Atopic Skin Research Articles

Attenuation of 1-chloro-2,4-dinitrobenzene-induced inflammation in atopic dermatitis-like skin lesions in rats by a pyrrole containing FELL-NH 2 bioconjugate: Cannabinoid receptor type 1 involvement

Atopic dermatitis (AD) is a chronic inflammatory skin condition of significant health and social importance, which justifies the search for new means of treatment. Since the endogenous cannabinoid system appears to be involved in the pathogenesis of AD, the proposed article summarizes the clinical impact on skin inflammation in a rat model of 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis-like condition after exogenous systemic administration of the cannabinoid receptor type 1 (CB1r) agonist anandamide, as well as after local treatment with a newly synthesized pyrrole moiety containing bioconjugate of FELL tetrapeptide with CB1r-dependent analgesic activity. The changes in skin lesions and ear thickness were estimated along with the CB1r expression immunohistochemically determined on skin punch biopsies. The results showed attenuation of skin lesions by anandamide and lack of positive effect after introduction of CB1r antagonist, accompanied by a change in CB1r expression, suggesting the involvement of the cannabinoid system in the defensive functions of the skin. The topically applied newly synthesized bioconjugate also favorably affected skin manifestations of inflammation, but without a change in CB1r expression, suggesting the involvement of other mechanisms in the reported effects.

Honey Phytochemicals: Bioactive Agents With Therapeutic Potential for Dermatological Disorders.

Honey has been reported to have a range of biological activities including antimicrobial, immunomodulatory, and wound healing effects. Indeed, medical-grade honey is currently used in hospitals for the clinical management of wound infections. Honey is also of scientific interest for its therapeutic effects on other dermatological disorders such as atopic dermatitis, rosacea, and skin cancer. Recent studies have uncovered that honey contains a range of phytochemicals including flavonoids, dicarboxylic acids, coumarins, and phenolic acids. In this review, PubMed was used to search the scientific literature on the biological properties of honey phytochemicals in relation to dermatological disorders and to evaluate their potential as bioactive agents, drugs, or cosmeceuticals for the treatment of skin disease. The review revealed that phytochemicals found in honey have antimicrobial, anti-inflammatory, antiaging, antioxidant, anticancer, depigmenting, photoprotective, wound healing, and skin barrier enhancing properties. Although further high-quality studies are required to establish clinical efficacy, these findings suggest that honey phytochemicals may have the potential to be used as bioactive agents for the management of a range of dermatological disorders including wounds, psoriasis, atopic dermatitis, vitiligo, rosacea, and skin cancer.

Pinewood VOC emissions protect from oxazolone-induced inflammation and dysbiosis in a mouse model of atopic dermatitis

Pinewood, increasingly used in construction and interior fittings, emits high amounts of volatile organic compounds (VOCs), which tend to accumulate in indoor air. Whether indoor VOCs affect the development of atopic dermatitis (AD) is a matter of debate. We aimed to evaluate the effects of pinewood VOCs on the development of AD-like inflammatory phenotype and linked microbiome alterations, both hallmarks of AD. An oxazolone-induced mouse model of AD was exposed to three different VOC concentrations emitted by pinewood plates throughout the experiment. The disease course and associated immunological and microbiological changes were evaluated. To validate and translate our results to humans, human keratinocytes were exposed to a synthetic pinewood VOCs mixture in an AD environment. Pinewood emitted mainly terpenes, which at a total concentration of 5 mg/m3 significantly improved oxazolone-induced key AD parameters, such as serum total IgE, transepidermal water loss, barrier gene alteration, inflammation, and dysbiosis. Notably, exposure to pinewood VOCs restored the loss of microbial richness and inhibit Staphylococci expansion characteristic of the oxazolone-induced mouse AD model. Most beneficial effects of pinewood VOCs were dose-dependent. In fact, lower (<3 mg/m3) or higher (>10 mg/m3) pinewood VOC levels maintained only limited beneficial effects, such as preserving the microbiome richness or impeding Staphylococci expansion, respectively. In the human in-vitro model, exposure of keratinocytes grown in an AD environment to a pinewood VOCs mixture reduced the release of inflammatory markers. In conclusion, our results indicate that airborne phytochemicals emitted from pinewood have beneficial effects on an AD-like phenotype and associated dysbiosis. These investigations highlight the effects of terpenes as environmental compounds in the prevention and/or control of atopic skin disease.

