Atopic Dermatitis-like Symptoms Research Articles

Evodiamine Alleviates 2,4-Dinitro-1-Chloro-Benzene-Induced Atopic Dermatitis-like Symptoms in BALB/c Mice.

Evodiamine is an alkaloid found in Evodia fruits, a traditional Chinese medicine. Preclinical studies have demonstrated its anti-inflammatory and neuroprotective properties. The 2,4-dinitro-1-chloro-benzene (DNCB) was used to test the effects of evodiamine on a chemically induced atopic dermatitis-like model in BALB/c mice. Evodiamine significantly lowered serum immunoglobulin E levels, which increased as an immune response to the long-term application of DNCB. Several atopic dermatitis-like skin symptoms induced by DNCB, including skin thickening and mast cell accumulation, were suppressed by evodiamine therapy. DNCB induced higher levels of pro-inflammatory cytokines in type 2 helper T (Th2) cells (IL-4 and IL-13), Th1 cells (IFN-γ and IL-12A), Th17 cells (IL-17A), Th22 cells (IL-22), and chemokines (IL-6 and IL-8). These increases were suppressed in the lymph nodes and skin following evodiamine treatment. The results of our study indicate that evodiamine suppresses atopic dermatitis-like responses in mice and may therefore be useful in treating these conditions.

Atopic dermatitis in early life and pain at 10years of age: An exploratory study.

Pain is a distinctive burden in atopic dermatitis and recognized as an important and highly prevalent symptom. It is unknown if the presence of atopic disease may sensitize children to adverse pain profiles in the long term. We aimed to assess the impact of early-life atopic dermatitis-like symptoms on pain at 10years of age. We used data from 1302 and 874 participants of the Generation XXI birth cohort evaluated at 6 and 15months, respectively, and 10years. Atopy-like symptoms since birth, including atopic dermatitis, were collected at ages 6 and 15months by interviewing parents. Pain history in the last 3months at age 10 was collected from parents and children using structured questionnaires. We computed relative risks (RR) and respective 95% confidence intervals of pain features at age 10 according to each atopic-like symptom at 6 and 15months. Children whose parents reported atopic dermatitis-like symptoms at 6months and at 15months had higher risk of reporting any pain (RR 1.75 [1.15-2.66]) and multisite pain, respectively (RR 1.67 [1.18-2.37]) at 10years of age. Conclusion: Atopic dermatitis symptoms in early life were associated with a higher risk of pain at age 10, suggesting that potential for sensitization during the first decade of life and highlighting the importance of improving the health care of children with atopic dermatitis is worth investigating. What is Known: • Atopic disorders have been associated with many non-atopic comorbidities, including chronic pain. • Pain and atopic dermatitis share common inflammatory pathways. Inflammation, injury to the skin from scratching, fissures, and intolerance to irritants related to atopic dermatitis can cause pain. What is New: • Atopic dermatitis in early life is linked to an increased likelihood of experiencing pain at the age of 10, which suggests that exploring the potential for sensitization is a worthwhile area of investigation. • Our proof-of-concept study highlights the potential benefit of studying management targets and improving itching and relieving skin pain as quickly as possible, avoiding potential long-term consequences of the sensitization process.

Evodiae Fructus extract suppresses inflammatory response in HaCaT cells and improves house dust mite-induced atopic dermatitis in NC/Nga mice

