Atopic Dermatitis-like Skin Lesions Research Articles

Improvement of atopic dermatitis with topical application of Spirodela polyrhiza

Ethnopharmacological relevanceSpirodela polyrhiza has been used as a traditional remedy for the treatment of urticarial, acute nephritis, inflammation, as well as skin disease. Aim of studyAtopic dermatitis (AD) is characterized hyperplasia of skin lesion and increase of serum immunoglobulin E (IgE) level. In this study, the topical effects of S. polyrhiza (SP) on 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice model were investigated by several experiments. Materials and methodsBALB/c mice were randomly divided into five groups as NOR, CON, DEX, SP 1, and SP 100 groups (n=5, respectively). To induce atopic dermatitis-like skin lesions, DNCB had been applied on shaved dorsal skin. SP was topically treated to DNCB-induced mice as 1 and 100mg/mL concentrations. Histological changes were showed by hematoxylin and eosin (H&E) staining and the infiltration of mast cells was detected by toluidine blue staining. In addition, the level of IgE and each cytokines were measured and expressions of inflammatory signaling factors were analyzed by western blotting assay. ResultsSP treatment improved a hyperplasia of epidermis and dermis in DNCB-induced AD-like skin lesion. The infiltration of mast cells was also decreased by treatment of SP. In addition, SP reduced the level of IgE in serum and attenuated the secretion of cytokines such as interleukin (IL)-4, IL-6, and tumor necrosis factor (TNF)-α. Treatment of SP also inhibited the expressions of pro-inflammatory mediators including nuclear factor-κB (NF-κB), phosphor-IκB-α, and mitogen-activated protein kinase (MAPK)s. ConclusionsFrom these data, we propose that SP ameliorates AD via modulation of pro-inflammatory mediators. SP may have the potential to be used as an alternative for treatment of AD.

Inhibitory Effect of Valencene on the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice.

Valencene (VAL) isolated from Cyperus rotundus possesses various biological effects such as antiallergic and antimelanogenesis activity. We investigated the effect of VAL on atopic dermatitis (AD) skin lesions and their molecular mechanisms. We topically applied VAL to 1-chloro-2,4-dinitrobenzene (DNCB) sensitized NC/Nga mice. Modified scoring atopic dermatitis index, scratching behavior, and histological/immunohistochemical staining were used to monitor disease severity. RT-PCR, western blotting, and enzyme-linked immunosorbent assay were used to determine the level of IgE, proinflammatory cytokines/chemokines production, and skin barrier proteins expression. Topical application of VAL significantly reduced AD-like symptoms and recovered decreased expression of filaggrin in DNCB-sensitized NC/Nga mice. The levels of serum IgE, IL-1β, IL-6, and IL-13 in skin/splenic tissue were reduced. In vitro studies using TNF-α and IFN-γ treated HaCaT cells revealed that VAL inhibited the exaggerated expression of Th2 chemokines including TARC/CCL17, MDC/CCL22, and proinflammatory chemokines such as CXCL8, GM-CSF, and I-CAM through blockade of the NF-κB pathway. In addition, expression of the skin barrier protein, involucrin, was also increased by VAL treatment. VAL inhibited the production and expression of proinflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW 264.7 cells. These results suggest that VAL may serve as a potential therapeutic option for AD.

Thymic stromal lymphopoietin-induced interleukin-17A is involved in the development of IgE-mediated atopic dermatitis-like skin lesions in mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with elevated levels of allergen-specific IgE. Although thymic stromal lymphopoietin (TSLP) and interleukin-17A (IL-17A) have been considered as important factors in allergic diseases, their relationships in AD have not been fully defined. Here, we show the contribution of TSLP-induced IL-17A responses to IgE-mediated AD-like skin lesions. BALB/c mice passively sensitized by intraperitoneal injections of ovalbumin (OVA)-specific IgE monoclonal antibody (mAb) were challenged with OVA applied to the skin six times. Treatment with anti-TSLP mAb during the second to sixth challenges inhibited IgE-mediated AD-like skin lesions and IL-17A production in lymph nodes. Furthermore, the increased number of IL-17A-producing CD4(+) and γδ T cells in lymph nodes and neutrophilic inflammation in the skin were reduced by anti-TSLP mAb. These findings prompted us to examine the roles of IL-17A. Treatment with anti-IL-17A mAb suppressed the AD-like skin lesions and neutrophilic inflammation; anti-Gr-1 mAb also inhibited them. Furthermore, treatment with CXCR2 antagonist reduced the AD-like skin lesions and neutrophilic inflammation accompanied by the reduction of IL-17A production; the increased CXCR2 expression in the epidermal cells was suppressed by anti-TSLP mAb. Meanwhile, these treatments, except for anti-Gr-1 mAb, inhibited the increased mast cell accumulation in the skin. Collectively, the mechanism of IgE mediating IL-17A-producing CD4(+) and γδ T cells through TSLP by repeated antigen challenges is involved in AD-like skin lesions associated with skin inflammation, such as neutrophil and mast cell accumulation; TSLP may regulate CXCR2 signalling-induced IL-17A production.