Enoximone alleviates atopic dermatitis-like skin inflammation via inhibition of type 2 T helper cell development

Atopic dermatitis (AD) is an inflammatory skin disease that affects approximately 15–20 % of the children and 1–3 % of the adults worldwide. Corticosteroids and calcineurin inhibitors are used in AD therapy; however, they cause various side effects. Current studies focus on novel therapeutic targets such as phosphodiesterases (PDEs) to mitigate AD. However, the relationship between PDE3 inhibitors and AD has not yet been reported. This study aimed to investigate the therapeutic effects and pharmaceutical mechanisms of enoximone (Enox), a PDE3 inhibitor. Mice were stimulated with 2,4-dinitrochlorobenzene (DNCB) to induce AD-like skin inflammation and were topically treated with Enox for 2 weeks. Treatment with Enox reduced the dermatitis score, skin water loss, IgE production, and expression of cytokines and chemokines that were elevated by DNCB. Histologically, Enox treatment reduced the skin thickness and the infiltration of various inflammatory cells, including macrophages, mast cells, eosinophils, and type 2 T helper (Th2) cells. HuT78, a human T cell line, was used to investigate the differentiation of T cells into Th2 cells. Enox treatment decreased the expression of Th2 cytokines and GATA3, a Th2 cell marker in HuT78, and suppressed signaling pathways that play a crucial role in Th2 cell differentiation. Collectively, the results demonstrate that Enox alleviates AD-like skin inflammation by inhibiting T-cell development. Thus, Enox may be a therapeutic candidate for the treatment of AD.

Particulate Matter and Its Molecular Effects on Skin: Implications for Various Skin Diseases.

Particulate matter (PM) is a harmful air pollutant composed of chemicals and metals which affects human health by penetrating both the respiratory system and skin, causing oxidative stress and inflammation. This review investigates the association between PM and skin disease, focusing on the underlying molecular mechanisms and specific disease pathways involved. Studies have shown that PM exposure is positively associated with skin diseases such as atopic dermatitis, psoriasis, acne, and skin aging. PM-induced oxidative stress damages lipids, proteins, and DNA, impairing cellular functions and triggering inflammatory responses through pathways like aryl hydrocarbon receptor (AhR), NF-κB, and MAPK. This leads to increased production of inflammatory cytokines and exacerbates skin conditions. PM exposure exacerbates AD by triggering inflammation and barrier disruption. It disrupts keratinocyte differentiation and increases pro-inflammatory cytokines in psoriasis. In acne, it increases sebum production and inflammatory biomarkers. It accelerates skin aging by degrading ECM proteins and increasing MMP-1 and COX2. In conclusion, PM compromises skin health by penetrating skin barriers, inducing oxidative stress and inflammation through mechanisms like ROS generation and activation of key pathways, leading to cellular damage, apoptosis, and autophagy. This highlights the need for protective measures and targeted treatments to mitigate PM-induced skin damage.

51248 Safety and Tolerance Evaluation of a Suncare Product in Ethically Diverse Children with Atopic Dermatitis-Prone Skin

51248 Safety and Tolerance Evaluation of a Suncare Product in Ethically Diverse Children with Atopic Dermatitis-Prone Skin

49450 3-Dimensional tissue clearing and quantification of epidermal innervation in pruritic atopic dermatitis skin

49450 3-Dimensional tissue clearing and quantification of epidermal innervation in pruritic atopic dermatitis skin

Effects of a pH-Regulating Emollient Cream in Mild Atopic Dermatitis Patients with Moderate Localized Lesions

Introduction: Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin. Methods: The assessment for local severity of AD was done with the Scoring Atopic Dermatitis Index (SCORAD) and skin dryness was assessed by capacitance measurement. Results: The results showed that the test product lowered skin pH and improved AD skin lesions from moderate to mild during 2 weeks of application. In the treated area a lowered pH of about 0.85 units was found. Together with the lowering of pH, the local SCORAD significantly improved from 8.3 on average down to 4.0, while in the untreated area, only a slight improvement (from 8.2 to 6.4) was found. Conclusion: Synergistic effects of the test product’s pH lowering and emollient properties might explain the observed improvements in clinical signs of AD and further research against a comparator would allow the specific contribution of pH modulation to these improvements to be unambiguously isolated.