This study was conducted to assess the effect of Evodiae Fructus 70% ethanol extract (EFE) on the pathology of atopic dermatitis using in vitro and in vivo models. The major compounds in EFE were identified by ultra-performance liquid chromatography with tandem mass spectrometry as rutaecarpine, evodiamine, evodol, dehydroevodiamine, limonin, synephrine, evocarpine, dihydroevocarpine, and hydroxyevodiamine. EFE significantly decreased chemokine levels in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In house dust mite-treated NC/Nga mice, topical application of EFE significantly decreased the dermatitis score, epidermal hyperplasia and thickening, mast cell infiltration, and plasma levels of histamine and corticosterone. Thymic stromal lymphopoietin, CD4+ T cells, interleukin-4, and intercellular adhesion molecule-1 expression in the lesioned skin was reduced in the treated mice. The mechanism of EFE was elucidated using transcriptome analysis, followed by experimental validation using Western blotting in HaCaT cells. EFE down-regulated the activation of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in HaCaT cells. EFE improves atopic dermatitis-like symptoms by suppressing inflammatory mediators, cytokines, and chemokines by regulating the JAK-STAT and MAPK signaling pathways, suggesting its use as a potential agent for the treatment of atopic dermatitis.

Ameliorative Efficacy of Combined Betel and Tea Tree Essential Oil-Incorporated Cream on DNCB-Induced Atopic Dermatitis-like Symptoms in BALB/c Mice

Aims: This study aimed to investigate the ameliorative efficacy of combined betel and tea tree essential oil-incorporated cream on DNCB-induced atopic dermatitis-like symptoms in BALB/c mice.
 Methodology: cream formulation containing blended betel essential oil (1%) and tea tree essential oil (0.5%) was topically applied onto the dorsal skin of 2,4-dinitrochlorobenzene-sensitized BALB/c mice once a day during four weeks of assay. Phosphate-Buffered Saline (PBS) and protopic (tacrolimus 0.1%) were used as negative and positive control, respectively. All mice were subjected to the assessment of AD-like symptoms including the severity of skin lesions, frequency of scratching behavior and histological features.
 Results: The blended essential oil-incorporated cream has significant effect against DNCB-induced eczematous skin lesions in BALB/c mice with the dermatitis score of 2.17 ± 0.75 (n = 6, p < 0.05) and the number of scratching behavior of 6.09 ± 1.28 (n = 6, p < 0.05) compared to negative control (7.00 ± 0.63 and 18.55 ± 1.23, n = 6, p < 0.05, respectively). Animals treated showed dose-related improvements in the histology of the skin.
 Conclusion: These findings confirmed the ameliorative efficacy of betel and tea tree essential oil-incorporated cream on DNCB-induced atopic dermatitis like symptoms in BALB/c mice. However, further studies are necessary to elucidate the possible synergistic effect of blended essential oils from betel and tea tree as well as the interplaying roles of major molecules present in essential oils.

Ursolic acid ameliorates DNCB-induced atopic dermatitis-like symptoms in mice by regulating TLR4/NF-κB and Nrf2/HO-1 signaling pathways.

Ursolic acid (UA) is a triterpenoid compound found in natural plants. It has been reported to have anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in atopic dermatitis (AD) is unknown. This study aimed to evaluate the therapeutic effect of UA in AD mice and explore the underlying mechanisms. Balb/c mice were treated with 2, 4-dinitrochlorobenzene (DNCB) to induce AD-like lesions. During modeling and medication administration, dermatitis scores and ear thickness were measured. Subsequently, histopathological changes, levels of T helper cytokines, and oxidative stress markers levels were evaluated. Immunohistochemistry staining was used to assess changes in the expression of the nuclear factor of kappa B (NF-κB) and NF erythroid 2-related factor 2 (Nrf2). Furthermore, CCK8 assay, reactive oxygen species (ROS) assay, real-time PCR, and western blotting were employed to evaluate the effects of UA on ROS levels, inflammatory mediator production, and the NF-κB and Nrf2 pathways in TNF-α/IFN-γ-stimulated HaCaT cells. The results showed that UA significantly reduced dermatitis score and ear thickness, effectively inhibited skin proliferation and mast cell infiltration in AD mice, and decreased the expression level of T helper cytokines. Meanwhile, UA improved oxidative stress in AD mice by regulating lipid peroxidation and increasing the activity of antioxidant enzymes. In addition, UA inhibited ROS accumulation and chemokine secretion in TNF-α/IFN-γ-stimulated HaCaT cells. It might exert anti-dermatitis effects by inhibiting the TLR4/NF-κB pathway and activating the Nrf2/HO-1 pathway. Taken together, our results suggest that UA may have potential therapeutic effects on AD and could be further studied as a promising drug for AD treatment.