Skin manifestations and treatment of graft-versus-host disease

Graft-versus-host disease (GVHD) is an autoimmune disease caused by graft-versus-host reaction, occurring most frequently in patients receiving allogeneic hematopoietic stem cell transplantation and occasionally in patients receiving organ transplantation. It often involves multiple organ systems, of which, skin and mucous membranes are the most frequently affected system with various clinical manifestations. Acute GVHD often appears as measles- or scarlet fever-like skin rashes with severe systemic symptoms such as fever and poor appetite, and may rapidly progress into toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS) in a few days. Lichen planus and sclerodermoid lesions are the most common clinical manifestations of chronic GVHD. With further understanding of this disease in recent years, some new manifestations have been observed, such as psoriasis- and atopic dermatitis-like skin lesions, as well as nail changes in some cases. It is especially important to select appropriate treatment protocols according to clinical manifestations. Glucocorticoids combined with immunosuppressive agents are a conventional treatment for GVHD, and innovative treatments have emerged with the development of therapeutics. Key words: Graft vs host disease; Skin manifestations; Clinical protocols; Biological agents; Mesenchymal stem cell transplantation

Inhibitory Effect of Sargassum fulvellum Water Extract on 2,4-Dinitrochlorobenzene-induced Atopic Dermatitis-like Skin Lesions in Mice

Inhibitory Effect of Sargassum fulvellum Water Extract on 2,4-Dinitrochlorobenzene-induced Atopic Dermatitis-like Skin Lesions in Mice

1β-Hydroxyalantolactone, a sesquiterpene lactone from Inula japonica, attenuates atopic dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in the mouse

Context: 1β-Hydroxyalantolactone (IJ-5) is a sesquiterpene lactone compound isolated from Inula japonica Thunb (Asteraceae). Sesquiterpene lactones have been shown to modulate many processes that influence inflammatory reactions.Objective: The present study examines the protective effect of IJ-5 on atopic dermatitis (AD) in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB).Materials and methods: AD-like skin lesions were induced in Balb/c mice by sensitizing once with painting 100 μL of 5% DNCB on their shaved back skin and then challenging with 20 μL of 0.2% DNCB five times on their right ears at 3 d interval starting on day 5 post-sensitization. IJ-5 was administrated intraperitoneally at 10 mg/kg 1 h before each DNCB challenge.Results: IJ-5 treatment attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, IL-4, and IL-6 in IJ-5-treated mice were reduced by 54.7, 56.5, and 53.0%, respectively, while the mRNA levels of TNFα, IL-1, IL-4, and IL-6 in back skin lesions of IJ-5-treated mice were reduced by 47.7, 61.5, 57.5, and 58.5%, respectively, compared with untreated controls. Histopathological examination showed that IJ-5 treatment decreased DNCB-induced hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in both ear and back skins. Moreover, IJ-5 suppressed the expression of TNFα, IL-1, and IL-6 with IC50 values of 6.58, 9.48, and 7.01 μM, respectively, and inhibited the activation of NF-κB pathway in TNFα-stimulated HaCat cells.Discussion and conclusion: The present study demonstrates the protective effects of IJ-5 against AD-like skin inflammation and highlights IJ-5 as a potential therapeutic agent for AD.

