaneous viral infections, autoimmunity, and predisposition to malignancy. The molecular link between DOCK8 deficiency and atopic skin inflammation remains unknown. Severe atopic dermatitis (AD) and DOCK8 deficiency share some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. Increased serum IgE levels are characteristic of, but not specific to allergic diseases. Herein, we aimed to study the metabolomic profiles of DOCK8-deficient and AD patients for potential disease-specific biomarkers using chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Serum samples were collected from DOCK8-deficient (n = 10) and AD (n = 9) patients. Metabolomics profiling using CIL LC-MS was performed on patient samples and compared to unrelated healthy controls (n = 33). Seven metabolites were positively identified, distinguishing DOCK8-deficient from AD patients. Aspartic acid and 3-hydroxyanthranillic acid (3HAA, a tryptophan degradation pathway intermediate) were up-regulated in DOCK8 deficiency, whereas hypotaurine, leucyl-phenylalanine, glycyl-phenylalanine, and guanosine were down-regulated. Hypotaurine, 3-hydroxyanthranillic acid, and glycyl-phenylalanine were identified as potential biomarkers specific to DOCK8 deficiency. Aspartate availability has been recently implicated as a limiting metabolite for tumour growth and 3HAA; furthermore, other tryptophan metabolism pathway-related molecules have been considered as potential novel targets for cancer therapy. Taken together, perturbations in tryptophan degradation and increased availability of aspartate suggest a link of DOCK8 deficiency to oncogenesis. Additionally, perturbations in taurine and dipeptides metabolism suggest altered antixidation and cell signaling states in DOCK8 deficiency. Further studies examining the mechanisms underlying these observations are necessary.

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Oral Administration of Herbal Mixture Extract Inhibits 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in BALB/c Mice

Mediators of Inflammation ◽

10.1155/2014/319438 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Soon Re Kim ◽

Han-Seok Choi ◽

Hye Sook Seo ◽

Jin Mo Ku ◽

Se Hyang Hong ◽

...

Keyword(s):

Mast Cells ◽

Oral Administration ◽

Inflammatory Cell ◽

Ethanol Extract ◽

Inflammatory Cells ◽

Skin Lesions ◽

Cell Infiltration ◽

Mrna Levels ◽

Beneficial Effects ◽

Th2 Cytokine

CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL-) 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1). In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD.

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Kampo Medicines for Mite Antigen-Induced Allergic Dermatitis in NC/Nga Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neh077 ◽

2005 ◽

Vol 2 (2) ◽

pp. 191-199 ◽

Cited By ~ 53

Author(s):

Xiu Kun Gao ◽

Kazutoshi Fuseda ◽

Tomonori Shibata ◽

Hiroyuki Tanaka ◽

Naoki Inagaki ◽

...

Keyword(s):

Atopic Dermatitis ◽

Mrna Expression ◽

Elevated Serum ◽

Inflammatory Cells ◽

Interferon Γ ◽

Interleukin 4 ◽

Tape Stripping ◽

Cervical Lymph Nodes ◽

Serum Ige ◽

Allergic Dermatitis

We have established an allergic dermatitis model in NC/Nga mice by repeated local exposure of mite antigen for analyzing atopic dermatitis. We examined how four Kampo medicines, Juzen-taiho-to, Hochu-ekki-to, Shofu-san and Oren-gedoku-to, on the dermatitis model to obtain basic information on their usefulness for treating atopic dermatitis. Mite antigen (Dermatophagoides farinaecrude extract) solution at a concentration of 10 mg/ml was painted on the ear of NC/Nga mice after tape stripping. The procedure was repeated five times, at 7 day intervals. An apparent biphasic ear swelling was caused after the fourth and fifth antigen exposures with elevated serum IgE levels and accumulation of inflammatory cells. In the cervical lymph nodes and ear lobes, the five procedures of antigen exposure induced interleukin-4 mRNA expression but reduced interferon-γ mRNA expression. Oral administration of all four Kampo medicines inhibited the formation of ear swelling and inflammatory cell accumulation. Juzen-taiho-to and Hochu-ekki-to apparently prevented the elevation of serum IgE level. Furthermore, the four Kampo medicines showed a tendency to prevent not only the increase in interleukin-4 mRNA expression but also the decrease in interferon-γ mRNA expression. The present results indicate that Juzen-taiho-to, Hochu-ekki-to, Shofu-san and Oren-gedoku-to may correct the Th1/Th2 balance skewed to Th2, and this activity helps inhibit dermatitis in NC/Nga mice. The ability of the Kampo medicines to correct the Th1/Th2 balance seems to underlie their effectiveness in treating of atopic dermatitis.