A New Moisturiser Improves DNCB-induced Atopic Dermatitis-like Symptoms and Restores Skin Barrier Function in BALB/c Mice.

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder with eczematous and pruritic lesions. Topical moisturisers and either topical corticosteroids or calcineurin inhibitors are usually recommended. Restoring the skin barrier function alleviates AD symptoms. To evaluate the efficacy of a new moisturiser compared to commercially available products in an AD murine model. Experimental AD was induced with topical applications of 2,4-DiNitroChloroBenzene (DNCB) on the shaved back skin of BALB/c mice from Day 1 to Day 38. Mice were randomized to either Vehicle/-, DNCB/-, or DNCB/Eczekalm (test product), DNCB/Atopiclair®, or DNCB/Lipikar (reference products) groups. Once daily application of either Eczekalm or Atopiclair® or Lipikar on the AD lesion was performed from Day 32 to Day 38. The AD severity index (ADSI) and animal behaviour were monitored throughout the study. The trans-epidermal water loss (TEWL) was measured on the sacrifice day (Day 39). At Day39, ADSI in the DNCB/Eczekalm, DNCB/Lipikar, and DNCB/Atopiclair® groups were significantly lower by -70%, -68%, and -57%, respectively, as compared to DNCB/- (p < 0.001). No sign of erythema was observed in the DNCB/Eczekalm group. Mean scores of skin oedema, excoriation, and dryness in the DNCB/Eczekalm, DNCB/Lipikar, and DNCB/Atopiclair® groups were significantly lower than in the DNCB/-. No significant difference was observed between DNCB/Eczekalm and DNCB/Lipikar groups. Mean TEWL in DNCB/Eczekalm group was significantly lower than the ones of DNCB/Atopiclair® (-43%, p < 0.001) and DNCB/Lipikar (-15%, p < 0.05). Eczekalm treatment significantly reduced the inflammatory effects due to AD and itching episodes and restored the skin barrier function.

Moringa concanensis L. Alleviates DNCB-Induced Atopic Dermatitis-like Symptoms by Inhibiting NLRP3 Inflammasome-Mediated IL-1β in BALB/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, dry skin and redness on the face and inside elbows or knees. Most patients with AD are children and youths, but it can also develop in adults. In the therapeutic aspect, treatment with corticosteroids for AD has several side effects, such as weight loss, atrophy and acne. In the current study, we examined the anti-inflammatory effect of Moringa concanensis leaves on HaCaT keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like symptoms in BALB/c mice. We observed that M. concanensis treatment exhibited significant inhibition in the production of inflammatory mediators and proinflammatory cytokines, such as IL-1β, in LPS-induced HaCaT keratinocytes by downregulating the NLRP3 inflammasome activation. Moreover, M. concanensis inhibited the activation of JNK, AP-1 and p65, which resulted in the deformation of NLRP3 in LPS-stimulated HaCaT cells. In mice with DNCB-induced AD-like skin lesions, the administration of M. concanensis ameliorated the clinical symptoms, such as the dermatitis score, thickness of lesional ear skin and TEWL. Furthermore, M. concanensis could attenuate the activation of the immune system, such as reducing the spleen index, concentration of the IgE levels and expression of the NLRP3 inflammasome in ear tissues. Therefore, our results suggest that M. concanensis exerts anti-atopic dermatitis effects by inhibiting the NLRP3 inflammasome-mediated IL-1β.

Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway

Background and purposeAtopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus and impaired skin barrier function. The pathology of AD involves in immune dysfunction and epidermal barrier disruption. Reactive oxygen species (ROS) are found to be associated with AD, and play a role in the immunological abnormalities and dysfunctional skin barrier. Nicotinamide mononucleotide (NMN) plays an important role in oxidative stress related diseases, but its role in AD is unclear. MethodsKM mice were treated with DNFB to induce AD-like lesion and typical applied with NMN for two weeks. The dermatitis score, the degree of itching and TEWL were evaluated during modeling. Epidermal thickness of skin lesions and histopathological changes were detected. Further, inflammatory factors, epidermal differentiation-related genes, oxidative stress indicators and JAK2/STAT5 signaling pathway were evaluated. NHEK cells were stimulated by TNF-α/IFN-γ after pre-treatment with NMN, then ROS levels, inflammatory factors and JAK2/STAT5 signaling pathway were detected. ResultsNMN exhibited potent anti-atopic activities, shown by alleviated AD-like symptoms, inhibited the increased expression of inflammatory cytokines and restored proteins and mRNA level of skin barrier genes. In addition, NMN inhibited TNF-α/IFN-γ-stimulated elevation of inflammatory chemokines, which was associated with blocking the activation of ROS-mediated JAK2/STAT5 pathway. ConclusionNMN may have a positive effect on relieving symptoms of AD.

Dietary scallop oil prepared from the internal organs of Japanese giant scallop (Patinopecten yessoensis) improved mite allergen-induced atopic dermatitis-like symptoms on the dorsal skin of NC/Nga mice.

This study aimed to investigate the effects of scallop oil (SCO) on atopic dermatitis (AD)-like symptoms induced by mite allergens in the dorsal and ear skins of NC/Nga mice compared to those of refined corn oil and krill oil (KO). SCO, rich in n-3 polyunsaturated fatty acids and phospholipids, was prepared from the internal organs of Japanese giant scallop, an underutilized fishery resource in Japan. Results showed that SCO intake improved AD-like symptoms, including ear edema, ear thickness, and transepidermal water loss of dorsal skin, and tended to decrease the scratching behavior, whereas KO intake did not. Further, SCO intake decreased the degranulated mast cell count and increased the tight junction protein claudin-1 expression, which is important for the barrier function, in the dorsal skin compared to refined corn oil intake. SCO improved the AD-like symptoms by suppressing mast cell degranulation and strengthening the barrier function of dorsal skin in NC/Nga mice.

Tea saponin extracted from seed pomace of Camellia oleifera Abel ameliorates DNCB-induced atopic dermatitis-like symptoms in BALB/c mice

Tea saponin (TS) has antibacterial and anti-inflammatory properties. However, the antipruritic and anti-inflammatory effects on atopic dermatitis (AD) are unknown. This study, therefore, evaluated the therapeutic effects of TS from seed pomace of C. oleifera on AD in 2,4-Dinitrochlorobenzene (DNCB)-caused BALB/c mice. The major compositions were separated and analyzed by ultrahigh-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry. The antipruritic efficacy as well as the anti-inflammatory activity of TS were assessed using skin lesions, scratching tendency, and cytokine levels in DNCB-caused BALB/c mice. Twenty-six TS were preliminarily identified, and the dermatitis results revealed that TS could significantly reduce the degree of dermatitis and scratching in AD mice induced by DNCB. TS also normalized the skin barriers and inhibited the generation of inflammatory cytokines in the serum and skin tissue of mice. Overall, TS possesses antipruritic and anti-inflammatory properties, making it a potential natural resource for dermatitis treatment.