Effects of topically applied rapamycin and mycophenolic acid on TNCB-induced atopic dermatitis-like skin lesions in NC/Nga mice

Rapamycin (RPM) and mycophenolic acid (MPA) are immunosuppressive drugs approved for use in preventing transplant rejection. These drugs have also been used in the field of dermatology as glucocorticoid sparing agents for autoimmune and inflammatory disorders such as atopic dermatitis (AD). The aim of this study was to investigate the therapeutic effect of topically applied RPM and/or MPA on AD-like skin lesions in NC/Nga mice. RPM (0.04% - 4%), MPA (0.2% - 5%), and formulations of both agents at various ratios were administrated topically to NC/Nga mice with 2-chloro-1,3,5-trinitrobenzene (TNCB)-induced AD-like skin lesions. The therapeutic effects of topical RPM, MPA, and the mixed formulations in TNCB-treated NC/Nga mice were assessed by measuring skin severity scores, ear thickness, and histological changes in the lesioned skin including mast cell count and total serum IgE levels. Expression of interleukin (IL)-4, and interferon (IFN)-γ was also assessed. Topical 4% RPM and/or 1% MPA treatment significantly improved clinical signs of AD such as erythema, edema, excoriation, and dryness on day 29 (P<0.05). In addition, 4% RPM, 1% MPA, and the mixed formulations significantly decreased epidermal thickening, dermal edema, and cellular infiltration into the dermis compared with the vehicle. RPM (4%) and/or MPA (1%) significantly reduced the expression of IL-4 and IFN-γ mRNA and protein levels compared with the vehicle (P<0.05). No significant change in the levels of total serum IgE was induced by topical 4% RPM and/or 1% MPA. The present results demonstrated that topical 4% RPM and/or 1% MPA improved TNCB-induced AD-like lesions of NC/Nga mice by suppressing expression of Th2-related cytokines (IL-4) and Th1-related cytokines (IFN-γ). These findings suggest that RPM and/or MPA may be promising topical therapeutic candidates for the treatment of AD.

Improvement of atopic dermatitis-like skin lesions by IL-4 inhibition of P14 protein isolated from Lactobacillus casei in NC/Nga mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, with a complex etiology encompassing immunologic responses. AD is frequently associated with elevated serum immunoglobulin (Ig) E levels and is exacerbated by a variety of environmental factors, which contribute to its pathogenesis. However, the etiology of AD remains unknown. Recently, reports have documented the role of lactic acid bacteria (LAB) in the treatment and prevention of AD in humans and mice. The LAB, Lactobacillus casei (LC), is frequently used in the treatment of AD. To identify the active component of LC, we screened fractions obtained from the ion exchange chromatography of LC extracts. Using this approach, we identified the candidate protein, P14. We examined whether the P14 protein has anti-atopic properties, using both in vitro and in vivo models. Our results showed that the P14 protein selectively downregulated serum IgE and interleukin-4 cytokine levels, as well as the AD index and scratching score in AD-like NC/Nga mice. In addition, histological examination was also effective in mice. These results suggest that the P14 protein has potential therapeutic effects and that it may also serve as an effective immunomodulatory agent for treating patients with AD.

Bathing Effects of Various Seawaters on Allergic (Atopic) Dermatitis-Like Skin Lesions Induced by 2,4-Dinitrochlorobenzene in Hairless Mice.

We evaluated the preventive effects of four types of seawater collected in Republic of Korea on hairless mice with 2,4-dinitrochlorobenzene- (DNCB-) induced allergic/atopic dermatitis (AD). The anti-inflammatory effects were evaluated by measuring tumor necrosis factor- (TNF-) α and interleukins (ILs). Glutathione (GSH), malondialdehyde (MDA), superoxide anion, and inducible nitric oxide synthase (iNOS) were measured to evaluate the antioxidant effects. Caspase-3 and poly (ADP-ribose) polymerase (PARP) were observed to measure the antiapoptotic effects; matrix metalloproteinase- (MMP-) 9 levels were also evaluated. Mice with AD had markedly higher clinical skin severity scores and scratching behaviors; higher TNF-α and ILs (1β, 10, 4, 5, and 13) levels; higher MDA, superoxide anion, caspase-3, PARP, and MMP-9 levels; and greater iNOS activity. However, the severity of AD was significantly decreased by bathing in seawaters, but it did not influence the dermal collagen depositions and skin tissue antioxidant defense systems. These results suggest that bathing in all four seawaters has protective effects against DNCB-induced AD through their favorable systemic and local immunomodulatory effects, active cytoprotective antiapoptotic effects, inhibitory effects of MMP activity and anti-inflammatory and antioxidative effects.

