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Nutrients Feb 2020Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by immune dysregulation. This study explored the anti-inflammatory and immunomodulatory...
Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by immune dysregulation. This study explored the anti-inflammatory and immunomodulatory effects of the ethanol extract (CA) on an AD-like dermal disorder. Treatment with CA inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner in inflammatory stimulated HaCaT cells by interferon-γ (IFN-γ) and TNF-α-triggered inflammation. Eight-week-old BALB/c mice treated with 2,4-dinitrochlorobenzene (DNCB) were used as a mouse model of AD. In AD induce model, we had two types treatment of CA; skin local administration (80 µg/cm, AD+CA-80) and oral administration (200 mg/kg/d, AD+CA-200). Interestingly, the CA-treated groups exhibited considerably decreased mast cell infiltration in the ear tissue. In addition, the expression of IL-6 in mast cells, as well as the expression of various pathogenic cytokines, such as TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, iNOS, COX-2, and CXCL9, was reduced in both AD+CA-80 and AD+CA-200 groups. Collectively, our data demonstrate the pharmacological role and signaling mechanism of CA in the regulation of allergic inflammation of the skin, which supports our hypothesis that CA could potentially be developed as a therapeutic agent for AD.
Topics: Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents; Centella; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Immunomodulation; Inflammation; Mast Cells; Mice; Mice, Inbred BALB C; Plant Extracts; Skin; Triterpenes
PubMed: 32033291
DOI: 10.3390/nu12020411 -
International Journal of Molecular... Jul 2021Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem....
Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.
Topics: Animals; Anti-Inflammatory Agents; Benzylisoquinolines; Dermatitis, Atopic; Dinitrochlorobenzene; HaCaT Cells; Humans; Interferon-gamma; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; NF-kappa B; Tumor Necrosis Factor-alpha
PubMed: 34361003
DOI: 10.3390/ijms22158237 -
International Journal of Molecular... Aug 2023In dermatological research, 2,4-dinitrochlorbenzene (DNCB)-induced atopic dermatitis (AD) is a standard model as it displays many disease-associated characteristics of...
In dermatological research, 2,4-dinitrochlorbenzene (DNCB)-induced atopic dermatitis (AD) is a standard model as it displays many disease-associated characteristics of human AD. However, the reproducibility of the model is challenging due to the lack of information regarding the methodology and the description of the phenotype and endotype of the mimicked disease. In this study, a DNCB-induced mouse model was established with a detailed procedure description and classification of the AD human-like skin type. The disease was induced with 1% DNCB in the sensitization phase and repeated applications of 0.3% and 0.5% DNCB in the challenging phase which led to a mild phenotype of AD eczema. Pathophysiological changes of the dorsal skin were measured: thickening of the epidermis and dermis, altered skin barrier proteins, increased TH1 and TH2 cytokine expression, a shift in polyunsaturated fatty acids, increased pro-resolving and inflammatory mediator formation, and dysregulated inflammation-associated gene expression. A link to type I allergy reactions was evaluated by increased mast cell infiltration into the skin accompanied by elevated IgE and histamine levels in plasma. As expected for mild AD, no systemic inflammation was observed. In conclusion, this experimental setup demonstrates many features of a mild human-like extrinsic AD in murine skin.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Reproducibility of Results; Immunoglobulin E; Skin; Cytokines; Inflammation; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37569701
DOI: 10.3390/ijms241512325 -
Nutrients Jan 2020, 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...
, 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 (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.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Fermentation; Filaggrin Proteins; Fruit; Histamine; Immunoglobulin G; Intermediate Filament Proteins; Membrane Proteins; Mice; Morinda; Occludin; Plant Extracts; Protein Precursors; Pruritus; Skin; T-Lymphocytes, Helper-Inducer; Zonula Occludens-1 Protein
PubMed: 31963703
DOI: 10.3390/nu12010249 -
Iranian Journal of Pharmaceutical... Dec 2022Irritant contact dermatitis is a common inflammatory skin disease characterized by skin barrier dysfunction, eczematous dermatitis, and chronic itching. This disease...
