-
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 -
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 -
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 -
Scientific Reports Mar 2024Given the intricate etiology and pathogenesis of atopic dermatitis (AD), the complete cure of AD remains challenging. This study aimed to investigate if topically...
Given the intricate etiology and pathogenesis of atopic dermatitis (AD), the complete cure of AD remains challenging. This study aimed to investigate if topically applying N-benzyl-N-methyldecan-1-amine (BMDA), derived from garlic, and its derivative [decyl-(4-methoxy-benzyl)-methyl-1-amine] (DMMA) could effectively alleviate AD-like skin lesions in 2,4-dinitrochlorobenzene (DNCB)-treated mice. Administering these compounds to the irritated skin of DNCB-treated mice significantly reduced swelling, rash, and excoriation severity, alongside a corresponding decrease in inflamed epidermis and dermis. Moreover, they inhibited spleen and lymph node enlargement and showed fewer infiltrated mast cells in the epidermis and dermis through toluidine-blue staining. Additionally, they led to a lower IgE titer in mouse sera as determined by ELISA, compared to vehicle treatment. Analyzing skin tissue from the mice revealed decreased transcript levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6), IL-4, iNOS, and COX-2, compared to control mice. Simultaneously, the compounds impeded the activation of inflammation-related signaling molecules such as JNK, p38 MAPK, and NF-κB in the mouse skin. In summary, these findings suggest that BMDA and DMMA hold the potential to be developed as a novel treatment for healing inflammatory AD.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Garlic; Skin; Cytokines; Amines; NF-kappa B; Mice, Inbred BALB C; Maleic Anhydrides
PubMed: 38514712
DOI: 10.1038/s41598-024-56496-2 -
Veterinary Medicine and Science May 2024Probiotic strains have the potential to modulate immune responses, reduce intestinal inflammation, normalize intestinal mucosal function and decrease allergic reactions.
BACKGROUND
Probiotic strains have the potential to modulate immune responses, reduce intestinal inflammation, normalize intestinal mucosal function and decrease allergic reactions.
OBJECTIVE
This study aimed to investigate the effect of oral probiotic supplements containing Bacillus subtilis and Bacillus coagulans spores on clinical symptoms, haematological factors and immune responses to allergic contact dermatitis in dogs induced by dinitrochlorobenzene (DNCB).
METHODS
DNCB was injected subcutaneously into the scapular region of 20 healthy adult dogs of both sexes, divided into four groups, to induce experimental allergic contact dermatitis. Dogs in Group 1 received food without probiotics or medication. Oral prednisolone was administered to Group 2 for 30 days at a dosage of 0.25 mg/kg every other day. The dogs in Group 3 were treated with a combination of oral prednisolone and probiotics. The dogs in Group 4 were fed daily with a mixture of 10 B. subtilis and B. coagulans bacteria for 30 days. The immune system responses and related gene expression were analysed in the treated animals.
RESULTS
The administration of probiotics for 30 days resulted in a reduction in clinical symptoms and duration of wound repair. The probiotics treatment also significantly increased the serum bactericidal effects against Staphylococcus aureus and Escherichia coli. It enhanced both the classic and alternative activity of the complement, as well as lysozyme activity. Additionally, the probiotics led to higher total immunoglobulin levels and significant reductions in anti-trypsin and C-reactive protein levels. Furthermore, the expression of IgE, induction of interferon-gamma and IL-4 genes were also reduced.
CONCLUSIONS
According to the results, B. subtilis and B. coagulans can be further investigated as a viable alternative to corticosteroids in treating allergic contact dermatitis in dogs.
Topics: Male; Female; Dogs; Animals; Bacillus subtilis; Bacillus coagulans; Dinitrochlorobenzene; Spores, Bacterial; Dermatitis, Allergic Contact; Prednisolone; Dog Diseases
PubMed: 38501344
DOI: 10.1002/vms3.1410 -
Life Sciences May 2024Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects....
AIMS
Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects. However, its potential effects on atopic dermatitis (AD) have not been elucidated. This study aimed to evaluate the efficacy of UDCA in inhibiting the inflammatory response and alleviating lesions in AD-like mice.
MAIN METHODS
To investigate the efficacy of UDCA in AD-like inflammatory responses, tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-stimulated HaCaT cells and anti-dinitrophenyl immunoglobulin E (DNP-IgE)- and human serum albumin (HSA)-stimulated RBL-2H3 cells were used to investigate the levels of inflammatory factors and their mechanisms. AD-like lesions were induced by applying DNCB/DFE to mice. The effect of UDCA administration in AD-like mice was analyzed by assessing organ weight, serum IgE and inflammatory cytokine levels, and histopathological changes using immunohistochemical and immunofluorescent staining.
KEY FINDINGS
In HaCaT cells, UDCA significantly diminished TARC, MDC, MCP-1, and IL-6 expression by inhibiting the phosphorylation of nuclear NF-κB and cytoplasmic IκB, and also increased the levels of skin barrier protein. In RBL-2H3 cells, UDCA reduced β-hexosaminidase and IL-4 levels. In AD-like mice, UDCA suppressed organ hypertrophy, ear edema, SCORAD index, DFE-specific IgE levels, inflammatory cytokine levels, skin hypertrophy, mast cell invasion, skin barrier loss, and thymic stromal lymphopoietin-positive areas.
SIGNIFICANCE
UDCA suppressed the expression of pro-inflammatory cytokines by keratinocytes and mast cells. It also alleviated atopy by suppressing symptoms without organ toxicity in AD-like mice. UDCA may be an effective and safe treatment for AD.
Topics: Humans; Animals; Mice; Rats; Dermatitis, Atopic; Skin; Dinitrochlorobenzene; Ursodeoxycholic Acid; Cytokines; NF-kappa B; Immunoglobulin E; Hypertrophy; Mice, Inbred BALB C
PubMed: 38490296
DOI: 10.1016/j.lfs.2024.122560 -
Journal of Medicinal Chemistry Mar 2024Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as...
Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4--dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from with moderate potency against PDE4 (IC = 3.26 ± 0.28 μM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of that showed high inhibitory potency on PDE4 (IC = 0.17 ± 0.02 μM), good anti-TNF-α activity (EC = 0.19 ± 0.10 μM), remarkable selectivity profile, and good skin permeability. The topical treatment of resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.
Topics: Mice; Animals; Dermatitis, Atopic; Phosphodiesterase 4 Inhibitors; Dinitrochlorobenzene; Lignans; Tumor Necrosis Factor Inhibitors; Cytokines; Skin
PubMed: 38489246
DOI: 10.1021/acs.jmedchem.3c02424