The role of dendritic cells in the instruction of helper T cells in the allergic march.

Allergy is a complex array of diseases influenced by innate and adaptive immunity, genetic polymorphisms, and environmental triggers. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier defects and immune dysregulation, sometimes leading to asthma and food allergies because of the atopic march. During atopic skin inflammation, Langerhans cells and dendritic cells (DCs) in the skin capture and deliver allergen information to local lymph nodes. DCs are essential immune sensors coordinating immune reactions by capturing and presenting antigens to T cells. In the context of allergic responses, DCs play a crucial role in instructing two types of helper T cells - type 2 helper T (Th2) cells and follicular helper T (TFH) cells - in allergic responses and IgE antibody responses. In skin sensitization, the differentiation and function of Th2 cells and TFH cells are influenced by skin-derived factors, including epithelial cytokines, chemokines, and signaling pathways to modify the function of migratory DCs and conventional DCs. In this review, we aim to understand the specific mechanisms involving DCs in allergic responses to provide insights into the pathogenesis of allergic diseases and potential therapeutic strategies.

Overexpression of the β-Subunit of Acid Ceramidase in the Epidermis of Mice Provokes Atopic Dermatitis-like Skin Symptoms.

We previously reported that a pathogenic abnormality in the barrier and water-holding functions of the stratum corneum (SC) in the skin of patients with atopic dermatitis (AD) is mainly attributable to significantly decreased levels of total ceramides in the SC. That decrease is mediated by the abnormal expression of a novel ceramide-reducing enzyme, sphingomyelin/glucosylceramide deacylase (SGDase), which is the β-subunit (ASAH1b) of acid ceramidase. In this study, we determined whether mice overexpressing ASAH1b in their epidermis develop AD-like skin symptoms. We generated transgenic (TG) mice overexpressing ASAH1b, regulated by the involucrin promoter, to localize its expression in the upper epidermis. After hair removal using a depilatory cream containing glycolic acid, the TG mice without any visible skin inflammation at 8 weeks of age had increased levels of ASAH1b and decreased levels of SC ceramide, with disrupted barrier functions measured by trans-epidermal water loss compared to the wild-type (WT) mice. Interestingly, enzymatic assays revealed that SGDase activity was not detectable in the skin of the TG mice compared to WT mice. Immunological staining revealed that there was an increased expression level of IL-33 in the epidermis and an accumulation of macrophages in the dermis of TG mice compared to WT mice, which are phenotypic characteristics of AD, that were exacerbated by tape-stripping of the skin. In the skin of the TG mice, the mRNA levels of IL-5, CCL11, IL-22, CXCL10, and IFNγ were significantly upregulated compared to the WT mice, and tape-stripping significantly increased the mRNA levels of IL-4, IL-33, CXCL1, CXCL12, TLR9, and CD163 compared to WT mice. These findings strongly indicate that the skin of the depilatory cream-treated TG mice exists in an atopic dry skin condition that is highly sensitive to various environmental stimuli. The sum of our results suggests that ASAH1b itself, even in the absence of its enzymatic activity, is a major etiologic factor for atopic dry skin symptoms via an unknown mechanism.

The Usefulness of Line-Field Confocal Optical Coherence Tomography in Monitoring Epidermal Changes in Atopic Dermatitis in Response to Treatment: A Pilot Study.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Due to its high prevalence, considerable morbidity, and chronicity, there is a need for the accurate in vivo evaluation of treatment efficacy. Line-field confocal optical coherence tomography (LC-OCT) is a new emerging imaging technique able to perform a non-invasive, real-time examination of the epidermis and the upper dermis. LC-OCT may represent a promising tool in the diagnosis and treatment follow-up of chronic eczematous skin diseases with barrier defects. We aimed to investigate the role of LC-OCT in the non-invasive monitoring of the treatment effect on five patients with severe atopic dermatitis during dupilumab treatment. LC-OCT imaging was performed on five patients (three women and two men) aged between 14 and 85 years old at the baseline and at 2, 4, and 6 weeks of treatment with dupilumab. The LC-OCT scans were performed at two sites, the lesional skin in the antecubital fossa and the extensor part of the arm, considered a control site on each patient for comparison. The captured images were later evaluated. Descriptive statistics and a t-test were used to compare the analyzed parameters over time and between involved atopic skin and clinically healthy skin. The LC-OCT imaging was able to detect the difference in stratum corneum (SC) thickness and quality and epidermal thickness (ET) and the changes before and after treatment with high accuracy. The main findings include a significant reduction in the epidermal and stratum corneum thickness and decreased epidermal spongiosis and inflammation, with better quality of the stratum corneum indicating restoration of its tightness at both lesional and control sites. This study demonstrates that clinical improvement of affected and unaffected atopic skin under dupilumab treatment correlates with the LC-OCT findings. LC-OCT represents a novel, non-invasive tool examining the in vivo skin barrier and inflammation and can help to monitor the treatment efficacy among patients with atopic dermatitis in daily practice.