BACKGROUND
Irritant contact dermatitis is a common inflammatory skin disease characterized by skin barrier dysfunction, eczematous dermatitis, and chronic itching. This disease severely affects the quality of life. Considering that the current treatment approaches are not ideal, more extensive research is needed to develop new treatments. Mainly, a mouse model is needed to investigate the effectiveness of new drugs to treat this disease.
OBJECTIVES
This study was conducted to create a mouse model of irritant contact dermatitis.
METHODS
In the current study, we used BALB/c female mice to prepare a mouse model of irritant contact dermatitis. To induce irritant contact dermatitis, we used a dinitrochlorobenzene mixture with acetone/olive oil as an irritant. After 10 days of application, the mouse skin tissue was isolated and examined in terms of histopathology.
RESULTS
The introduced protocol created an irritant contact dermatitis model clinically and histopathologically.
CONCLUSIONS
In the present study, we introduced a new protocol using a mixture of dinitrochlorobenzene and acetone/olive oil to create an irritant contact dermatitis model. Mouse models have been extensively used to discover the complex mechanisms of irritant contact dermatitis and provide a preclinical platform before conducting clinical interventional research on humans to evaluate a new therapeutic approach. However, one should always look for models that cause the least pain and suffering in the animal and simultaneously are simple and reliable for the desired studies. Thus, our protocol is a new approach that can be effective and painless in creating a model of irritant contact dermatitis.
PubMed: 36710994
DOI: 10.5812/ijpr-130881 -
Biomedicine & Pharmacotherapy =... Sep 2020Psoralea corylifolia is a medicinal herb that provides advantageous pharmacological effects against vitiligo and skin rash. Former studies have shown that bakuchicin, a...
Psoralea corylifolia is a medicinal herb that provides advantageous pharmacological effects against vitiligo and skin rash. Former studies have shown that bakuchicin, a furanocoumarin compound from the fruits of P. corylifolia, has therapeutic effects against inflammation, and infection. This study aimed to define the pharmacological effects of bakuchicin on inflammatory responses and lichenification, the major symptoms of atopic dermatitis (AD). To induce AD-like skin inflammation, we exposed the ears of female BALB/c mice to 2, 4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae (house dust mite) extract (DFE) for 4 weeks. Intragastric administration of bakuchicin attenuated the symptoms of AD-like skin inflammation, as evident by reductions in ear thickness, erythema, and keratosis. Bakuchicin also reversed increases in auricular epidermal and dermal layer thicknesses, and attenuated eosinophil and mast cell infiltration in AD-induced mice. It also suppressed T2 gene expression as well as that of pro-inflammatory cytokines and chemokines, such as interleukin (IL)-4, IL-13, IL-31, IL-1β, IL-6, CXCL-1, and CCL-17 in the ear tissue. The levels of total and DFE-specific immunoglobulin (Ig)E, and IgG2a in the mice sera were reduced by the bakuchicin. To investigate the effect of bakuchicin on keratinocytes, experiments were performed using HaCaT cells, the representative cell type used in skin disease studies. Tumor necrosis factor-α and interferon-γ were used to activate keratinocytes. Bakuchicin suppressed T2 gene expression and that of pro-inflammatory cytokines and chemokines; it also suppressed STAT-1 phosphorylation and the nuclear translocation of NF-κB in activated keratinocytes. These results suggest that bakuchicin attenuated AD symptoms, thus suggesting it as a potential therapeutic agent for the treatment of AD.