Inhibitory effect of α-cubebenoate on atopic dermatitis-like symptoms by regulating Th2/Th1/Th17 balance in vivo

Ethnopharmacological relevanceBakumijiogan (Kampo herbal formulation) and Kangqian decoction (Chinese herbal medicine formulation) have been used for the treatment of atopic dermatitis (AD) like symptoms. Schisandra chinensis Baill (Family: Magnoliaceae) is a component of both formulations. Its extracts showed inhibition of AD. Aim of the studyWe aimed to elucidate an active phytochemical from Schisandra chinensis and evaluated its effects on AD-like symptoms. Materials and methodsWe fractionated a component from Schisandra chinensis by chasing inhibitory activity on mast cell degranulation. We identified α-cubebenoate as an active phytochemical and investigated its effects by using an in vivo 1-chloro-2,4-dinitrobenzene (CDNB)-induced AD model in BALB/c mice. Resultsα-Cubebenoate significantly decreased CDNB-induced skin hypertrophy and accumulation of mast cells in the epidermis and dermis. Increases in pro-inflammatory chemokine and cytokine levels in the skin, lymph node size, and immunoglobulin E levels in the serum were significantly ameliorated by α-cubebenoate. Conclusionα-Cubebenoate regulates dermal immune responses by suppressing the Th2/Th17/Th1 immune balances, resulting in amelioration of AD-like symptoms and suppression of immune response in lymph nodes. Thereby, this study provides evidence for its therapeutic efficacy in the treatment of AD symptoms.

Orobol from enzyme biotransformation attenuates Dermatophagoides farinae-induced atopic dermatitis-like symptoms in NC/Nga mice.

Orobol, a metabolite of genistein, is rare in natural soybean. Several studies have revealed the immune-controlling effects of orobol on inflammatory diseases. Furthermore, a few studies have demonstrated that orobol decreases pro-inflammatory compounds resulting in the alleviation of allergic reactions. However, the relationship between orobol and atopic dermatitis (AD) in animal models has not been revealed. Therefore, we sought to investigate the effects of orobol on AD-like symptoms. AD-like symptoms and skin lesions were induced by repeated topical application of Dermatophagoides farinae extract (DFE) on the skin of NC/Nga mice. Topical application of orobol attenuated DFE-induced AD-like symptoms and transepidermal water loss and increased skin hydration. Histopathological analysis revealed that orobol alleviated DFE-induced eosinophil and mast cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers including serum TARC, MDC, and IgE. In addition, orobol alleviated dorsal Th2 cytokines such as IL-4 and IL-13. Pre-treatment of orobol decreased the activity of the MAPKs and NF-κB signalling cascade in the TNFα/IFNγ-induced HaCaT cell line. These results suggest that orobol, a natural dietary isoflavone, has therapeutic efficacy for the prevention and treatment of AD.

Topical Application of Galgeunhwanggeumhwangryeon-Tang Recovers Skin-Lipid Barrier and Ameliorates Inflammation via Filaggrin-Thymic Stromal Lymphopoietin-Interleukin 4 Pathway.

Background and objectives: The purpose of this study was to confirm the effect of Galgeunhwanggeumhwangryeon-tang (GGRT) on the skin barrier integrity and inflammation in an atopic dermatitis-like animal model. Materials and Methods: The model was established using lipid barrier elimination (LBE) in BALB/c mice. Ceramide 3B, a control drug, and GGRT were applied to the skin of LBE mice. Gross observation and histological examination were combined with measurement of skin score, trans-epidermal water loss, and pH. The expression of filaggrin, kallikrein-related peptidase 7 (KLK7), protease-activated receptor-2 (PAR-2), thymic stromal lymphopoietin (TSLP), and interleukin 4 (IL-4) was examined. Results: The effect of GGRT on atopic dermatitis was estimated in silico using two individual gene sets of human atopic dermatitis. In animal experiments, GGRT treatment reduced atopic dermatitis-like symptoms, as confirmed via gross and histological observations, skin score, pH change, and trans-epidermal water loss. The expression level of filaggrin increased in the skin of GGRT-treated mice compared to that in the LBE group. The expression levels of KLK7, PAR2, TSLP, and IL-4 were decreased in GGRT-treated mice skin compared to those in LBE mice. Conclusions: We demonstrated that GGRT restored the skin barrier and reduced inflammatory reactions in a murine model of atopic dermatitis.