Topical calcineurin and mammalian target of rapamycin inhibitors in inflammatory dermatoses: Current challenges and nanotechnology‑based prospects (Review).

Topical therapy remains a critical component in the management of immune‑mediated inflammatory dermatoses such as psoriasis and atopic dermatitis. In this field, macrolactam immunomodulators, including calcineurin and mammalian target of rapamycin inhibitors, can offer steroid‑free therapeutic alternatives. Despite their potential for skin‑selective treatment compared with topical corticosteroids, the physicochemical properties of these compounds, such as high lipophilicity and large molecular size, do not meet the criteria for efficient penetration into the skin, especially with conventional topical vehicles. Thus, more sophisticated approaches are needed to address the pharmacokinetic limitations of traditional formulations. In this regard, interest has increasingly focused on nanoparticulate systems to optimize penetration kinetics and enhance the efficacy and safety of topical calcineurin and mTOR inhibitors in inflamed skin. Several types of nanovectors have been explored as topical carriers to deliver tacrolimus in both psoriatic and atopic skin, while preclinical data on nanocarrier‑based delivery of topical sirolimus in inflamed skin are also emerging. Given the promising preliminary outcomes and the complexities of drug delivery across inflamed skin, further research is required to translate these nanotherapeutics into clinical settings for inflammatory skin diseases. The present review outlined the dermatokinetic profiles of topical calcineurin and mTOR inhibitors, particularly tacrolimus, pimecrolimus and sirolimus, focusing on their penetration kinetics in psoriatic and atopic skin. It also summarizes the potential anti‑inflammatory benefits of topical sirolimus and explores novel preclinical studies investigating dermally applied nanovehicles to evaluate and optimize the skin delivery, efficacy and safety of these 'hard‑to‑formulate' macromolecules in the context of psoriasis and atopic dermatitis.

Effect of Th2 cytokines on ceramide subclasses based on a model of reconstructed human epidermis.

Atopic dermatitis (AD) is associated with chronic inflammation and an altered skin barrier. Lipids of the stratum corneum of AD patients are known to differ substantially in composition from those of healthy subjects. A reconstructed human epidermis (RHE) model has been developed in vitro in order to mimic the characteristics of AD. In this study, using this model, we compared lipid profile modifications between control RHE and RHE treated with Th2 cytokines in order to mimic AD. We focused particularly on the lipid profile of the ceramide subclasses: non-hydroxy sphingosine (NS) and esterified ω-hydroxy sphingosine (EOS), which have been reported to be clearly modified in atopic skin. RHE lipids were extracted and analysed using high-performance liquid chromatography coupled to high-resolution mass spectrometry. The following lipid profile changes were observed in Th2-cytokine-treated RHE: (i) an increase in ceramide NS composed of an unsaturated fatty acid chain; (ii) an increase in saturated ceramide NS with small total carbon content (≤40 carbon atoms), whereas NS with a higher total carbon content (≥42 carbon atoms) was decreased; and (iii) a decrease in ceramide EOS. These results are in accordance with reported lipid profiles of human atopic skin in vivo. Moreover, the in vitro model represents a useful tool to better understand the pathogenesis of AD which may be used for future screening of new effective treatments.