Topics: Animals; Anti-Inflammatory Agents; Antigens, Dermatophagoides; Arthropod Proteins; Cell Line; Chronic Disease; Cytokines; Dermatitis, Atopic; Dermatologic Agents; Dinitrochlorobenzene; Disease Models, Animal; Female; Heterocyclic Compounds, 3-Ring; Humans; Immunoglobulin E; Immunoglobulin G; Keratinocytes; Mice, Inbred BALB C; NF-kappa B; Phosphorylation; STAT1 Transcription Factor; Skin
PubMed: 32768955
DOI: 10.1016/j.biopha.2020.110466 -
Phytomedicine : International Journal... Jul 2023Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune...
Anti-inflammatory effect and metabolic mechanism of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on atopic dermatitis in vivo and in vitro.
BACKGROUND
Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune response. AD treatment include glucocorticoids and immunosuppressants. However, long-term treatment can have serious side effects. Thus, an effective AD treatment with fewer side effects is required. Natural materials, including herbal medicines, have potential applications.
PURPOSE
This study evaluated the in vivo and in vitro therapeutic effects of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on AD and investigated the underlying metabolic mechanisms.
METHODS
The anti-inflammatory effects of BS012 were assessed using a mouse model of AD induced by 1‑chloro-2,4-dinitrobenzene (DNCB) and in tumor necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ) stimulated normal human epidermal keratinocytes (NHEKs). In DNCB-induced mice, total dermatitis score, histopathological analysis, and immune cell factors were assessed to evaluate the anti-atopic activity. In TNF-α/IFN-γ-stimulated NHEKs, pro-inflammatory cytokines, chemokines, and related signaling pathways were investigated. Serum and intracellular metabolomics were performed to identify the metabolic mechanism underlying the therapeutic effects of BS012 treatment.
RESULTS
In DNCB-induced mice, BS012 showed potent anti-atopic activity, including reducing AD-like skin lesions and inhibiting the expression of Th2 cytokines and thymic stromal lymphopoietin. In TNF-α/IFN-γ-stimulated keratinocytes, BS012 dose-dependently inhibited the expression of pro-inflammatory cytokines and chemokines by blocking nuclear factor-kappa B and signal transducer and activator of transcription signaling pathways. Serum metabolic profiles of mice revealed significant changes in lipid metabolism related to inflammation in AD. Intracellular metabolome analysis revealed that BS012 treatment affected the metabolism associated with inflammation, skin barrier function, and lipid organization of the stratum corneum.
CONCLUSION
BS012 exerts anti-atopic activity by reducing the Th2-specific inflammatory response and improving skin barrier function in AD in vivo and in vitro. These effects are mainly related to the inhibition of inflammation and recovery of metabolic imbalance in lipid organization. BS012, a novel combination with strong activity in suppressing the Th2-immune response, could be a potential alternative for AD treatment. Furthermore, the metabolic mechanism in vivo and in vitro using a metabolomics approach will provide crucial information for the development of natural products for AD treatment.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Platycodon; Asarum; Cinnamomum aromaticum; Tumor Necrosis Factor-alpha; Dinitrochlorobenzene; Anti-Inflammatory Agents; Cytokines; Inflammation; Chemokines; Interferon-gamma; Dinitrobenzenes; Lipids; Skin; Mice, Inbred BALB C
PubMed: 37187105
DOI: 10.1016/j.phymed.2023.154818 -
Biomedicine & Pharmacotherapy =... Dec 2023The purpose of this study was to investigate the mechanism through which rosemary essential oil treats atopic dermatitis.
OBJECTIVE
The purpose of this study was to investigate the mechanism through which rosemary essential oil treats atopic dermatitis.
METHODS
A dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model was established and treated with low (1%), medium (2%), and high (4%) doses of Rosmarinus officinalis essential oil (EORO). Serum levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in each group were determined using enzyme-linked immunosorbent assay (ELISA). Skin tissues were stained with hematoxylin-eosin and toluidine blue. We used network pharmacology and molecular docking techniques to verify the biological activity of essential proteins and their corresponding compounds in the pathway. Gas chromatography-mass spectrometry (GC-MS) was used for metabolomics analysis and multivariate statistical analysis of mouse serum to screen differential metabolites and metabolic pathway analysis. Protein expression of p-JAK1, CD4+ cells, and IL-4 in the skin tissue was detected by immunohistochemistry analysis. Protein levels of STAT3, p-STAT3, P65, and p-P65 in damaged skin tissues were detected using western blotting.
