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The Korean Journal of Physiology &... Jul 2024Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and...
Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.
PubMed: 38926838
DOI: 10.4196/kjpp.2024.28.4.303 -
International Immunopharmacology Jun 2024Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we...
Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we started the present study, first possible effects of SCD on AD were predicted using network pharmacology. Next, dinitrochlorobenzene was used to establish a mouse model of AD. After successful modelling, the SCD were administered intragastrically to treat the mice. Eventually, the KEGG pathway enrichment analysis indicated that SCD improved AD mainly through effects on inflammation and the gut microbiota. The experimental findings revealed that SCD treatment attenuated AD symptoms and downregulate the characteristic immune factors, namely IL-4, IL-6 and IgE. Moreover, it promoted a balance between Th1/Th2 cells. Furthermore, the itch signaling pathways involving H1R/PAR-2/TRPV1 were inhibited. The 16S rRNA sequencing results indicated that SCD administration influenced the Firmicutes/Bacteroidetes ratio at the phylum level by augmenting the relative proportions of Lactobacillaceae and Muribaculaceae at the family and genus levels, while decreasing the abundances of Lactococcus and Ruminococcus. These findings suggest that internal administration of SCD is an effective therapeutic approach for AD. We suggest that SCD may be an alternative therapy for the treatment of AD.Additionally, it could offer valuable insights into the pathogenesis of AD and the development of innovative therapeutic agents.
PubMed: 38901246
DOI: 10.1016/j.intimp.2024.112479 -
Biomedicine & Pharmacotherapy =... Jul 2024Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the...
Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the predominant iridoid glycoside in Morinda officinalis How roots, which has previously shown promise in alleviating AD symptoms. This study aimed to systematically investigate the pharmacological effects of monotropein on AD using a 2, 4-dinitrochlorobenzene (DNCB)/Dermatophagoides farinae extract (DFE)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated keratinocytes. Oral administration of monotropein demonstrated a significant reduction in AD phenotypes, including scaling, erythema, and increased skin thickness in AD-induced mice. Histological analysis revealed a marked decrease in immune cell infiltration in skin lesions. Additionally, monotropein effectively downregulated inflammatory markers, encompassing pro-inflammatory cytokines, T helper (Th)1 and Th2 cytokines, and pro-inflammatory chemokines in skin tissues. Notably, monotropein also led to a considerable decrease in serum immunoglobulin (Ig)E and IgG2a levels. At a mechanistic level, monotropein exerted its anti-inflammatory effects by suppressing the phosphorylation of Janus kinase / signal transducer and activator of transcription proteins in both skin tissues of AD-induced mice and TNF-α/IFN-γ-stimulated keratinocytes. In conclusion, monotropein exhibited a pronounced alleviation of AD symptoms in the experimental models used. These findings underscore the potential application of monotropein as a therapeutic agent in the context of AD, providing a scientific basis for further exploration and development.
Topics: Animals; Dermatitis, Atopic; Signal Transduction; Mice; Janus Kinases; Skin; Keratinocytes; Cytokines; Mice, Inbred BALB C; STAT Transcription Factors; Humans; Dinitrochlorobenzene; Anti-Inflammatory Agents; Female; Disease Models, Animal; Inflammation; Immunoglobulin E; Dermatophagoides farinae; Iridoids
PubMed: 38861857
DOI: 10.1016/j.biopha.2024.116911 -
Scientific Reports Jun 2024Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies....
Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies. Sargassum serratifolium, an algal species with diverse bioactive substances, is investigated in this study for its potential benefits as a therapeutic agent for atopic dermatitis. RNA sequencing of LPS-stimulated macrophages treated with ethanolic extract of Sargassum serratifolium (ESS) revealed its ability to inhibit a broad range of inflammation-related signaling, which was proven in RAW 264.7 and HaCaT cells. In DNCB-induced BALB/c or HR-1 mice, ESS treatment improved symptoms of atopic dermatitis within the skin, along with histological improvements such as reduced epidermal thickness and infiltration of mast cells. ESS showed a tendency to improve serum IgE levels and inflammation-related cytokine changes, while also improving the mRNA expression levels of Chi3l3, Ccr1, and Fcεr1a genes in the skin. Additionally, ESS compounds (sargachromanol (SCM), sargaquinoic acid (SQA), and sargahydroquinoic acid (SHQA)) mitigated inflammatory responses in LPS-treated RAW264.7 macrophages. In summary, ESS has an anti-inflammatory effect and improves atopic dermatitis, ESS may be applied as a therapeutics for atopic dermatitis.
Topics: Animals; Dermatitis, Atopic; Sargassum; Mice; RAW 264.7 Cells; Disease Models, Animal; Mice, Inbred BALB C; Dinitrochlorobenzene; Humans; Ethanol; Plant Extracts; Macrophages; Skin; Anti-Inflammatory Agents; Immunoglobulin E; Cytokines
PubMed: 38834629
DOI: 10.1038/s41598-024-62828-z -
Journal of Inflammation Research 2024Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in...
PURPOSE
Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.
METHODS
This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10, IFN-γ and FoxP3CD4T cells in murine spleen.
RESULTS
It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3, IL-10 and IFN-γ CD4T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.
