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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 -
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 -
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 -
Marine Drugs Aug 2023Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common...
Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide limited relief and have some side effects. Therefore, there is a need to develop new effective therapies to treat AD. -oxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid. Relevant studies have shown that zoanthamine alkaloids have many pharmacological and biological activities, including anti-lymphangiogenic functions. However, there are no studies on the use of -oxyzoanthamine on the skin. In this paper, -oxyzoanthamine has been shown to have potential in the treatment of atopic dermatitis. Through in vitro studies, it was found that -oxyzoanthamine inhibited the expression of cytokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Atopic dermatitis-like skin inflammation was induced in a mouse model using 2,4-dinitrochlorobenzene (DNCB) in vivo. The results showed that -oxyzoanthamine significantly decreased skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear thickness, and spleen weight, while also increasing surface skin hydration. These results indicate that -oxyzoanthamine from zoanthid has good potential as an alternative medicine for treating atopic dermatitis or other skin-related inflammatory diseases.
Topics: Adult; Child; Humans; Animals; Mice; Dinitrochlorobenzene; Dermatitis, Atopic; Skin; Pruritus; Keratinocytes
PubMed: 37623728
DOI: 10.3390/md21080447 -
Inflammation Jun 2024A topic dermatitis (AD) is a common chronic and recurrent skin disorder. The protective effects of sodium butyrate (NaB), a metabolite of short-chain fatty acid...
A topic dermatitis (AD) is a common chronic and recurrent skin disorder. The protective effects of sodium butyrate (NaB), a metabolite of short-chain fatty acid breakdown by the gut microbiota, have been widely reported in numerous inflammatory diseases. However, the effect of NaB treatment alone on AD has not been reported. In the current study, AD was induced in BALB/c mice with 2,4-dinitrochlorobenzene (DNCB) for 28 days with NaB (200 mg/kg) treatment by gavage. NaB attenuated AD-induced skin bleeding, scarring, dryness, abrasions and erosions. In addition, NaB inhibited inflammatory cells infiltration and attenuated the expression of inflammatory cytokines and chemokines. Mechanistically, NaB reduced histone deacetylase 3 (HDAC3) expression and NF-κB p65 nuclear translocation by increasing the lysine acetylation levels of STAT1 and NF-κB p65 in AD. Taken together, our study suggests that NaB inhibits inflammatory mediators and ameliorates AD by inhibiting HDAC3 expression, thereby upregulating STAT1 and NF-κB p65 lysine acetylation levels and reducing NF-κB p65 nuclear translocation. Therefore, this study provides a new theoretical basis for NaB in the treatment of AD.
Topics: Animals; Histone Deacetylases; STAT1 Transcription Factor; Mice; Butyric Acid; Mice, Inbred BALB C; Dermatitis, Atopic; NF-kappa B; Inflammation; Signal Transduction; Transcription Factor RelA
PubMed: 38159175
DOI: 10.1007/s10753-023-01955-7 -
Frontiers in Immunology 2024Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal...
BACKGROUND
Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD).
METHODS
To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation.
RESULTS
Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK.
DISCUSSION
Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Skin; Reactive Oxygen Species; Immunoglobulin E; Anti-Inflammatory Agents; Inflammation; Imidazoles
PubMed: 38533495
DOI: 10.3389/fimmu.2024.1324026 -
Chemical Research in Toxicology Dec 2023Hemoglobin (Hb) adducts are widely used in human biomonitoring due to the high abundance of hemoglobin in human blood, its reactivity toward electrophiles, and adducted...
Hemoglobin (Hb) adducts are widely used in human biomonitoring due to the high abundance of hemoglobin in human blood, its reactivity toward electrophiles, and adducted protein stability for up to 120 days. In the present paper, we compared three methods of analysis of hemoglobin adducts: mass spectrometry of derivatized N-terminal Val adducts, mass spectrometry of N-terminal adducted hemoglobin peptides, and limited proteolysis mass spectrometry . Blood from human donors was incubated with a selection of contact allergens and other electrophiles, after which hemoglobin was isolated and subjected to three analysis methods. We found that the FIE method was able to detect and reliably quantify N-terminal adducts of acrylamide, acrylic acid, glycidic acid, and 2,3-epoxypropyl phenyl ether (PGE), but it was less efficient for 2-methyleneglutaronitrile (2-MGN) and failed to detect 1-chloro-2,4-dinitrobenzene (DNCB). By contrast, bottom-up proteomics was able to determine the presence of adducts from all six electrophiles at both the N-terminus and reactive hemoglobin side chains. Limited proteolysis mass spectrometry, studied for four contact allergens (three electrophiles and a metal salt), was able to determine the presence of covalent hemoglobin adducts with one of the three electrophiles (DNCB) and coordination complexation with the nickel salt. Together, these approaches represent complementary tools in the study of the hemoglobin adductome.
Topics: Humans; Dinitrochlorobenzene; Hemoglobins; Mass Spectrometry
PubMed: 37963067
DOI: 10.1021/acs.chemrestox.3c00294 -
Allergy, Asthma, and Clinical... Nov 2023Although numerous studies have suggested a negative correlation between Helicobacter pylori (H. pylori) infection and allergies, there has been limited research on the...
BACKGROUND
Although numerous studies have suggested a negative correlation between Helicobacter pylori (H. pylori) infection and allergies, there has been limited research on the relationship between H. pylori infections and atopic dermatitis (AD). The present study aimed to investigate the effects of H. pylori infection in an AD mouse model and identify potential mechanisms related to type 2 immunity, skin barrier defects, and pruritus.