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Effects of mineral complex material treatment on 2,4- dinitrochlorobenzene-induced atopic dermatitis like-skin lesions in mice model

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03259-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Johny Bajgai ◽

Jing Xingyu ◽

Ailyn Fadriquela ◽

Rahima Begum ◽

Dong Heui Kim ◽

...

Keyword(s):

Atopic Dermatitis ◽

Water Loss ◽

Immunoglobulin E ◽

Skin Barrier ◽

Skin Lesions ◽

Total Serum ◽

Skin Barrier Function ◽

Barrier Dysfunction ◽

Complex Material ◽

Mineral Complex

Abstract Background Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. Methods Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. Results Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. Conclusion Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

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Topical Application of Eupatilin Ameliorates Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

Annals of Dermatology ◽

10.5021/ad.2017.29.1.61 ◽

2017 ◽

Vol 29 (1) ◽

pp. 61 ◽

Cited By ~ 7

Author(s):

Ji Hyun Lee ◽

Ye Jin Lee ◽

Jun Young Lee ◽

Young Min Park

Keyword(s):

Atopic Dermatitis ◽

Topical Application ◽

Skin Lesions

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Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality

Nutrients ◽

10.3390/nu12123638 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3638

Author(s):

Yoon-Young Sung ◽

Heung-Joo Yuk ◽

Won-Kyung Yang ◽

Seung-Hyung Kim ◽

Dong-Seon Kim

Keyword(s):

Atopic Dermatitis ◽

Immunoglobulin E ◽

Allergic Inflammation ◽

Skin Barrier ◽

Human Keratinocytes ◽

Skin Lesions ◽

Protein Levels ◽

Siraitia Grosvenorii ◽

Ifn Γ

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

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Fermented Morinda citrifolia (Noni) Alleviates DNCB-Induced Atopic Dermatitis in NC/Nga Mice through Modulating Immune Balance and Skin Barrier Function

Nutrients ◽

10.3390/nu12010249 ◽

2020 ◽

Vol 12 (1) ◽

pp. 249 ◽

Cited By ~ 1

Author(s):

Kim ◽

Seong ◽

Choung

Keyword(s):

Atopic Dermatitis ◽

Barrier Function ◽

Molecular Mechanisms ◽

Inflammatory Diseases ◽

Skin Barrier ◽

Inflammatory Cells ◽

Skin Lesions ◽

Morinda Citrifolia ◽

Skin Barrier Function ◽

Immune Balance

Morinda citrifolia, a fruit generally known as “Noni”, has been traditionally used in parts of East Asia to relieve inflammatory diseases. Although several studies using noni have been reported, the effect of fermented Morinda citrifolia (F.NONI) on atopic dermatitis (AD) has not been investigated. Thus, we aimed to investigate the improving effect of F.NONI treatment on AD-like skin lesions and elucidate molecular mechanisms. F.NONI was prepared by the fermentation of noni fruit with probiotics and then extracted. F.NONI was orally administrated to NC/Nga mice to evaluate its therapeutic effect on 2,4-dinitrochlorobenzene (DNCB)-induced AD. Oral administration of F.NONI significantly alleviated AD lesions and symptoms such as dermatitis scores, ear thickness, scratching behavior, epidermal thickness, and infiltration of inflammatory cells (e.g., mast cells and eosinophils). In addition, F.NONI treatment reduced the levels of histamine, IgE and IgG1/IgG2a ratio, thymus and activation regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP) in serum and beneficially modulated the expressions of Th1, Th2, Th17, and Th22-mediated cytokines in lesioned skin and splenocytes. Furthermore, the expressions of the skin barrier-related proteins including filaggrin (FLG), loricrin (LOR), involucrin (IVL), zonula occludens-1 (ZO-1), and occludin (OCC) were restored by F.NONI treatment. Taken together, these results suggest that F.NONI could be a therapeutic agent to attenuate AD-like skin lesions through modulating the immune balance and skin barrier function.

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