Fe2+: Fe3+ Molar Ratio Influences the Immunomodulatory Properties of Maghemite (γ-Fe2O3) Nanoparticles in an Atopic Dermatitis Model.

Here, we report the different antioxidant and physiological effects of maghemite nanoparticles (γ-Fe2O3 NPs) obtained using various Fe2+: Fe3+ molar ratios (FM1 = 1: 1, FM2 = 1: 2, and FM3 = 2: 3) via coprecipitation from ferrous/ferric salts. We investigated the physical, optical, and antioxidant properties of FM1, FM2, and FM3 nanoparticles by conducting UV, Raman, FTIR, and EDX spectroscopic analyses along with DPPH radical scavenging activity. Results showed the highest DPPH scavenging activity in the FM2 group (50.76%), while the activity in the FM1 and FM3 groups was 23.60% and 34.63%, respectively. In addition, topical application of nanoparticles induced significant but different anti-inflammatory and immunomodulatory effects in Dermatophagoides farinae extract/2,4-dinitrochlorobenzene (DFE/DNCB)-sensitized BALB/c mice. The FM2 treatment alleviates more effectively the DFE/DNCB-induced atopic dermatitis-like (AD-like) symptoms in mouse ears (edema, excoriation, scaling, and hemorrhage). In comparison with the DFE/DNCB-sensitized mice, FM2 treatment greatly reduced the size and weight of the spleen and the lymph nodes. It also suppressed mast cell infiltration (2-fold) and reduced dermal and epidermal thickness in mice. In addition, FM2 treatment exhibited better inhibition of the mRNA levels of Th1 (IFN-γ and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, and IL-31), as well as the levels of various inflammation-related proteins (COX-2, iNOS, and TNF-α). Moreover, we demonstrated that an increasing proportion of Fe3+ in Fe2+: Fe3+ enhances the antioxidant activity and increases the anti-inflammatory and immunomodulatory effects of γ-Fe2O3 NPs in an AD mouse model. Thus, γ-Fe2O3 NPs could be used in the formulation of nonsteroidal drugs for AD treatment.

Acacia Polyphenol Ameliorates Atopic Dermatitis in Trimellitic Anhydride-Induced Model Mice via Changes in the Gut Microbiota.

We have previously shown that acacia polyphenol (AP), which was extracted from the bark of Acacia mearnsii De Wild, exerts antiobesity, antidiabetic, and antihypertensive effects. In this study, we examined the effect of AP on atopic dermatitis. Trimellitic anhydride (TMA) was applied to the ears of mice to create model mice with atopic dermatitis. The frequency of scratching behavior in the TMA-treated group was significantly higher than that in the control group, and the expression levels of inflammatory markers (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2) in the skin also increased. In contrast, both the frequency of scratching behavior and the expression levels of skin inflammatory markers in the AP-treated group were significantly lower than those in the TMA-treated group. The abundances of beneficial bacteria, such as Bifidobacterium spp. and Lactobacillus spp., increased in the AP-treated group compared with the TMA-treated group. Furthermore, the abundances of Bacteroides fragilis and Clostridium coccoides in the gut, which are known for anti-inflammatory properties, increased significantly with AP administration. The present results revealed that AP inhibits TMA-induced atopic dermatitis-like symptoms. In addition, the results also suggested that this effect may be associated with the mechanism of gut microbiota improvement.

Piperine Ameliorates Trimellitic Anhydride-Induced Atopic Dermatitis-Like Symptoms by Suppressing Th2-Mediated Immune Responses via Inhibition of STAT6 Phosphorylation.

Atopic dermatitis (AD) is a common inflammatory skin disease predominately related to Type 2 helper T (Th2) immune responses. In this study, we investigated whether piperine is able to improve AD symptoms using a trimellitic anhydride (TMA)-induced AD-like mouse model. Topical treatment with piperine reduced ear swelling (ear thickness and epidermal thickness) induced by TMA exposure. Furthermore, piperine inhibited pro-inflammatory cytokines such as TNF-α and IL-1β in mouse ears, compared with the TMA-induced AD group. In measuring allergic immune responses in draining lymph nodes (dLNs), we found that IL-4 secretion, GATA3 mRNA level, and STAT6 phosphorylation were suppressed by piperine treatment. In an ex vivo study, piperine also inhibited the phosphorylation of STAT6 on the CD4+ T cells isolated from splenocytes of BALB/c mice, and piperine suppressed IL-4-induced CCL26 mRNA expression and STAT6 phosphorylation in human keratinocytes resulting in the inhibition of infiltration of CCR3+ cells into inflammatory lesions. These results demonstrate that piperine could ameliorate AD symptoms through suppression of Th2-mediated immune responses, including the STAT6/GATA3/IL-4 signaling pathway. Therefore, we suggest that piperine is an excellent candidate as an inhibitor of STAT6 and may help to improve AD symptoms.

Ferulic acid alleviates atopic dermatitis-like symptoms in mice via its potent anti-inflammatory effect

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the interactions between multiple genetic and environmental factors. The pathogenesis of AD is still not completely clear. Steroid topical therapy has severe side effects for chronic AD symptoms and new therapeutic options are urgently needed. Ferulic acid (FA) is a novel natural dietary polyphenol with anti-oxidative and anti-inflammatory effects.Methods: FA was assessed in BALB/c mice with AD-like lesions resulted from repetitive applications of 2,4-dinitrochlorobenzene (DNCB). Molecular and serological properties of the AD lesions as well as the overall symptomatic score were evaluated.Results: FA ameliorated the overall symptoms of AD, including the severity of skin lesion and incidence of scratching behavior. Systemically, FA markedly decreased DNCB-induced Th2 cytokines and IgE in the peripheral blood. In the local tissue with AD lesions, FA suppressed DNCB-stimulated mRNA production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and IL-31. In THP-1 cells, a human monocyte model, FA dose-dependently suppressed DNCB-elicited up-regulation of CD54 and CD86 at cell surface, secretion of pro-inflammatory cytokines IL-6 and TNF-α, and NFκB signaling activation.Conclusion: Our findings demonstrated that FA could serve as a promising therapeutic agent in AD treatment.

Enzyme-treated date plum leave extract ameliorates atopic dermatitis-like skin lesion in hairless mice

Objective: To evaluate the effect of different extracts of Diospyros lotus leaves in atopic dermatitis Methods: Diospyros lotus leaves were extracted in ethanol and treated with or without hydrochloric acid or α-rhamnosidase to obtain three different extracts-ethanol, acid-hydrolyzed, and enzyme-hydrolyzed leaf extracts of date plum. The myricitrin content in all samples was measured using HPLC analysis. In vitro antioxidant and anti-inflammatory activities of the extracts were determined by measuring DPPH radical scavenging activities and nitric oxide production in RAW264.7 cells, respectively. Seven- week-old male hairless mice were used to evaluate the anti-atopic dermatitis effects of three extracts in vivo. Splenocytes and mast cells were used to further determine the anti-atopic dermatitis effects of the major compound in the ethanol leaf extract. Results: Enzyme-hydrolyzed leaf extract showed significant in vitro antioxidant and anti-inflammatory activities, and attenuated atopic dermatitis-like skin symptoms and clinical signs more significantly than ethanol and acid-hydrolyzed leaf extracts in 1-fluoro-2,4- dinitrobenzene and house dust mite antigen-treated hairless mice. Enzyme-hydrolyzed leaf extract also suppressed the serum level of immunoglobulin E, interleukin (IL)-4, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, thymic stromal lymphopoietin, and thymus and activation-regulated chemokine in mice with atopic dermatitis. Furthermore, histological analysis revealed that enzyme- hydrolyzed leaf extract suppressed the increased epidermal thickness, dermal infiltration of inflammatory cells, and infiltration and degranulation of mast cells more markedly than the other two extracts in atopic dermatitis-like skin lesions. In addition, this extract effectively inhibited the production of IFN-γ, IL-4,and thymus and activation-regulated chemokine compared with the other two extracts in concanavalin A-stimulated splenocytes. Myricitrin, a major compound of enzyme-hydrolyzed leaf extract, suppressed atopic dermatitis biomarkers in stimulated mouse splenocytes and HMC-1 human mast cells. Conclusions: These results suggest that enzyme-hydrolyzed leaf extract might be a potential candidate to treat atopic dermatitis.

