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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 -
The Journal of Allergy and Clinical... Jun 2022Circular RNA (circRNA) has been implicated in various diseases; however, its role in atopic dermatitis (AD) or psoriasis remains unclear.
BACKGROUND
Circular RNA (circRNA) has been implicated in various diseases; however, its role in atopic dermatitis (AD) or psoriasis remains unclear.
OBJECTIVE
We sought to determine the differential expression profiles of circRNAs in peripheral blood mononuclear cells between healthy controls and AD patients, and explore the mechanisms underlying the effects of circRNAs on the pathogenesis of AD.
METHODS
The differential expression profiles of circRNAs were analyzed by circRNA microarray. In vitro function and mechanisms by which circRNAs regulate macrophage-mediated inflammation were detected by reverse transcription quantitative PCR, Western blot analysis, RNA stability assay, immunoprecipitation, ELISA, and methylated RNA immunoprecipitation assay. In vivo roles of circRNAs were determined in 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis and imiquimod (IMQ)-induced psoriasis mouse model.
RESULTS
We identified a functional unknown circRNA hsa_circ_0004287 from 88750 circRNAs, which was upregulated in peripheral blood mononuclear cells of both AD and psoriasis patients, and was mainly expressed by macrophages under inflammatory conditions. Hsa_circ_0004287 inhibited M1 macrophage activation in vitro, and macrophage-specific overexpression of hsa_circ_0004287 alleviated skin inflammation in both AD- and psoriasis-like mice. Mechanistically, hsa_circ_0004287 reduced the stability of its host gene metastasis associated lung adenocarcinoma transcript 1 (MALAT1) by competitively binding to IGF2BP3 with MALAT1 in an N-methyladenosine (mA)-dependent manner. Lower levels of MALAT1 promoted the ubiquitination degradation of S100A8/S100A9, thereby impeding p38/mitogen-activated protein kinase phosphorylation and macrophage-mediated inflammation.
CONCLUSION
hsa_circ_0004287 inhibits M1 macrophage activation in an mA-dependent manner in AD and psoriasis, and may serve as a general therapeutic candidate for AD and psoriasis.
Topics: Adenosine; Animals; Dermatitis, Atopic; Humans; Inflammation; Leukocytes, Mononuclear; Macrophages; Mice; MicroRNAs; Psoriasis; RNA, Circular; RNA, Long Noncoding
PubMed: 34953789
DOI: 10.1016/j.jaci.2021.11.024 -
Phytomedicine : International Journal... Aug 2022Atopic dermatitis (AD), a common inflammatory skin disorder, severely affects the life quality of patients and renders heavy financial burden on patient's family. The...
BACKGROUND
Atopic dermatitis (AD), a common inflammatory skin disorder, severely affects the life quality of patients and renders heavy financial burden on patient's family. The Chinese medicine Viola yedoensis Makino formula (VYAC) has been widely used for treating various skin disorders. Previous studies have reported that VYAC is effective in relieving DNCB-induced AD and inflammation. However, the anti-inflammatory mechanism of VYAC is still ill-defined and poorly understood. This study aims to investigate the therapeutic effects of VYAC on DNCB-induced AD and to elucidate the underlying anti-inflammatory mechanisms.
METHODOLOGY
VYAC were extracted with 70% ethanol and lyophilized for use. AD mice were established by DNCB. The therapeutic effects of VYAC were evaluated by oral administration VYAC (150, 300 and 600 mg/kg) daily in vivo. The histopathological and immunohistochemistry were used to analyze skin lesion and macrophages infiltration, RT-qPCR and Elisa were used to analyze the inflammatory factors in skin tissues and serum. To explore the underlying mechanism of VYAC against AD in vitro. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were employed for macrophage polarization analysis. Flow cytometer, immunofluorescence and western blot were used to analyze M2 macrophages markers. STAT3 siRNA were transfected into both cells to validate the effects of VYAC-induced macrophages M2 polarization via JAK2/STAT3 signaling pathway.