Safety and Tolerance Evaluation of a Suncare Product in Ethnically Diverse Children With Atopic Dermatitis-Prone Skin

Atopic Dermatitis (AD) is a common chronic inflammatory skin condition, with high prevalence in children. Sun protection is important for children with eczema and AD-prone skin, yet many sunscreens can cause skin irritation due to their formulations. In this study, we evaluated the safety and tolerance of an SPF 50 sunscreen in ethnically diverse children with a history of AD over 4 weeks of product use. A total of 45 children from diverse racial/ethnic backgrounds, aged 3 to 12 years old with skin phototypes I-VI, plus a history of eczema and perceived sensitive skin completed the study. All participants applied sunscreen daily on the face and body, at least 15 minutes prior to sun exposure and as needed. After 4 weeks, evaluations were performed by a dermatologist and by participants for tolerability. Product performance questionnaires were also completed by parents/guardians of pediatric participants. After 4 weeks of sunscreen application, tolerability assessments of skin dryness, peeling, erythema, and edema were all absent in children participants. Parent/guardian evaluations of sunscreen tolerability for their child also revealed no perceived skin issues. These results were consistent with no adverse event being observed throughout the study. Parents/guardians reported that sunscreen application on children was smooth and even, with the absence of a white cast appearance on children with skin of color. We conclude from this study that this SPF 50 sunscreen is safe to use in ethnically diverse children with a history of AD and sensitive skin. J Drugs Dermatol. 2024;23(8):669-673.&nbsp; doi:10.36849/JDD.8282.

Oral and topical administration of a geranyl acetophenone attenuates DNCB-induced atopic dermatitis-like skin lesions in BALB/c mice

Atopic dermatitis (AD) is a chronic, allergic inflammatory skin disorder that lacks a definite cure. Using a mouse DNCB-induced AD-like skin lesions model, this study evaluated the potential therapeutic utility of tHGA as an oral and topical treatment for AD. Male BALB/c mice were sensitised and challenged with 1% and 0.5% DNCB on their shaved dorsal skin. Mice in the treatment group were administered tHGA (20, 40, and 80 mg/kg) orally three times per week for 2 weeks, or tHGA (0.2%, 1%, and 5%) topically once daily for 12 days. On day 34, the mice were euthanized, and blood and dorsal skin samples were obtained for analysis. All doses of orally and topically administered tHGA significantly improved scratching, epidermal thickness, blood eosinophilia and mast cell infiltration. There was a minor discrepancy between the two routes of administration, with orally treated tHGA showing significant reductions in Scoring of Atopic Dermatitis (SCORAD), tissue eosinophil infiltration, serum IgE and skin IL-4 levels with treatment of 40 and 80 mg/kg tHGA, whereas topically applied tHGA showed significant reductions in all dosages. These findings suggest that tHGA exhibited therapeutic potential for AD as both oral and topical treatment ameliorates AD-like symptoms in the murine model.

Papain Suppresses Atopic Skin Inflammation through Anti-Inflammatory Activities Using In Vitro and In Vivo Models.

Papain (PN) is a proteolytic enzyme derived from Carica Papaya L. While the pharmacological effects of PN have not been extensively studied compared to its enzymatic activity, PN also holds potential benefits beyond protein digestion. This study aimed to investigate the potential effects of PN against skin inflammation in house dust mite Dermatophagoides farinae body (Dfb)-exposed NC/Nga atopic dermatitis (AD) mice and human HaCaT keratinocytes and their underlying mechanisms. The effects of PN on the skin were assessed via histological examination, measurements of transepidermal water loss (TEWL), quantitative reverse transcription-polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Our findings indicated that the oral intake of PN decreased the severity scores of lesions resembling AD, TEWL, and the levels of inflammatory cytokines and serum immunoglobulin E in Dfb-induced AD mice, along with a reduction in epidermal thickness and mast cell infiltration. Additionally, PN inhibited the activation of the mitogen-activated protein kinases (MAPKs) and the signal transducer and activator of transcription (STAT) pathways in Dfb-induced AD mice and HaCaT keratinocytes. Moreover, PN improved survival and reduced ROS production in H2O2-damaged HaCaT keratinocytes and enhanced the expression of antioxidant enzymes in Dfb-induced AD mice. Concludingly, the oral administration of PN suppressed inflammatory mediators and downregulated the MAPKs/STAT pathway, suggesting its potential role in AD pathogenesis.