Drug-loaded PLGA-mPEG microparticles as treatment for atopic dermatitis-like skin lesions in BALB/c mice model

This study evaluated the feasibility of mizolastine-loaded microparticles as therapy for atopic dermatitis. Microparticles have been researched for decades as a controlled-release drug delivery system, but seldom been used as treatment for skin disease. In this research, we induced dermatitis in BALB/c mice model by repeated topical application of dinitrofluorobenzene and compared the mizolastine microparticles injection and daily mizolastine injection treatment. The results showed that the mizolastine microparticles treatments significantly inhibited ear thickness and dermatitis index in dermatitis model compared with the dermatitis mice without treatment, showing a similar curative effect compared with daily mizolastine injection treatment, and the improvement continued for several days. Inflammatory cells infiltration into the ears and the plasma level of immunoglobulin E were also suppressed by mizolastine microparticles according to the histopathology analysis. In conclusion, the results suggested that drug-loaded microparticles could be a proper candidate for the treatment of skin diseases.

In vivo assessment of the effect of taxifolin glycoside on atopic dermatitis-like skin lesions using biomedical tools in NC/Nga mice.

Noninvasive methods of assessment are widely used in clinical trials. However, such methods have not been established in atopic dermatitis (AD), which is a chronic inflammatory skin disease. To demonstrate, using biomedical tools, the benefits of a new substance, taxifolin glycoside (TAX), in an AD model, the NC/Nga mouse. We evaluated the efficacy of topical TAX for AD by measuring clinical skin severity score, cytokine expression and serum IgE level, and by using biomedical measures (vapometry and corneometry). Topical TAX was applied to AD-induced NC/Nga mice for 3 weeks. The anti-inflammatory effects of this compound were demonstrated noninvasively using biomedical tools and immunological assays. Our method of AD assessment using biomedical tools is more objective and accurate than visual inspection. The results obtained using the biomedical tools were identical to those obtained using immunological assays. In vivo biomedical tools are useful for diagnosing and monitoring treatment effects in AD.

백선피(白鮮皮) 추출물이 DNCB로 유발된 NC/Nga 생쥐의 아토피 피부염에 미치는 영향

Objectives Dictamni Radicis Cortex extracts (DRC) has been known to suppress allergic reaction, however the cellular target of DRC and its mode of action remain unclear. The purpose of this study is to investigate the effects of Dictamni Radicis Cortex extracts on DNCB induced atopic dermatitis-like skin lesions of NC/Nga mouse. Methods This study was designed to investigate the effects of DRC extract in the DNP-IgE-induced activation of MC/9 murine mast cell lines in vitro and in the DNCB-induced activation of NC/Nga mouse in vivo. For this investigation, We examined IL-4, IL-5, IL-6, IL-13, TNF-<TEX>${\alpha}$</TEX> and GM-CSF mRNA expression by Real-time PCR, IL-13, MIP-<TEX>$1{\alpha}$</TEX> production by ELISA analysis and manifestations of NFAT1, NFAT2, AP-1 and NF-<TEX>${\kappa}B$</TEX> p65 transcription factors by western blotting in vitro. Then, we examined WBC, eosinophil and neutrophil in NC/Nga mouse, IL-5, IL-13 in serum, IFN-<TEX>${\gamma}$</TEX>, IL-4 in the spleenocyte culture supernatant, the absolute cell numbers of <TEX>$CD4^+$</TEX>, <TEX>$CD8^+$</TEX>, <TEX>$^+Gr-1^+CD11b$</TEX>, <TEX>$B220^+CD23^+$</TEX> in the ALN, PBMCs and dorsal skin, IL-5, IL-13 in the dorsal skin by Real-time PCR and the distribution of mast cells by H&E and toluidine blue. Results In vitro the mRNA expression of IL-4, IL-5, IL-6, IL-13, TNF-<TEX>${\alpha}$</TEX>, GM-CSF and IL-13, MIP-<TEX>$1{\alpha}$</TEX> production by ELISA analysis were completely abolished by DRC and the western blot analysis decreased the expression of mast cell-specific transcription factors including NFAT-1, NF-<TEX>${\kappa}B$</TEX> p65. In vivo DRC oral adminstration also decreased the counts of WBC, eosinophils and inflammatory cytokines such as IL-13 and IgE in the serum. DRC oral adminstration elevated IL-4 level in the spleenocyte culture supernatant. DRC oral adminstration decreased total ALN cells, total skin cells, cell numbers of <TEX>$CD4^+$</TEX>, <TEX>$B220^+CD23^+$</TEX> in the ALN, <TEX>$^+Gr-1^+CD11b$</TEX> in the PBMCs and <TEX>$CD4^+$</TEX>, <TEX>$CD8^+$</TEX> in the dorsal skin. The mRNA expression of IL-5, IL-13, thickness of epidermis, inflammation immune cells and mast cells were abolished by DRC in the dorsal skin. Conclusions Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mouse were much improved by DRC oral adminstration. These results, therefore, suggest that DRC can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis induced in NC/Nga mouse, and may play an important role in recovering AD symptoms.

Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles.

BackgroundAtopic dermatitis is a chronic, noncontiguous, and exudative disorder accompanied by perivascular infiltration of immune mediators, including T-helper (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The current study explores the immunomodulatory and histological effects of nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC).MethodsIn this study, HC, the least potent topical glucocorticoid, was administered transcutaneously as chitosan NPs. The pharmacological and immunological effects of the NP-based HC delivery on the alleviation of 2,4-dinitrofluorobenzene-induced atopic dermatitis (AD)-like skin lesions were evaluated using the NC/Nga mouse model.ResultsIn vivo Dino-Lite® microscopic assessment revealed that the NP-based formulation displayed a remarkable ability to reduce the severity of the pathological features of AD (dermatitis index, 3.0). The AD suppressive activity of the NP-based topical formulation was expected owing to the interruption of a series of immunopathological events, including the production of immunoglobulin E, release of histamine, and expression of prostaglandin-E2 and vascular endothelial growth factor-α in the sera and skin of the tested animals. Analysis of the cytokine expression in AD-like skin lesions further revealed that the NP-based formulation inhibited the pathological expression of interleukin (IL)-4, IL-5, IL-6, IL-13, IL-12p70, interferon-γ, and tumor necrosis factor-α in serum and skin homogenates of NC/Nga mice. Further, our histological findings indicated that the NP-based formulation inhibited fibroblast infiltration and fragmentation of elastic fibers, further supporting the clinical importance of these formulations in maintaining the integrity of elastic connective tissues.ConclusionThe current investigation suggests that NP-mediated transcutaneous delivery of HC could be considered an effective therapeutic approach to manage dermatitis.

Anti-allergic mechanisms of Japanese herbal medicine, yokukansan on mast cells.

We previously reported that the addition of orally administered yokukansan (YKS), a traditional Japanese herbal medicine, to the standard regimen using histamine H1-receptor inhibitors was effective in controlling refractory chronic urticaria, but the mechanism remained unknown. YKS has also been reported to be effective on inhibiting the development of atopic dermatitis-like skin lesions in NC/Nga mice. As known, the release of various chemical mediators including histamine from degranulated mast cells is strongly related to the mechanism of these diseases. Thus the purpose of this study was to examine the mechanisms behind the medicinal effects of YKS on mast cells using an in vitro system and rat basophil leukemia (RBL-2H3) cells. The degree of degranulation was measured by β-hexosaminidase secretion assay and intracellular calcium influx assay. ELISA for cytokines (TNF-α and IL-4) was also conducted using cell culture media. Furthermore, we investigated the effects of YKS on the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokine production (IL-8) in human dermal microvascular endothelial cells using gene-transcriptional- and immunohisotoligical analysis. We found that YKS inhibited secretion of β-hexosaminidase, intracellular calcium increase, production of TNF-α and ICAM-1 expression, and that several YKS ingredients may be the key effectors. In conclusion, YKS may suppress several mast cell functions such as degranulation and calcium increase that eventually inhibits the release of proinflammatory cytokines. Furthermore, YKS suppresses ICAM-1 expression on human microvascular endothelial cells. These findings may promote our understanding of the beneficial effects of YKS on mast cell-associated allergic diseases.

A New Furfural Diglycoside and Other Carbohydrate Derivatives from Fermented Beverage of Prunus mume Fruit