RESULTS
VYAC ameliorated skin lesion of DNCB-induced AD mice by decreased clinical scores and epidermal thickness, decreased the level of pro-inflammatory factors (IL-1β, TNF-α and IL-18) and enhanced IL-10 anti-inflammatory factor level, inhibited macrophages infiltration and promoted M2 macrophages polarization in vivo. VYAC significantly promoted M2 macrophages polarization in vitro. It is observed that VYAC not only inhibited the phosphorylation of JAK2 and STAT3 in RAW264.7 cells and BMDMs, but also accelerated the translocation to the nucleus. What's more, VYAC reduced the polarization of M2 macrophage by activating JAK2/STAT3 signaling pathway was observed in both cells.
CONCLUSIONS
Our findings demonstrate that VYAC significantly ameliorates skin lesion of DNCB-induced AD mice and reduces the levels of inflammatory factors by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization.
Topics: Animals; Anti-Inflammatory Agents; Cell Polarity; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Drugs, Chinese Herbal; Janus Kinase 2; Macrophages; Mice; Mice, Inbred BALB C; Plant Extracts; STAT3 Transcription Factor; Signal Transduction; Viola
PubMed: 35689898
DOI: 10.1016/j.phymed.2022.154228 -
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 -
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 -
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 -
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 -
Journal of Ethnopharmacology Sep 2023The main clinical manifestations of eczema include itching, erythema, swelling and pain. Currently, allergies and TH1/TH2 cytokine imbalances are significant causes of...
ETHNOPHARMACOLOGICAL RELEVANCE
The main clinical manifestations of eczema include itching, erythema, swelling and pain. Currently, allergies and TH1/TH2 cytokine imbalances are significant causes of eczema. TCM believes that eczema is mainly caused by incongruity between dry and wet. Wenguanmu ointment is a classic Mongolian medicine, which mainly composed of Xanthoceras sorbifolia Bunge, Coptis chinensis Franch and Bezoar. These ingredients can clear heat and dampness, dispel wind and dehumidification, anti-inflammatoryad analgesic. In this study, it was found that Wenguanmu ointment can treat eczema with anti-inflammatory, analgesic and antipruritic.
AIM OF THE STUDY
In this study, the content of main components in Wenguanmu ointment was tested. Moreover, the therapeutic effect and mechanism of Wenguanmu ointment on eczema model mice were studied.
MATERIALS AND METHODS
Kunming mice (25 ± 2 g) were randomly divided into 6 groups: Control group; Model group; Vehicle group; Wenguanmu ointment group; Compound dexamethasone acetate cream group; Chushizhiyang ointment group. The eczema mouse model was established by DNCB. HPLC and TLC tests were used to determine the content of the main components in Wenguanmu ointment. HE staining was used to assess skin damage in mice. In order to detect the anti-inflammatory effect of Wenguanmu ointment on eczema, The levels of IgE, TNF-α, IFN-γ, COX-2 and IL-4 in serum was measured by ELISA. Genecards and Online Mendelian Inheritance in Man databases were used to analyze potential target gene predictions, and it was speculated that Wenguanmu ointment was associated with NF-κB signaling pathway and chemokine signaling pathway. To detect this inference, RT-qPCR and western blotting were used to detect protein and mRNA levels of CKLF-1, IκB-α, and NF-κB.
RESULTS
Wenguanmu ointment can repress the symptoms of eczema caused by 2, 4-dinitrochlorobenzene, and inhibit the level of serum immunoglobulin E. Simultaneously it restrain the elevation of miscellaneous pro-inflammatory cytokines and chemokines, as well as reducing the expression of CKLF-1 and NF-κB protein in the nucleus, and increasing the protein expression of IκB to improve eczema.
CONCLUSIONS
The ameliorating effect of Wenguanmu ointment on eczema lesions can play a importment role by inhibiting the CKLF-1/NF-κB pathway.
Topics: Mice; Animals; NF-kappa B; Medicine, Mongolian Traditional; Ointments; Cytokines; Inflammation; Eczema; Anti-Inflammatory Agents
PubMed: 37116728
DOI: 10.1016/j.jep.2023.116549