Animal Model Of Atopic Dermatitis Research Articles

Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin.

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells. K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

Improved Anti-Inflammatory Effects of Liposomal Astaxanthin on a Phthalic Anhydride-Induced Atopic Dermatitis Model.

Previously, we found that astaxanthin (AST) elicited an anti-inflammatory response in an experimental atopic dermatitis (AD) model. However, the use of AST was limited because of low bioavailability and solubility. We hypothesized that liposome formulation of AST could improve this. In this study, we compared the anti-inflammatory and anti-dermatotic effects of liposomal AST (L-AST) and free AST. We evaluated the effect of L-AST on a phthalic anhydride (PA)-induced animal model of AD by analyzing morphological and histopathological changes. We measured the mRNA levels of AD-related cytokines in skin tissue and immunoglobulin E concentrations in the serum. Oxidative stress and transcriptional activities of signal transducer and activator of transcription 3 (STAT3) and nuclear factor (NF)-κB were analyzed via western blotting and enzyme-linked immunosorbent assay. PA-induced dermatitis severity, epidermal thickening, and infiltration of mast cells in skin tissues were ameliorated by L-AST treatment. L-AST suppressed AD-related inflammatory mediators and the inflammation markers, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in PA-induced skin conditions. Oxidative stress and expression of antioxidant proteins, glutathione peroxidase-1 (GPx-1) and heme oxygenase-1 (HO-1), were recovered by L-AST treatment in skin tissues from PA-induced mice. L-AST treatment reduced transcriptional activity of STAT3 and NF-κB in PA-induced skin tissues. Our results indicate that L-AST could be more effective than free AST for AD therapy.

Anti-ORAI1 antibody DS-2741a, a specific CRAC channel blocker, shows ideal therapeutic profiles for allergic disease via suppression of aberrant T-cell and mast cell activation.

ORAI1 constitutes the pore‐forming subunit of the calcium release‐activated calcium (CRAC) channel, which is responsible for store‐operated calcium entry into lymphocytes. It is known that ORAI1 is essential for the activation of T cells and mast cells and is considered to be a potent therapeutic target for autoimmune and allergic diseases. Here, we obtained a new humanized antibody, DS‐2741a, that inhibits ORAI1 function. DS‐2741a bound to human‐ORAI1 with high affinity and without cross‐reactivity to rodent Orai1. DS‐2741a demonstrated suppression of CRAC‐mediated human and mouse T‐cell activation and mast cell degranulation in human ORAI1 knock‐in mice. Furthermore, DS‐2741a ameliorated house dust mite antigen‐induced dermatitis in the human ORAI1 knock‐in mouse. Taken together, DS‐2741a inhibited T‐cell and mast cell functions, thus improving skin inflammation in animal models of atopic dermatitis and reinforcing the need for investigation of DS‐2741a for the treatment of allergic diseases in a clinical setting.

A Comparative Study of Levocetirizine Loaded Vesicular and Matrix Type System for Topical Application: Appraisal of Therapeutic Potential against Atopic Dermatitis

Topical drug delivery offers improved therapeutic effect and reduced systemic adverse effects of the administered compounds. The present work was aimed at developing and comparing levocetirizine loaded polymeric nanoparticles and niosomal formulation(s), respectively, against dinitrochlorobenzene-induced atopic dermatitis animal model. The niosome and chitosan nanoparticle were developed and evaluated for particle size distribution, drug loading, and entrapment efficiency. The formulations were optimized through Box-Behnken design. The optimized formulations were dispersed in carbopol gel and evaluated for ex vivo permeation, retention, and in vivo studies. The optimized niosomes and chitosan nanoparticle exhibited a particle size range of 384.4 ± 64.3 nm and 382.7 ± 59.2 nm, drug loading of 18.99 ± 0.02% and 12.2 ± 1.6%, and entrapment efficiency of 46.63 ± 2.12% and 29.6 ± 1.6%, respectively. The permeation and retention studies displayed less permeation and significantly (p < 0.01) high retention percentage of LCZD by OPT-N gel when compared with OPT-CN gel. In in vivo studies revealed that OPT-N significantly (p < 0.05) reduces erythema score (from 3 to 1) and scratching frequency (70–25 scratches/20 min). OPT-N gel shows high entrapment efficiency and skin retention capacity of the drug along with better topical applicability and higher therapeutic efficacy. The OPT-N also manifested the maximum peripheral action of LCZD against AD as compared with optimized chitosan gel and plain LCZD gel.