Tapinarof Cream 1% Once Daily is Efficacious for the Treatment of Atopic Dermatitis in Patients with Skin of Color Down to 2 Years of Age in Two Pivotal Phase 3 Trials

Introduction: Patients with atopic dermatitis (AD) and skin of color can have heterogeneous presentations and treatment responses. In the pivotal phase 3 ADORING 1 and 2 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) was significantly efficacious and well tolerated versus vehicle in adults and children down to 2 years of age with AD. Objective: Here, we report analyses of efficacy by skin color in ADORING 1 and 2, based on patients’ self-identified race and investigator-assessed Fitzpatrick skin type. Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic DermatitisTM (vIGA-ADTM) score of ≥3, an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were randomized 2:1 to tapinarof cream or vehicle QD for 8 weeks. The primary efficacy endpoint was a vIGA-ADTM score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline at Week 8. Secondary endpoints included proportion of patients with a ≥75% improvement in Eczema Area and Severity Index (EASI75). Results: Of the 407 and 406 randomized patients, 8.8–15.3% were Asian, 26.5–35.0% were Black, 44.8–56.8% were White, and 2.7–5.2% were Other groups (American Indian or Alaska Native, Native Hawaiian or Pacific Islander, or multiple races) across trials. Patients with Fitzpatrick skin types IV, V, and VI represented 23.8–25.1%, 20.6–22.2%, and 7.6–8.9%, respectively, of patients (&gt;50% in both trials). Across trials, vIGA-ADTM responses (ranges) for tapinarof versus vehicle were: Asian, 39.5–48.9% vs 3.7–18.5%; Black, 43.1–47.0% vs 17.5–24.1%; White, 49.4–52.1% vs 12.2–14.5%; and Other, 26.0–44.8% vs 0.0–40.2%. EASI75 responses for tapinarof versus vehicle were: Asian, 47.6–76.6% vs 17.7–20.2%; Black, 48.9–55.3% vs 25.7–30.0%; White, 61.4–67.8% vs 19.6–20.7%; and Other, 38.3–63.3% vs 0.0–40.6%. Similarly, high and consistent vIGA-ADTM and EASI75 responses were reported with tapinarof versus vehicle in patients with Fitzpatrick skin types I–III and IV–VI. Conclusion: Tapinarof cream 1% QD was consistently efficacious among all racial groups and Fitzpatrick skin types in adults and children down to 2 years of age with AD, including patients with skin of color, who were highly represented in these trials.

Cholesterol Nanofiber Patches with Sustainable Oil Delivery Eliminate Inflammation in Atopic Skin.

Atopic skin is dry and itchy and lacks integrity. Impaired skin barrier results from altered lipid composition of the skin. A crucial skin lipid, cholesterol, provides flexibility and homeostasis of the cell membranes' lipid bilayer. Cholesterol-based creams and natural oils, especially blackcurrant seed oil, are beneficial for skin care as they hydrate the skin and improve its integrity. The major atopic symptom, skin dryness, can be overcome by the application of porous patches enhanced with cholesterol and natural oil. The base of the patches is constructed of polyimide (PI) nanofibers with cholesterol coatings and externally added blackcurrant seed oil. The presence of cholesterol in PI mats hinders the passage of oil through the patches to the skin, resulting in sustained and prolonged skin hydration. The theoretical and numerical investigations of oil dynamics in porous mats confirmed the experimental results, showing a prolonged skin hydration effect up to 6 h. Additionally, as demonstrated by in vivo tests on atopic mice, cholesterol patches lower serum immunoglobulin E levels and expression of proinflammatory cytokines in the skin, thereby accelerating skin healing. Our results hold great promise for the long-term application of the patches in atopic dermatitis treatment.

Vinpocetine, a phosphodiesterase 1 inhibitor, mitigates atopic dermatitis-like skin inflammation.

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.

Disrupting TSLP–TSLP receptor interactions via putative small molecule inhibitors yields a novel and efficient treatment option for atopic diseases

Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP inhibitors exist due to the challenges of disrupting the protein–protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokines at low micromolar concentrations. For in-depth analysis, we developed a human atopic disease drug discovery platform using multi-organ chips. Here, topical application of BP79 onto atopic skin models that were co-cultivated with lung models and Th2 cells effectively suppressed immune cell infiltration and IL-13, IL-4, TSLP, and periostin secretion, while upregulating skin barrier proteins. RNA-Seq analysis corroborate these findings and indicate protective downstream effects on the lungs. To the best of our knowledge, this represents the first report of a potent putative small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases.