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Molecular Medicine Reports May 2021Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects quality of life. Quinine is a bitter taste receptor agonist that exhibits...
Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects quality of life. Quinine is a bitter taste receptor agonist that exhibits antimalarial effects. The aim of the present study was to examine the therapeutic effects of quinine in AD‑like mice. AD was induced with 2,4‑dinitrochlorobenzene, and the mice were treated with 10 mg/kg quinine for 1, 4 and 7 days. A total of 60 BALB/c mice were divided into the following groups: Healthy, AD‑like, AD‑like + quinine and healthy + quinine, with 1, 4 and 7 days groups for each treatment. Blood was extracted from all mice and ELISA was performed to detect immunoglobulin E (IgE) levels. H&E‑stained tissue sections were prepared from skin lesions on the backs of the mice and pathological changes were observed. Cytokines were detected via ELISA, and the filaggrin (FLG) and kallikrein‑7 (KLK7) proteins were detected via western blotting and immunohistochemistry. IKKα and NF‑κB mRNA were analyzed via reverse transcription‑quantitative PCR. Quinine ameliorated skin damage in the AD‑like mice, reduced IgE expression in the blood, inhibited expression of IKKα and NF‑κB, reduced cytokine secretion, reduced KLK7 expression, reduced scratching frequency, increased FLG expression and repaired the skin barrier. These results suggested that quinine exhibited therapeutic effects in AD‑like mice.
Topics: Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; I-kappa B Kinase; Immunoglobulin E; Kallikreins; Male; Mice, Inbred BALB C; NF-KappaB Inhibitor alpha; NF-kappa B; Quinine; Receptor, Fibroblast Growth Factor, Type 1; Signal Transduction; Skin; Mice
PubMed: 34240224
DOI: 10.3892/mmr.2021.11952 -
Pharmaceutics Jul 2023Hydrogen sulfide (HS) is particularly produced in the skin, where it participates in the regulation of inflammation, pruritus, cytoprotection, scarring, and...
Hydrogen sulfide (HS) is particularly produced in the skin, where it participates in the regulation of inflammation, pruritus, cytoprotection, scarring, and angiogenesis. In this study, we compared the effects of dexamethasone (Dex) with two HS-releasing Dex derivatives in a murine model of atopic dermatitis (AD) induced by topical application of 2,4-dinitrochlorobenzene (DNCB). After sensitization with DNCB, the animals were topically treated for five consecutive days with either the HS-releasing compounds 4-hydroxy-thiobenzamide (TBZ) and 5-(p-hydroxyphenyl)-1,2-dithione-3-thione (ADT-OH), Dex, or the derivatives Dex-TBZ or Dex-ADT. Topical treatment with equimolar doses of either Dex, Dex-TBZ, or Dex-ADT resulted in similar reductions in dermatitis score, scratching behavior, edema, eosinophilia, splenomegaly, and histological changes. In contrast with Dex, the HS-releasing derivatives prevented IL-4 elevation and oxidative modification of skin proteins. On an equimolar dose basis, Dex-TBZ, but not Dex-ADT, promoted the elevation of endogenous HS production and GPx activity. Neither Dex-TBZ nor Dex-ADT decreased GR activity or caused hyperglycemia, as observed with Dex treatment. We conclude that the presence of HS-releasing moieties in the Dex structure does not interfere with the anti-inflammatory effects of this corticosteroid and adds beneficial therapeutical actions to the parent compound.
PubMed: 37514093
DOI: 10.3390/pharmaceutics15071907 -
BioMed Research International 2022and scopoletin are widely used in oriental Eastern medicine and are often consumed as teas. In this study, proinflammatory cytokines expressed in human keratinocytes...
and scopoletin are widely used in oriental Eastern medicine and are often consumed as teas. In this study, proinflammatory cytokines expressed in human keratinocytes (HaCaT) were induced by skin diseases caused by 2,4-dinitrochlorobenzene (DNCB) and tumor necrosis factor alpha (TNF-)/interferon gamma (IFN-). The inhibitory activity of EtOH extract (LBE) and scopoletin on proinflammatory cytokines and chemokines was investigated. In the DNCB-induced animal model, oral administration of LBE inhibited skin lesions and proinflammatory cytokines and chemokines and showed inhibitory effects . Additionally, as a result of examining the efficacy of scopoletin isolated from , scopoletin in HaCaT cells showed inhibitory effects on proinflammatory cytokines and chemokines. It shows promise in the treatment of chronic skin diseases.