Effect of Lactobacillus helveticus HY7801 Oral Administration on Immune Response and Skin Improvement in Animal Model of Atopic Dermatitis

Effect of Lactobacillus helveticus HY7801 Oral Administration on Immune Response and Skin Improvement in Animal Model of Atopic Dermatitis

The Role of Circadian Clock Period 2 (per 2) gene and the expression of per2 related gene in atopic dermatitis animal model

Abstract Atopic dermatitis is a chronic, inflammatory skin disorder associated with defective skin barrier and epidermal hyper reactivity. AD is a Th2 mediated allergic disease. GATA3 is a transcription factor that plays an important role in Th2 differentiation. In this study we investigated the per2 gene role and the expression of per2 related genes in atopic dermatitis. We established the atopic dermatitis animal model in per2 knock out and C57BL/6 by 2,4-dinitrochlorobenzene (DNCB). A subset of mice in both per2 knock out and C57BL/6 were treated with saline as control group. The skin lesions severity score was alleviated in per2 knock out mice DNCB group than wild type group. We examined the TNF-α mRNA expression in skin samples that showed that per2 knock out mice protected from DNCB induced inflammation than wild type mice. We next examined BMAL1 mRNA expression in skin samples that showed BMAL1 functioned as anti-inflammatory molecule in per2 knock out mice and levels are high than wild type mice and GATA3 expression levels were not initiated in per2 knock out mice than wild type mice. According to these results we hypothesized per2 knock out mice protected from allergic atopic dermatitis by increasing anti-inflammatory molecule BMAL1 through supressing GATA3.

Comparison of the presentation of atopic dermatitis induced by trinitrochlorobenzene and house dust mite in NC/Nga mice.

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease. To understand AD, there have been many trials establishing AD animal models. Although various trials to establish AD animal models have been existed, even the mechanisms of AD in animal models are not enough clarified.ObjectivesThis study assessed AD characteristics induced in Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice following trinitrochlorobenzene (TNCB) treatment for different periods and house dust mite (HDM) treatment to compare each model's immunological patterns, especially with cytokine antibody array tool.MethodsIn this study, we exposed Nc/Nga mice to TNCB or HDM extract to induce AD. Nc/Nga mice were divided into 4 groups: control, TNCB 2 weeks-treated, TNCB 8 weeks-treated, and HDM-treated groups. After AD induction, all mice were evaluated by serum immunoglobulin E (IgE) concentration and serum cytokine antibody assays, scoring of skin lesions, scoring of scratching frequency, and histological analysis.ResultsThe results showed significant differences between groups in serum IgE concentration, skin lesion scores, and scratching frequency. The analysis results for serum cytokine antibody arrays showed that in the TNCB 8 weeks- and HDM-treated groups, but not in the TNCB 2 weeks-treated group, expressions of genes related to the immune response were enriched. Among the histological results, the skin lesions in the HDM-treated group were most similar to those of AD.ConclusionsWe confirmed that immunological pattern of AD mice was markedly different between HDM and TNCB treated groups. In addition, the immunological pattern was quietly different dependent on TNCB treated duration.

Anti-inflammatory effect of bee venom in phthalic anhydride-induced atopic dermatitis animal model

Globally, many people have been affected with atopic dermatitis (AD), a chronic inflammatory skin disease. AD is associated with multiple factors such as genetic, inflammatory, and immune factors. Bee venom (BV) is now widely used for the treatment of several inflammatory diseases. However, its effect on 5% phthalic anhydride (PA)-induced AD has not been reported yet. We investigated the anti-inflammatory and anti-AD effects of BV in a PA-induced animal model of AD. Balb/c mice were treated with topical application of 5% PA to the dorsal skin and ears for induction of AD. After 24h, BV was applied on the back and ear skin of the mice three times a week for 4weeks. BV treatment significantly reduced the PA-induced AD clinical score, back and ear epidermal thickness, as well as IgE level and infiltration of immune cells in the skin tissues compared to those of control mice. The levels of inflammatory cytokines in the serum were significantly decreased in BV-treated group compared to PA-treated group. In addition, BV inhibited the expression of iNOS and COX-2 as well as the activation of mitogen-activated protein kinase (MAPK) and NF-ҡB induced by PA in the skin tissues. We also found that BV abrogated the lipopolysaccharide or TNF-α/IFN-γ-induced NO production, expression of iNOS and COX-2, as well as MAPK and NF-ҡB signaling pathway in RAW 264.7 and HaCaT cells. These results suggest that BV may be a potential therapeutic macromolecule for the treatment of AD.