Topical Application of 7,3',4'-Trihydroxyisoflavone Alleviates Atopic Dermatitis-Like Symptoms in NC/Nga Mice.

Atopic dermatitis is a skin disease characterized by chronic inflammatory lesions, and new therapies are needed to address its rising prevalence. Soy isoflavone has been highlighted as a potential new cosmeceutical material that may have applications in atopic dermatitis care. We have developed a technique to attach an additional -OH group to the ortho position of -OH in the phenol ring using a special enzyme. By adding the -OH group to daidzein, 7,3',4'-trihydroxyisoflavone can be generated for possible use as a cosmeceutical and functional food material. In this study, we sought to examine the anti-atopic effects of 7,3',4'-trihydroxyisoflavone, an analog of daidzein. Topical application of 7,3',4'-trihydroxyisoflavone reduced Dermatophagoides farina extract-induced atopic dermatitis symptoms in NC/Nga mice. Histological analysis demonstrated that 7,3',4'-trihydroxyisoflavone suppressed D. farina extract-induced infiltration of eosinophils and mast cells into skin lesions. We also found that 7,3',4'-trihydroxyisoflavone significantly reduces the D. farina extract-induced increases in serum IgE and macrophage-derived chemokine (CCL22) levels. We observed that 7,3',4'-trihydroxyisoflavone suppresses atopic markers including macrophage-derived chemokine (CCL22) and thymus and activation-regulated chemokine (CCL17) in HaCaT cells. 7,3',4'-Trihydroxyisoflavone also reduced TNF-α/IFN-γ-induced phosphorylation of ERK1/2 and JNK1/2. These results highlight several desirable properties of 7,3',4'-trihydroxyisoflavone, which support its use as a cosmeceutical ingredient for the treatment of atopic dermatitis.

Synthesis of chitosan derivatives with organoselenium and organosulfur compounds: Characterization, antimicrobial properties and application as biomaterials

In this study, Schiff bases of chitosan (CS) were synthesized using citronellal, citral, and their derivatives containing selenium and sulfur. Organoselenium and organosulfur compounds show attractive biological and pharmaceutical activities, which can be beneficial to CS-based materials. From the characterization analyses, it was found that the CS-derivatives containing organoselenium and organosulfur compounds exhibited the highest conversion degrees (23 and 28%). Biological assays were conducted using films prepared by the blending of CS-derivatives and poly(vinyl alcohol). The antimicrobial evaluation indicated that the film prepared with the sulfur-containing CS was the most active against the tested pathogens (Escherichia coli, Staphylococcus aureus, and Candida albicans) since it reduced considerably their counts (42.5%, 17.4%, and 18.7%). Finally, in vivo assays revealed that this film attenuates atopic dermatitis-like symptoms in mice by suppressing the increase of myeloperoxidase (MPO) activity and reactive species (RS) levels induced by 2,4-dinitrochlorobenzene (DNCB). In summary, CS-derivatives containing chalcogens, mainly organosulfur, are potential candidates for biomedical applications such as for the treatment of chronic skin diseases.