Topics: Animals; Anti-Inflammatory Agents; Chemokines; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Humans; Inflammation; Interferon-gamma; Lycium; Mice; Mice, Inbred BALB C; Plant Extracts; Scopoletin; Skin; Tumor Necrosis Factor-alpha
PubMed: 36158872
DOI: 10.1155/2022/2475699 -
The Journal of Investigative Dermatology Jun 2023
Topics: Humans; Dinitrochlorobenzene; Dermatitis, Contact; Hypersensitivity; TRPA1 Cation Channel
PubMed: 36634816
DOI: 10.1016/j.jid.2022.12.014 -
Journal of Ethnopharmacology Jul 2024Yu-Ping-Feng-San (YPF) is a traditional Chinese medicine formula that has therapeutic effects on allergic diseases such as allergic rhinitis and asthma. However, its...
ETHNOPHARMACOLOGICAL RELEVANCE
Yu-Ping-Feng-San (YPF) is a traditional Chinese medicine formula that has therapeutic effects on allergic diseases such as allergic rhinitis and asthma. However, its potential efficacy and mechanism in the treatment of atopic dermatitis (AD) has not been extensively illustrated.
AIM OF THE STUDY
The purpose of this study was to investigate the efficacy and possible mechanisms of YPF in AD pathogenesis.
METHODS
Network pharmacology and GEO data mining were adopted to firstly identify the potential mechanisms of YPF on AD. Then DNCB induced-AD murine model was established to test the efficacy of YPF and verify its effects on inflammatory cytokines and NF-κB pathway. In addition, molecular docking was performed to detect the binding affinity of YPF's active components with NF-κB pathway related molecules.
RESULTS
Network pharmacology and human data mining suggested that YPF may act on the NF-κB pathway in AD pathogenesis. With DNCB mice model, we found that YPF significantly improved AD symptoms, reduced SCORAD scores, and alleviated skin tissue inflammation in mice. At the same time, the expression of inflammatory cytokines, TNF-α, sPLA2-IIA and IL-6, was down-regulated. Moreover, YPF suppressed TLR4/MyD88/NF-κB pathway in situ in a dose-dependent manner. Molecular docking further confirmed that seven compounds in YPF had exceptional binding properties with TNF-α, IL-6 and TLR4.
CONCLUSION
YPF may help the recovery of AD by inhibiting the TLR4/MyD88/NF-κB pathway, which provides novel insights for the treatment of AD by YPF.
Topics: Animals; Dermatitis, Atopic; Toll-Like Receptor 4; NF-kappa B; Myeloid Differentiation Factor 88; Drugs, Chinese Herbal; Signal Transduction; Mice; Molecular Docking Simulation; Mice, Inbred BALB C; Male; Disease Models, Animal; Cytokines; Anti-Inflammatory Agents; Dinitrochlorobenzene; Network Pharmacology; Humans; Inflammation; Female
PubMed: 38604509
DOI: 10.1016/j.jep.2024.118092 -
Life Sciences Jan 2022This study was aimed to explore whether sacran polysaccharide has a therapeutic effect on atopic dermatitis (AD) and its possible mechanisms.
AIMS
This study was aimed to explore whether sacran polysaccharide has a therapeutic effect on atopic dermatitis (AD) and its possible mechanisms.
MATERIALS AND METHODS
2, 4-dinitrochlorobenzene (DNCB)-induced AD mice were treated with 0.2% Sacran, 0.5% Sacran and 0.1% tacrolimus. Through scoring dermatitis severity, measuring ear thickness, cracking behavior, open field test, we evaluated the therapeutic effect of Sacran on DNCB-induced AD mice. CD4 T cells and CD8 T cells were evaluated by flow cytometry. The relative expression of Ifng and Il4 were measured by real-time quantitative PCR.