MicroRNA‑146a as a potential regulator involved in the pathogenesis of atopic dermatitis.

Previous studies have demonstrated that microRNA (miR)-146a is involved in the inflammatory response of atopic dermatitis (AD). The aim of the present study was to investigate the expression of miR-146a in the serum of patients with AD and in skin lesions of AD animal models. In addition, we aimed to predict and verify the target genes of miR-146a. miR-146a expression was measured in AD patient serum via reverse transcription-quantitative PCR. T-helper (Th)1 [CD4+; interferon (IFN)-γ+] and Th2 [CD4+; interleukin (IL)-4+] expression in peripheral blood mononuclear cells was evaluated using flow cytometry. Following the establishment of a 2,4-dinitrofluorobenzene-induced C57BL/6 mouse AD model, Th1 (CD4+IFN-γ+) and Th2 (CD4+IL-4+) expression was analyzed in murine spleen cells via flow cytometry. Plasmids were transfected into 293T cells and at 48 h post-transfection, cells were analyzed using a luciferase assay system. The results revealed that the AD group had a significantly lower Th1/Th2 ratio and a significantly higher miR-146a expression compared with the control group (P<0.05). Furthermore, a decreased Th1/Th2 ratio and a significantly increased miR-146a expression were observed in the model group compared with the control group (P<0.01). We also conducted a dual-luciferase assay to determine whether small ubiquitin-related modifier 1 (SUMO1) if the target gene of miR-146a. We observed a ~30% decrease in the relative luciferase activity in cells containing the 3′-untranslated region of SUMO1 + miR-146a). The results of the luciferase assay indicated that may be a direct mRNA target of miR-146a; however, the quantification of band density of SUMO1 expression following western blotting did not significantly differ. The development of animal models in AD research is of vital importance. The results revealed that miR-146a may be a potential regulator involved in the pathogenesis of AD. Furthermore, the current study determined that miR-146a could be a valuable marker of AD and thus, may be applied in the development of therapeutic strategies for treating AD.

341 IL-4Rα Targeted-POLIGOTM Cream Improves DNCB-Induced Atopic Dermatitis Mouse Model

Atopic dermatitis (AD) is the most common type of eczema. The Th2 immune response seems to play a pivotal role in AD. This involves in Th2 cytokines such as IL-4 which share the IL-4Rα. Transdermal administration improves patient quality of life because of noninvasive; however, typical ASO and antibody drug delivery into the skin can be challenging owing to the barrier of tight junctions in the granular layer. Therefore, we aimed to develop a delivery system of ASO for topical application using our technology, POLIGOTM. POLIGOTM, which is based on PNA (Peptide Nucleic Acid) has the nanoparticle characters and is able to transdermal delivery without physical force (microneedle). We improved the PNA (high selectivity, stability, nanoparticle-characters) to overcome low selectivity and delivery using our technology. Our purpose was to evaluate the effects of POL201 (cream type of IL-4Rα targeted POLIGOTM) on dinitrochlorobenzene (DNCB) induced NC/Nga mice. We measured epidermis thickness, CD3, and CD11c expression of DNCB-induced AD mouse skin and the levels of IgE, IL-4, IL-13, and TARC in the serum by ELISA. Also, the effects of POL201 on expression level of IL-4Rα was evaluated in AD mouse skin. POL201 efficiently decreased the number of CD3/CD11c positive cells as well as thickness of the epidermis and dermis. The POL201 group significantly reduced serum level of IgE, IL-4, IL-13 and TARC. Moreover, IL-4Rα inhibited in the POL201 group compared with the DNCB-treated group. In addition, POL201 group showed that the clinical index, SCORAD (redness, scabs, itching and thickness) was dramatically improved than positive control (dexamethasone group). As the results, POL201 significantly inhibited AD pathogenesis and clinical index through reduction of IL-4Rα expression in AD animal model. Unlike conventional ASO treatments (subcutaneous injection), POL201 was able to deliver to the skin using cream formulation alone and inhibited the target gene IL-4Rα. Our results suggest that POL201 could be a potential therapeutic candidate for the treatment of AD.