METHODS
A model of AD-like symptoms was established with 2,4-dinitrochlorobenzene (DNCB) after infection of the gastric cavity with H. pylori. Analysis of the expression of key inflammatory cytokines and serum levels of immunoglobulin E (IgE) was based on enzyme-linked immunosorbent assay (ELISA). The expression of filaggrin (FLG) and loricrin (LOR) were analyzed by immunohistochemistry staining. The evaluation of STAT1, STAT3, phosphorylated STAT1 (phospho-STAT1), and phosphorylated STAT3 (phospho-STAT1) expression levels in skin lesions was performed using western blot.
RESULTS
The present study showed that the H. pylori-positive AD group (HP+AD+) exhibited milder skin lesions, including erythema, erosion, swelling, and scaling, than the H. pylori-negative AD group (HP-AD+). Additionally, HP+AD+ displayed lower levels of IgE in serum, and downregulated expression of interleukins 4 and 31 (IL-4 and IL-31) in serum. Furthermore, HP+AD+ demonstrated higher expression of filaggrin and loricrin than HP-AD+. Notably, H. pylori significantly reduced the amount of phosphorylated STAT1 and STAT3.
CONCLUSION
Helicobacter pylori infection negatively regulates the inflammatory response by affecting inflammatory factors in the immune response, and repairs the defective epidermal barrier function. In addition, H. pylori infection may reduce IL-31, thereby alleviating pruritus. These effects may be associated with the inhibition of JAK-STAT signaling activation.
PubMed: 37978564
DOI: 10.1186/s13223-023-00851-x -
Journal of Ethnopharmacology Jan 2024Polygonum perfoliatum L. (PP) is classified as a heat-clearing and detoxifying agent in traditional Chinese medicine, and is believed to possess therapeutic properties...
ETHNOPHARMACOLOGICAL RELEVANCE
Polygonum perfoliatum L. (PP) is classified as a heat-clearing and detoxifying agent in traditional Chinese medicine, and is believed to possess therapeutic properties for treating eczema, furuncles, and venomous snake bites. Previous studies have demonstrated that PP extract exhibits multiple bioactivities, including antibacterial, anti-inflammatory, antitumor, antioxidation, and antiviral properties. However, no existing studies have evaluated the effects of PP on animal models of atopic dermatitis (AD)-like skin symptoms, which are closely associated with traditional ethnic usage.
AIM OF THE STUDY
In present study, therefore, we aimed to explore the potential anti-atopic effect of Polygonum perfoliatum L. ethanol extract (PPE) in 2,4-Dinitrochlorobenzene (DNCB)-induced dermatitis-like skin lesions.
MATERIALS AND METHODS
For reaching this aim, DNCB-induced mice with AD-like skin inflammation were subjected to topical administration of PPE gels for a period of 21 days, and subsequently, the biological impacts of PPE were evaluated.
RESULTS
PPE gels effectively mitigated AD-like skin symptoms induced by DNCB in mice, as demonstrated by a marked reduction in epidermal thickness and dermatitis severity. Moreover, PPE significantly decreased the production of various cytokines, including TNF-α, IL-6, IL-1β, IL-4, IL-5, IL-13 and IgE, in addition to suppressed the production of key inflammation-related enzymes (iNOS and COX-2) and decreased the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in AD-like skin samples. Furthermore, PPE treatment inhibited the abnormally elevated CD4+/CD8+ ratio in DNCB-induced AD mice. The results of the skin irritation test revealed that PPE exhibited no adverse toxicity in mice at dose of 10 mg/day.
CONCLUSIONS
PPE exhibits potential as a safe therapeutic agent for atopic dermatitis by efficiently mitigating DNCB-induced atopic symptoms and diminishing inflammation, and does not carry the risk of over-immunosuppression or treatment-associated adverse effects.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Skin; Polygonum; Ethanol; Cytokines; Inflammation; Skin Diseases; NF-kappa B; Gels; Mice, Inbred BALB C
PubMed: 37827300
DOI: 10.1016/j.jep.2023.117288 -
Nutrients Feb 2024Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. (EA),...
Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. (EA), an annual winter plant belonging to the family Asteraceae, possesses anti-inflammatory, cytoprotective, and antioxidant activities. In this study, we hypothesized that extract (EAE) could be an effective agent for ameliorating AD-like symptoms. To confirm this hypothesis in vitro, we used HO-stimulated human keratinocytes (HaCaT cells) to demonstrate that pre-treatment with EAE protected against oxidative stress. HaCaT cells pretreated with EAE and stimulated with HO showed decreased intracellular malondialdehyde content, increased superoxide dismutase activity, and reduced intracellular reactive oxygen species accumulation. To verify the in vivo hypothesis based on the intracellular results, an AD disease mouse model was induced with 1-chloro-2,4-dinitrobenzene (DNCB), and EAE was orally administered at a non-toxic concentration according to the toxicity evaluation results. The results showed that AD disease models in BALB/c mice exhibited reduced ear epidermal thickness, scratching behavior, and mast cell infiltration. In conclusion, our results indicate that EAE has the potential to improve AD by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Skin; Dinitrochlorobenzene; Erigeron; NF-E2-Related Factor 2; Dinitrobenzenes; Heme Oxygenase-1; Hydrogen Peroxide; Tumor Necrosis Factor-alpha; Mice, Inbred BALB C; Cytokines
PubMed: 38337735
DOI: 10.3390/nu16030451