Prunus mume Sieb. et Zucc. (Rosaceae) is a deciduous fruit tree that is distributed widely in East Asian. Its fruit, commonly known as Maesil in Korea, is a traditional raw ingredient used in herbal medicines and healthy foods in Korea, China, and Japan. In particular, a beverage produced by the fermentation of a mixture of green P. mume fruit and sugar is popular in Korea. Recent studies have shown that this fermented beverage, which contains a variety of probiotics, enhances immune activity and suppresses the development of atopic dermatitis-like skin lesions and 7,12-dimethylbenz[α]anthracene (DMBA)and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin carcinogenesis in mice. Despite these findings, the chemical constituents of fermented P. mume beverage have yet to be characterized. In the present study, 19 compounds, including a new furfural diglycoside, 5-[β-D-fructopyranosyl-(2→6)-α-D-glucopyranosyloxymethyl]-2-furancarboxaldehyde (1), 16 carbohydrate derivatives (2-10 and 12-18), and two additional compounds (11 and 19) were isolated from samples of fermented P. mume fruit beverage. This is the first report detailing the chemical composition of fermented P. mume beverage and provides a useful reference for further biological investigation. This report describes the isolation and structural elucidation of compounds 1-19. The known compounds that were isolated from the fermented beverage of P. mume fruit were identified by comparisons of their physical and spectroscopic data with those reported in the literature. They were identified as 5hydroxymethyl-2-furfural (2), α-methoxy-2,5-furandimethanol (3), benzyl-β-D-glucopyranoside (4), benzyl-β-Dglucopyranosyl-(1→6)-β-D-glucopyranoside (5), benzyl-βD-xylopyranosyl-(1→6)-β-D-glucopyranoside (6), benzylα-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside (7), benzyl-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (8), (2E)-7-hydroxy-3,7-dimethyl-2-octenyl α-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside (9), (2E)-7-hydroxy-3,7-dimethyl-2-octenyl α-L-arabinofuranosyl-(1→6)-βD-glucopyranoside (10), methyl (E)-p-coumarate (11), 3O-p-coumaroylsucrose (12), 3-O-feruloylsucrose (13), nbutyl-β-D-glucopyranoside (14), sucrose (15), methyl βD-fructopyranoside (16), D-glucopyranose (an equilibrium mixture of 64% β-D-glucopyranose and 36% α-D-glucopyranose in solution, 17), D-fructose (an equilibrium mixture of 70% β-D-fructopyranose and 22% β-D-fructofuranose in solution, 18), and tyrosol (19) (Figure 1). Compound 1 was obtained as a colorless syrup with a positive optical rotation of +47.2 (c = 1.0, MeOH). Its molecular formula was determined to be C18H26O13 by highresolution electrospray ionization mass spectrometry (HRESI-MS) at m/z 473.1295 [M+Na] (calcd for C18H26O13Na, α [ ]D 18

Morus alba L. suppresses the development of atopic dermatitis induced by the house dust mite in NC/Nga mice.

BackgroundMorus alba, a medicinal plant in Asia, has been used traditionally to treat diabetes mellitus and hypoglycemia. However, the effects of M. alba extract (MAE) on atopic dermatitis have not been verified scientifically. We investigated the effects of MAE on atopic dermatitis through in vitro and in vivo experiments.MethodsWe evaluated the effects of MAE on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7, as well as thymus and activation-regulated chemokine (TARC/CCL17) in HaCaT cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for four weeks, and the protective effects of MAE were investigated by measuring the severity of the skin reaction on the back and ears, the plasma levels of immunoglobulin E (IgE) and histamine, and histopathological changes in the skin on the back and ears.ResultsMAE suppressed the production of NO and PGE2 in RAW 264.7 cells, as well as TARC in HaCaT cells, in a dose-dependent manner. MAE treatment of NC/Nga mice reduced the severity of dermatitis and the plasma levels of IgE and histamine. MAE also reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration in the skin on the back and ears.ConclusionOur results suggest that MAE has potent inhibitory effects on atopic dermatitis-like lesion and may be a beneficial natural resource for the treatment of atopic dermatitis.

Topical application of Kochia scoparia inhibits the development of contact dermatitis in mice

Ethnopharmacological relevanceKochia scoparia (Chenopodiaceae) has been reported to have anti-nociceptive, anti-inflammatory, anti-allergic, and anti-pruritic actions. This study investigated the anti-inflammatory effects of externally applied Kochia scoparia water extract (KSW) in 2,4-dinitrochlorobenzene (DNCB)-induced contact dermatitis mouse model. Materials and methodsTo develop atopic dermatitis-like skin lesions, 100μL of 1% DNCB in acetone/olive oil (4:1) had been applied for three days on shaved dorsal skin. 1% KSW was topically applied to DNCB-induced mice. After KSW treatment, histological analysis was measured by hematoxylin eosin staining. The cytokine and pro-inflammatory expressions were examined using reverse transcription polymerase chain reaction and western blotting analysis. ResultsHistological studies showed that hyperplasia of the epidermis and dermis in the KSW treated group was markedly decreased as compared with the DNCB group. The expression levels of pro-inflammatory cytokine such as IL-1β, and TNF-α mRNA were significantly reduced by topical application of KSW, whereas these cytokines were increased in DNCB-induced dorsal skin. In addition, NF-κB expression was inhibited by KSW treatment in DNCB-induced mice. Similarly, KSW treatment significantly suppressed the expression of several MAP kinases, including ERK1/2, p38, and JNK compared to their expression in DNCB-induced mice. ConclusionsThese findings indicated that KSW ameliorates contact dermatitis via inhibition of the production of several inflammatory mediators. Therefore, external application of KSW may be used for the treatment of contact dermatitis as an alternative therapy.

Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin–basophil axis

Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy. We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy. Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic dermatitis-like skin lesion, followed by intragastric antigen challenge. Antigen-specific serum IgE levels and T(H)2 cytokine responses were measured by ELISA. Expression of type 2 cytokines and mast cell proteases in the intestine were measured by using real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by using flow cytometry. In vivo basophil depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For cell-transfer studies, the basophil population was expanded in vivo by means of hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA plasmid. Sensitization to food allergens through an atopic dermatitis-like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific T(H)2 cytokine responses, increased antigen-specific serum IgE levels, and accumulation of mast cells in the intestine, promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy, whereas transfer of TSLP-elicited basophils into intact skin promoted disease. Epicutaneous sensitization on a disrupted skin barrier is associated with accumulation of TSLP-elicited basophils, which are necessary and sufficient to promote antigen-induced intestinal food allergy.

The β-sitosterol attenuates atopic dermatitis-like skin lesions through down-regulation of TSLP

The compound β-sitosterol (BS) is one of the most common forms of phytosterols and has anti-cancer, anti-oxidant, anti-bacterial, and anti-inflammatory effects. However, the effect of BS on atopic dermatitis (AD) has not been elucidated. Therefore, we investigated whether BS would be an effective treatment against AD. We treated BS on 2,4-dinitrofluorobenzene (DNFB)-induced AD-like skin lesions in NC/Nga mice, anti-CD3/anti-CD28-stimulated splenocytes, and phorbol myristate acetate/calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. Histological analysis, ELISA, PCR, caspase-1 assay, and Western blot analysis were performed. BS reduced the total clinical severity in DNFB-treated NC/Nga mice. Infiltration of inflammatory cells and number of scratching were clearly reduced in the BS-treated group compared with the DNFB-treated group. BS significantly reduced the levels of inflammation-related mRNA and protein in the AD skin lesions. BS significantly reduced the levels of histamine, IgE, and interleukin-4 in the serum of DNFB-treated NC/Nga mice. The activation of mast cell-derived caspase-1 was decreased by treatment with BS in the AD skin lesions. BS also significantly decreased the production of tumor necrosis factor-α from the stimulated splenocytes. In the stimulated human mast cell line, HMC-1 cells, increased intracellular calcium levels were decreased by treatment with BS. Further, BS inhibited the production and mRNA expression of TSLP through blocking of caspase-1 and nuclear factor-κB signal pathways in the stimulated HMC-1 cells. These results provide additional evidence that BS may be considered an effective therapeutic drug for the treatment of AD.

青大豆抽出物の機能性について

Hot water extracts of green soybean, Glycine max (WEGS) significantly decreased the levels of ovalbumin (OVA)-specific IgE in mice and significantly suppressed toluene diisocyanate-induced nasal mucosa secretion. An open-label human pilot study including 16 subjects with Japanese cedar pollinosis (JCP) was conducted. The symptom scores for JCP were better in the long-term WEGS intake group than in the short-term intake group. WEGS have great potential as an orally active immune modulator for the treatment of various allergic diseases. We conducted a preliminary investigation of the effects of visible light irradiation on plant extracts, and observed a strong suppressive effect on interleukin (IL)-2 expression in Jurkat cells following treatment with visible light-irradiated ethanol extract from green soybeans (LIEGS). This effect was produced only by extracts from green soybeans and not soybeans of other colors. LIEGS suppressed lipopolysaccharide-induced IL-6, IL-12, and TNF-α expression levels in human monocyte THP-1 cells in a concentration-dependent manner. LIEGS suppressed the development of atopic dermatitis-like skin lesions and reduced the dermatitis scores of NC/Nga mice.