Extracts of the leaves of Pyrus ussuriensis Maxim. Alleviate itch sensation via TSLP-dependent manner in mouse models of atopic dermatitis

Pyrus ussuriensis Maxim. commonly known as “Sandolbae” in Korean is a pear tree widely distributed across East Asia. Recent studies indicate that P. ussuriensis Maxim. leaves (PUL) have antipruritic effects. This study aimed to determine the effects of PUL extract and its fractions in decreasing the itch sensation and skin lesions in two distinct animal models of atopic dermatitis (AD) induced by dinitrofluorobenzene (DNFB) or house dust mite (HDM). Our results showed that the total ethanol extract of PUL decreased the scratching behavior in mice with DNFB- and HDM-induced AD. Moreover, the ethyl acetate fraction of PUL significantly improved the overall condition of the mice with AD induced by HDM. Further, we used HEK293T cells that express receptors and ion channels for thymic stromal lymphopoietin (TSLP), a potent pruritogen for AD, to determine the mechanisms underlying the antipruritic effects of PUL extract/fractions. Specific subfractions of the PUL strongly inhibited the increase in calcium levels induced by TSLP. In addition, the specific subfraction of PUL inhibited the TSLP-induced increase in calcium levels in cultured mouse dorsal root ganglia neurons. Thus, our results showed that the PUL extract could be effective for alleviating pruritus, and the antipruritic effects were exerted probably via the inhibition of the TSLP pathway in peripheral sensory neurons governing the itch sensation in AD.

Anti‑inflammatory effects of Dendropanaxmorbifera in lipopolysaccharide‑stimulated RAW264.7 macrophages and in an animal model of atopic dermatitis.

Dendropanax morbifera (D. morbifera), known as Dendro, means ‘omnipotent drug’ (Panax), and has been called the panacea tree. Various studies on D. morbifera are currently ongoing, aiming to determine its medicinal uses. The present study investigated the anti-inflammatory effects and underlying mechanism of a natural extract of D. morbifera leaves (DPL) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In the present study, the following assays and models were used: MTT assay, nitric oxide (NO) assay, western blotting, ELISA and mouse models of atopic dermatitis. DPL extract markedly reduced the production of NO, inducible NO synthase and interleukin-6, as well as the nuclear translocation of nuclear factor-κB (NF-κB). Additionally, the LPS-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2), P38 and c-Jun N-terminal kinase (JNK) was suppressed by DPL extract. Taken together, these results indicate that NF-κB, ERK1/2, P38 and JNK may be potential molecular targets of DPL extract in the LPS-induced inflammatory response. Subsequently, the present study investigated the effects of DPL extract in a 2,4-dinitrochlorobenzene-induced atopic dermatitis mouse model. Ear thickness, serum immunoglobulin E levels and histological analysis revealed that the DPL extract was effective in attenuating the inflammatory response. These results indicate that DPL extract has anti-inflammatory potential and may be developed as a botanical drug to treat atopic dermatitis.

Effect of Yupingfeng granules on the skin barrier in atopic dermatitis mice models

OBJECTIVETo investigate effect of Yupingfeng granules, prepared with Chinese Medicines, on the wound healing and on the expression of aquaporin 3 (AQP3) and the skin barrier in the animal models of atopic dermatitis (AD). METHODSAcute skin lesions of AD models were prepared using 2,4-dinitrochlorobenzo (DNCB) in mice and animals were treated with either Yupingfeng granules or placebo for two weeks. Skin wound healing outcome was assessed by measuring skin thickness, weight (quality) of the skin, and trans-epidermal water loss (TEWL). Expression of AQP3 mRNA and protein was assessed by reverse transcriotion polymerase chain reaction (RT-PCR) and immunoblotting, respectively. RESULTSYupingfeng granule treatment resulted in significant acceleration of wound healing with 63.64% efficiency, which was significantly higher than that of placebo granule treatment (31.82%, P < 0.01 by Wilcoxon Rank-sum test). Skin thickness, weight of the wounded skin, and TEWL were significantly higher in the AD models compared to that of normal animals. Treatment with Yupingfeng granules resulted in significant decrease in skin thickness [(937 ±31) vs (360 ±21) urn, P < 0.01], weight of the wounded skin [(42 ± 4) vs (24 ± 5) mg, P < 0.01], and TEWL [(30 ±4) vs (13 ± 4) g • h−1 • m−2, P < 0.01]. Yupingfeng granules also significantly down-regulated mRNA and protein expression of AQP3 in the animal models. CONCLUSIONOur findings suggested that Yupingfeng granules could be used in AD treatment.