CONCLUSION
These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.
PubMed: 38751687
DOI: 10.2147/JIR.S454325 -
ACS Omega Apr 2024The traditional prescription of Liangxue-Qushi-Zhiyang decoction (LQZ) has been demonstrated to be efficacious in treating atopic dermatitis (AD), a chronic inflammatory...
The traditional prescription of Liangxue-Qushi-Zhiyang decoction (LQZ) has been demonstrated to be efficacious in treating atopic dermatitis (AD), a chronic inflammatory skin disorder marked by intense itching, redness, rashes, and skin thickening. Nevertheless, there has been an inadequate systematic exploration of the potential targets, biological processes, and pathways for AD treatment through LQZ. The study objective was to evaluate the efficacy and possible mechanism of LQZ in AD mice. In our study, we identified the primary compounds of LQZ, analyzed hub targets, and constructed a network. Subsequently, the predicted mechanisms of LQZ in AD were experimentally studied and validated in vivo, as determined by network pharmacological analysis. A total of 80 serum components of LQZ were identified through ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS), among which 49 compounds were absorbed into the bloodstream. Our results indicated that LQZ targets six putative key factors in the MAPK signaling pathway, which play essential roles in AD, namely, EGFR, p-MAPK1/3, p-MAPK14, IL-1β, IL-6, and TNF-α. We observed spleen coefficient, dermatitis scores, and ear thickness were all downregulated in 2,4-dinitrochlorobenzene (DNCB)-induced mice after LQZ treatment. Histological analysis of the dorsal and ear skin further revealed that LQZ significantly decreased skin inflammation, epidermal thickness, and mast cell numbers compared to the DNCB group. Our study demonstrated the effectiveness of LQZ in reducing epidermal and dermal damage in a mouse model of AD. Furthermore, our findings suggest that downregulating the MAPK signaling pathway could be a potential therapeutic strategy for the treatment of AD.
PubMed: 38680355
DOI: 10.1021/acsomega.3c09218 -
Explore (New York, N.Y.) Mar 2024Eczema and contact dermatitis are relatively common, non-life-threatening disease, but can reduce the patient's quality-of-life when it becomes chronic. This study...
INTRODUCTION
Eczema and contact dermatitis are relatively common, non-life-threatening disease, but can reduce the patient's quality-of-life when it becomes chronic. This study describes two cases of bee venom acupuncture (BVA) and herbal medicine (San Wu Huangqin decoction; SWH) co-treatment for hand eczema and contact dermatitis, then confirms the effect of the combination therapy in an in vivo model of eczema.
CASE PRESENTATION
A 56-year-old female (case 1) and a 33-year-old male (case 2) presented to the clinic with symptoms of itching and erythema (case 1), and scaliness (case 2) on both hands. Both were diagnosed with hand eczema and contact dermatitis based on examination of the erythema and scaliness. They were treated with BVA and SWH for three months. The lesions were healed and had not recurred after 1 and 3 years of follow-up. A mouse study was conducted by repeated application of 2,4-dinitrochlorobenzene (DNCB) to induce eczema-like contact dermatitis in Balb/c mice. In a DNCB-induced eczema-like contact dermatitis model, BVA and SWH co-administration synergistically improved clinical symptoms seen in eczema. Also, they improved histological changes of the skin, suppressed immune cell infiltration, and decreased inflammatory cytokines and immunoglobulin E in the serum.
CONCLUSION
This study suggests BVA and SWH could be an alternative treatment for eczema and contact dermatitis.
PubMed: 38637265
DOI: 10.1016/j.explore.2024.03.002 -
Laboratory Animal Research Apr 2024Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (T2) and type-1 (T1) helper T cell-biased immune responses at...
BACKGROUND
Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (T2) and type-1 (T1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on AD-like skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase).
RESULTS
The paradigm of T2 or T1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants, an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward T2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/IgG2a ratios in acute AD, but both ratios increased during the chronic stage.
CONCLUSIONS
Our results suggest that ADFE concomitantly suppresses the T2 predominant response in acute AD, as well as the T1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.
PubMed: 38582857
DOI: 10.1186/s42826-024-00201-x -
Pharmaceuticals (Basel, Switzerland) Feb 2024Georgi and Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for...
Georgi and Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) and to predict the underlying therapeutic mechanisms and involved pathways using network pharmacological analysis. Treatment with SRE accelerated the development of AD-like lesions, improving thickness and edema of the epidermis. Moreover, administering the SRE to AD-like mice suppressed immunoglobulin E and interleukin-4 cytokine and reduced T lymphocyte differentiation. In silico, network analysis was used to predict the exact genes, proteins, and pathways responsible for the therapeutic effect of the SRE against DNCB-induced AD. These results indicated that the SRE exerted protective effects on the DNCB-induced AD-like model by attenuating histopathological changes and suppressing the levels of inflammatory mediators. Therefore, the SRE can potentially be a new remedy for improving AD and other inflammatory diseases and predicting the intracellular signaling pathways and target genes involved. This therapeutic effect of the SRE on AD can be used to treat DNCB-induced AD and its associated symptoms.
PubMed: 38543055
DOI: 10.3390/ph17030269 -
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