KEY FINDINGS
Sacran could relieved the symptoms of DNCB-induced AD mice, such as AD score, ear thickness, and IgE release. Sacran may alleviate dermatitis by inhibiting Th2 activation and reducing IgE release.
SIGNIFICANCE
Our research further proved that polysaccharide Sacran has anti-dermatitis effects, and also clarified its mechanism of alleviating dermatitis by inhibiting the activation of Th2 cells and reducing the release of IgE, which provides a theoretical basis for the future clinical transformation of polysaccharide Sacran.
Topics: Animals; Dermatitis, Atopic; Dinitrochlorobenzene; Female; Immunoglobulin E; Indicators and Reagents; Inflammation; Mice; Mice, Inbred BALB C; Polysaccharides; Th2 Cells
PubMed: 34871665
DOI: 10.1016/j.lfs.2021.120205 -
ACS Applied Bio Materials Feb 2021Here, we report the different antioxidant and physiological effects of maghemite nanoparticles (γ-FeO NPs) obtained using various Fe: Fe molar ratios (FM1 = 1: 1, FM2 =...
Here, we report the different antioxidant and physiological effects of maghemite nanoparticles (γ-FeO NPs) obtained using various Fe: Fe molar ratios (FM1 = 1: 1, FM2 = 1: 2, and FM3 = 2: 3) via coprecipitation from ferrous/ferric salts. We investigated the physical, optical, and antioxidant properties of FM1, FM2, and FM3 nanoparticles by conducting UV, Raman, FTIR, and EDX spectroscopic analyses along with DPPH radical scavenging activity. Results showed the highest DPPH scavenging activity in the FM2 group (50.76%), while the activity in the FM1 and FM3 groups was 23.60% and 34.63%, respectively. In addition, topical application of nanoparticles induced significant but different anti-inflammatory and immunomodulatory effects in extract/2,4-dinitrochlorobenzene (DFE/DNCB)-sensitized BALB/c mice. The FM2 treatment alleviates more effectively the DFE/DNCB-induced atopic dermatitis-like (AD-like) symptoms in mouse ears (edema, excoriation, scaling, and hemorrhage). In comparison with the DFE/DNCB-sensitized mice, FM2 treatment greatly reduced the size and weight of the spleen and the lymph nodes. It also suppressed mast cell infiltration (2-fold) and reduced dermal and epidermal thickness in mice. In addition, FM2 treatment exhibited better inhibition of the mRNA levels of Th1 (IFN-γ and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, and IL-31), as well as the levels of various inflammation-related proteins (COX-2, iNOS, and TNF-α). Moreover, we demonstrated that an increasing proportion of Fe in Fe: Fe enhances the antioxidant activity and increases the anti-inflammatory and immunomodulatory effects of γ-FeO NPs in an AD mouse model. Thus, γ-FeO NPs could be used in the formulation of nonsteroidal drugs for AD treatment.
Topics: Animals; Anti-Inflammatory Agents; Cell Survival; Cytokines; Dermatitis, Atopic; Dermatophagoides farinae; Dinitrochlorobenzene; Ear, External; Female; Ferric Compounds; Free Radical Scavengers; Immunologic Factors; Iron; Magnetic Iron Oxide Nanoparticles; Mast Cells; Mice, Inbred BALB C; Signal Transduction; Tissue Extracts; Mice
PubMed: 35014478
DOI: 10.1021/acsabm.0c01092 -
International Journal of Molecular... Oct 2021Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has...
Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects on the skin, but its effect on mast cells has not yet been studied in detail. In this study, we used mast cells (RBL-2H3 cells) and mouse models to study the anti-allergic and inflammatory effects of neferine. First, we found that neferine inhibits the degranulation of mast cells and the expression of cytokines. In addition, we observed that when mast cells were stimulated by A23187/phorbol 12-myristate-13-acetate (PMA), the elevation of intracellular calcium was inhibited by neferine. The phosphorylation of the MAPK/NF-κB pathway is also reduced by pretreatment of neferine. The results of in vivo studies show that neferine can improve the appearance of dermatitis and mast cell infiltration caused by dinitrochlorobenzene (DNCB). Moreover, the expressions of barrier proteins in the skin are also restored. Finally, it was found that neferine can reduce the scratching behavior caused by compound 48/80. Taken together, our results indicate that neferine is a very good anti-allergic and anti-inflammatory natural product. Its effect on mast cells contributes to its pharmacological mechanism.
Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Benzylisoquinolines; Calcimycin; Calcium; Cell Line; Cell Movement; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Mast Cells; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; NF-kappa B; Phosphorylation; Signal Transduction
PubMed: 34681651
DOI: 10.3390/ijms222010994 -
Life Sciences Mar 2023Atopic dermatitis (AD) is a common chronic inflammatory skin disorder that affects up to 20 % of children and 10 % of adults worldwide; however, the exact molecular...
AIMS
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder that affects up to 20 % of children and 10 % of adults worldwide; however, the exact molecular mechanisms remain largely unknown.
MATERIALS AND METHODS
In this study, we used integrated transcriptomic and metabolomic analyses to study the potential mechanisms of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesions.
KEY FINDINGS
We found that DNCB induced AD-like skin lesions, including phenotypical and histomorphological alterations and transcriptional and metabolic alterations in mice. A total of 3413 differentially expressed metabolites were detected between DNCB-induced AD-like mice and healthy controls, which includes metabolites in taurine and hypotaurine metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, tryptophan metabolism, arachidonic acid metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism pathways. Furthermore, the differentially expressed genes associated (DEGs) with these metabolic pathways were analyzed using RNA sequencing (RNA-seq), and we found that the expression of pyrimidine metabolism-associated genes was significantly increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the glycolysis/gluconeogenesis, glucagon signaling pathway and pentose phosphate pathway-associated metabolic genes were dramatically altered.
SIGNIFICANCE
Our results explain the possible mechanism of AD at the gene and metabolite levels and provide potential targets for the development of clinical drugs for AD.
Topics: Mice; Animals; Dermatitis, Atopic; Dinitrobenzenes; Dinitrochlorobenzene; Transcriptome; Cytokines; Skin; Skin Diseases; Pyrimidines; Mice, Inbred BALB C
PubMed: 36746357
DOI: 10.1016/j.lfs.2023.121474 -
Archives of Toxicology Aug 2023MiRNAs are non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Although allergic contact dermatitis has been studied extensively,...
MiRNAs are non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Although allergic contact dermatitis has been studied extensively, few studies addressed miRNA expression and their role in dendritic cell activation. The main aim of this work was to investigate the role of miRNAs in the underlying mechanism of dendritic cell maturation induced by contact sensitizers of different potency. Experiments were conducted using THP-1-derived immature DCs (iDCs). Contact allergens of different potency were used: p-benzoquinone, Bandrowski's base, and 2,4-dinitrochlorobenzene as extreme; nickel sulfate hexahydrate, diethyl maleate and 2-mercaptobenzothiazole as moderate; and α-hexyl cinnamaldehyde, eugenol, and imidazolidinyl urea as weak. Selective inhibitor and mimic miRNAs were then used and several cell surface markers was evaluated as targets. Also, patients patch tested with nickel were analyzed to determine miRNAs expression. Results indicate an important role of miR-24-3p and miR-146a-5p in DCs activation. miR-24-3p was up-regulated by extreme and weak contact allergens, while miR-146a-5p was up-regulated by weak and moderate contact allergens and down-regulated only by the extreme ones. Also, the involvement of PKCβ in contact allergen-induced miR-24-3p and miR-146a-5p expression was demonstrated. Furthermore, the expression of the two miRNAs maintains the same trend of expression in both in vitro and in human conditions after nickel exposure. Results obtained suggest the involvement of miR-24 and miR-146a in DCs maturation process in the proposed in vitro model, supported also by human evidences.
Topics: Humans; Nickel; MicroRNAs; Dermatitis, Allergic Contact; Allergens; Dendritic Cells
PubMed: 37326882
DOI: 10.1007/s00204-023-03542-z