Immunomodulatory effect of thymoquinone on atopic dermatitis

BackgroundAtopic dermatitis (AD) or atopic eczema is a skin disease characterized with itching, increased serum level of immunoglobulin E, and peripheral eosinophilia. Thymoquinone (TQ) is an important ingredient of Nigella sativa seeds having antioxidant and anti-inflammatory effects. ObjectivePresent study investigates the immunomodulatory effects of Thymoquinone (TQ) in mice model of atopic dermatitis. MethodsEar pinnas of mice were sensitized and challenged with DNCB (2–4 di nitro chloro benzene) to induce AD-like lesions. The mice were then treated with TQ and tacrolimus, both orally and topically. Ear thickness and weight were measured along with gross changes. Total and differential leukocyte counts were measured in blood. Total serum IgE levels were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of IL-4, IL-5, and IFN-γ in ear tissue were measured using reverse transcription polymerase chain reaction (RT-PCR). ResultsBoth oral and topical thymoquinone showed the potential to improve atopic dermatitis by significantly reducing the inflammatory cells infiltration in the blood (p < 0.001) and improving the dermatitis score (p < 0.001). Significant reduction in ear thickness (p < 0.001) and IgE levels (p < 0.001) were also observed. TQ and tacrolimus also significantly attenuated mRNA expression levels of IL-4, IL-5 and IFN-γ (p < 0.001). Conclusions & clinical relevanceTaken together, our results showed that oral and topical application of thymoquinone exerts immunomodulatory effects in animal model of atopic dermatitis, suggesting further studies and clinical trials to establish it as a candidate nutraceutical for the treatment of AD.

1035 Loss of transcription factor Ovol1 enhances skin inflammation in animal models of atopic dermatitis and psoriasis

1035 Loss of transcription factor Ovol1 enhances skin inflammation in animal models of atopic dermatitis and psoriasis

Anti-inflammatory effect of astaxanthin in phthalic anhydride-induced atopic dermatitis animal model.

In this study, we investigated anti-dermatitic effects of astaxanthin (AST) in phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. AD-like lesion was induced by the topical application of 5% PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100μL of 1mg/mL and 2mg/mL of AST (10μg or 20μg/cm2 ) was spread on the dorsum of ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) activity. We also measured tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and immunoglobulin E (IgE) concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). AST treatment attenuated the development of PA-induced AD. Histological analysis showed that AST inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. AST treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as release of TNF-α, IL-1β, IL-6 and IgE. In addition, AST (5, 10 and 20μM) potently inhibited lipopolysaccharide (LPS) (1μg/mL)-induced nitric oxide (NO) production, expression of iNOS and COX-2 and NF-κB DNA binding activities in RAW 264.7 macrophage cells. Our data demonstrated that AST could be a promising agent for AD by inhibition of NF-κB signalling.

Histopathologic Features in Animal Model of Atopic Dermatitis Induced by Topical Application of Oxazolone

Animal models of atopic dermatitis (AD) are widely used to investigate therapeutic effects of candidates for AD. However, the characteristics of each model are not fully understood. This study was designed to compare the animal models of dermatitis induced by dinitrofluorobenzene (DNFB) and oxazolone (Ox). We investigated the effects of DNFB and Ox on skin thicknesses and weights as well as skin lesions associated with AD such as scale, crust and erythematous eruption, and histopathological changes such as hyperkeratosis, dermal and epidermal hyperplasia and immune cell infiltration in inflamed tissues. Multiple application of 0.5% Ox onto the skin increased skin thickness and weight compared to those of DNFB treated mice, as well as those of normal mice. In addition, topical application of DNFB induced marked scale, crust and erythematous eruption, while Ox induced erythematous eruption and mild scale and crust. Histopathological examination revealed that 0.5% Ox induced marked hyperplasia in the dermis and epidermis, large vesicles, spongiotic changes, mild hyperkeratosis and immune cell infiltration in balb/c mice. These data suggest that multiple applications of Ox can induce chronic AD like dermatitis in balb/c mice.