RESULT
The skin of mice in the model group showed different degrees of erythema, dryness, scratches, epidermal erosion and shedding, and crusting. After treatment, the serum levels of IL-6 and TNF-α in EORO group were significantly decreased, and the expression of p-JAK1,CD4 + cells, IL-4, p-P65 / P65 and p-STAT3 / STAT3 proteins in skin tissues were decreased.
CONCLUSION
EORO can effectively improve DNCB-induced AD-like skin lesions in mice by regulating the JAK/STAT/NF-κB signaling pathway, thereby reducing the production of downstream arachidonic acid metabolites, inhibiting skin inflammation, and restoring epidermal barrier function.
Topics: Animals; Mice; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Interleukin-4; Interleukin-6; Mice, Inbred BALB C; Molecular Docking Simulation; NF-kappa B; Oils, Volatile; Rosmarinus; Signal Transduction; Skin; Tumor Necrosis Factor-alpha
PubMed: 37879216
DOI: 10.1016/j.biopha.2023.115727 -
Dermatology and Therapy Nov 2022For decades, contact immunotherapy with dinitrochlorobenzene, diphencyprone, and squaric acid dibutylester has played an important role in both clinical practice and... (Review)
Review
For decades, contact immunotherapy with dinitrochlorobenzene, diphencyprone, and squaric acid dibutylester has played an important role in both clinical practice and scientific research. It is listed as the first-line treatment for extensive alopecia areata and was more recently approved for melanoma treatment as an orphan drug in the USA. Moreover, owing to the relative low cost and safety, topical immunotherapy has also been used in many infectious, neoplastic, and inflammatory dermatological diseases. It is especially valuable in vulnerable groups, for cosmetic/pain sensitive areas, or for multiple lesions. In this review, we summarize the current evidence supporting the use of contact immunotherapy for treatment of skin diseases, from articles collected from PubMed database. Owing to space limitation and already numerous studies focusing on alopecia areata, we include only skin diseases other than alopecia areata. In addition to diseases that have been reported to be treated by contact immunotherapy, the hypothesized mechanism, prognosis prediction, efficacy, and safety of these topical agents are discussed.
PubMed: 36136235
DOI: 10.1007/s13555-022-00818-7 -
Frontiers in Immunology 2023Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome...
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome abnormalities and type-2-skewed immune dysregulation. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays critical roles in various biological processes. However, the role of STAT3 in epidermal keratinocytes in AD remains unclear. In this study, we generated an epidermal keratinocyte-specific -deficient mouse strain (termed cKO mice). After topical 2,4-dinitrochlorobenzene (DNCB) treatment, cKO mice developed worsened AD-like skin inflammation with increased Ki67 cells, decreased filaggrin and loricrin expression, and downregulated S100A9 and LL37. The dominant microbial population in cKO mice changed from to . DNCB-treated cKO mice displayed more infiltrating type-2 inflammatory cells, including mast cells, eosinophils, and CD4T cells, accompanied by increased skin IL-4 and serum IgE levels. Moreover, thymic stromal lymphopoietin (TSLP), mainly produced by keratinocytes, was highly expressed in the ear skin of cKO mice and chemoattracted more TSLPR cells. TSLP blockade significantly alleviated DNCB-induced AD-like skin inflammation in cKO mice. Thus, epidermal keratinocyte-specific STAT3 deficiency can aggravate AD-like skin inflammation in mice, possibly through TSLP dysregulation.
Topics: Animals; Mice; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Inflammation; Keratinocytes; STAT3 Transcription Factor; Thymic Stromal Lymphopoietin; Up-Regulation
PubMed: 38053996
DOI: 10.3389/fimmu.2023.1273182