The Use of Therapeutic Nanoparticulate Systems for Treating Atopic Dermatitis

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving defects in epidermal barrier function and abnormal immune response to environmental stimuli. Standard treatment of AD involves topical application of emollients and anti-inflammatory drugs such as corticosteroids. Objective: Because of the barrier function defects in AD skin, the topical drug delivery can lead to systemic drug absorption, thereby eliciting systemic complications. Nanoparticles as the carriers used for cutaneous drug delivery provide some benefits over conventional formulations, including enhanced stability, improved epithelium permeability and bioavailability, controlled drug release, skin targeting, and minimal side effects. In recent years, the concept of using nanocarriers as vehicles for drug delivery to manage AD has attracted increasing attention. Polymeric nanoparticles, lipid nanoparticles, and liposomes are the most extensively studied nanocarriers for the treatment of AD. In this review, we highlight the recent progress on the development of nanosystems for AD treatment. Method: We systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for AD treatment. Different AD animal models for evaluating the efficacy of the therapeutic nanoparticles are described herein. Results: The discrepancy of the nanoparticle skin absorption between healthy skin and AD skin is also discussed. Conclusion: This review aimed to summarize the evidence for the therapeutic advantages of nanoparticles over the conventional AD therapy.

Anti‑inflammatory effect of quercetin and galangin in LPS‑stimulated RAW264.7 macrophages and DNCB‑induced atopic dermatitis animal models.

Flavonols are compounds that have been shown to possess potent anti-inflammatory effects in cellular and animal models of inflammation. In the present study, the anti-inflammatory effects and mechanisms of two natural flavonols, quercetin and galangin, in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were investigated. It was identified that quercetin and galangin markedly reduced the production of nitric oxide (NO), inducible NO synthase and interleukin-6, and the nuclear translocation of nuclear factor-κB (NF-κB). In addition, LPS-induced activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun N-terminal kinase (JNK) was suppressed by quercetin and galangin. Taken together, these data implied that NF-κB, Erk1/2 and JNK may be potential molecular targets of quercetin and galangin in an LPS-induced inflammatory response. Subsequently, the effects of oral administration of quercetin or galangin, either alone or in combination, in a 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD) mouse model were investigated. As a result, measurements of ear thickness and the levels of serum immunoglobulin E, and histological analysis revealed that the two flavonols led to a decrease in inflammation, whereas, in combination, they were even more effective. These results suggested that quercetin and galangin may be promising therapeutic agents for AD. Additionally, their combination may be a novel therapeutic strategy for the prevention of AD.

The AHR as a therapeutic target for inflammatory skin diseases

To investigate effect of Yupingfeng granules, prepared with Chinese Medicines, on the wound healing and on the expression of aquaporin 3 (AQP3) and the skin barrier in the animal models of atopic dermatitis (AD).Acute skin lesions of AD models were prepared using 2,4-dinitrochlorobenzo (DNCB) in mice and animals were treated with either Yupingfeng granules or placebo for two weeks. Skin wound healing outcome was assessed by measuring skin thickness, weight (quality) of the skin, and trans-epidermal water loss (TEWL). Expression of AQP3 mRNA and protein was assessed by reverse transcriotion polymerase chain reaction (RT-PCR) and immunoblotting, respectively.Yupingfeng granule treatment resulted in significant acceleration of wound healing with 63.64% efficiency, which was significantly higher than that of placebo granule treatment (31.82%, P < 0.01 by Wilcoxon Rank-sum test). Skin thickness, weight of the wounded skin, and TEWL were significantly higher in the AD models compared to that of normal animals. Treatment with Yupingfeng granules resulted in significant decrease in skin thickness [(937 ±31) vs (360 ±21) urn, P < 0.01], weight of the wounded skin [(42 ± 4) vs (24 ± 5) mg, P < 0.01], and TEWL [(30 ±4) vs (13 ± 4) g • h−1 • m−2, P < 0.01]. Yupingfeng granules also significantly down-regulated mRNA and protein expression of AQP3 in the animal models.Our findings suggested that Yupingfeng granules could be used in AD treatment.