Dataset Information

Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum.

ABSTRACT:

Background

Gami-Cheongyeul-Sodok-Eum (GCSE), an herbal formula of traditional Korean medicine, comprises nine herb components. GCSE has various biological activities such as anti-inflammatory, anti-bacterial and anti-viral activities. However, it is still unclear whether GCSE has any immunomodulatory effect on atopic dermatitis (AD).

Methods

GCSE was treated to primary B cells and CD4+ T cells isolated from atopic mice to compare its inhibitory effects on IgE secretion and cytokine expression. Experimental AD was established by alternative treatment of 2, 4-dinitrochlorobenzene (DNCB) and house dust mite extract to the ears of BALB/c mice. GCSE was topically applied to ears of atopic mice every day for 3 weeks. AD progression was analyzed by measuring ear thickness, serum IgE level, histological examination of ear tissue by H&E staining and cytokine profile of CD4+ T cells and CD19+ B cells by real time PCR and ELISA.

Results

Treatment of GCSE significantly reduced IgE production and expression of AD associated pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13, IL-17, TNF-?, and IFN-? by lymphocytes isolated from AD-induced mice. Topical application of GCSE on the ears of AD-induced mice significantly reduced ear thickness, clinical score and lymphocytes infiltration to ears as compared to control group. GCSE treatment also reduced serum IgE level and the levels of major pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13 and IL-17. In addition, GCSE treatment significantly increased Foxp3 expression level.

Conclusions

The protective effect of GCSE in experimental AD is mediated by inhibition of IgE production, by reduction in the levels of pathogenic cytokines and by induction of Foxp3, all of which are suggesting the beneficial effect of GCSE on modulating atopic dermatitis.

SUBMITTER: Hwang JS

PROVIDER: S-EPMC3832229 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum.

Hwang Ji Sun JS Kim Jung-Eun JE Yu Young-Beob YB Im Sin-Hyeog SH

BMC complementary and alternative medicine 20131111

<h4>Background</h4>Gami-Cheongyeul-Sodok-Eum (GCSE), an herbal formula of traditional Korean medicine, comprises nine herb components. GCSE has various biological activities such as anti-inflammatory, anti-bacterial and anti-viral activities. However, it is still unclear whether GCSE has any immunomodulatory effect on atopic dermatitis (AD).<h4>Methods</h4>GCSE was treated to primary B cells and CD4+ T cells isolated from atopic mice to compare its inhibitory effects on IgE secretion and cytokin ...[more]

PMID: 24499290

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Project description:BackgroundAtopic dermatitis (AD) is a common pruritic inflammatory skin disease with increasing prevalence. It can manifest with many different clinical phenotypes; however, in its chronic stage, hyperpigmentation, excoriation, lichenification, and dryness are the main symptoms. Jaungo comprises two herbs, Lithospermi radix and Angelica gigantis radix, and three carrier oils, and is an approved herbal ointment for xerosis cutis in Korea. In past studies, we demonstrated that Jaungo had anti-inflammatory and antiallergic activity in in vitro and in vivo AD models; however, there are few relevant randomized controlled clinical trials on Jaungo in AD.Methods/designA randomized, double-blind, placebo-controlled, single-center, phase IIa clinical trial was designed to investigate the safety, preliminary efficacy, and dose response of Jaungo in AD. The study protocol was approved by the Institutional Review Boards of the Kyung Hee University Korean Medicine Hospital (No. KOMCIRB-160617-HR-027) and the Korea Food and Drug Administration (No. 30907). The study aims to enroll 34 AD patients to be randomly distributed among three parallel groups: treatment 1, treatment 2, and the placebo group. Treatment group 1 applies Jaungo twice a day, while treatment group 2 applies Jaungo and the placebo ointment once a day, separately, and the placebo group applies the placebo ointment twice a day, for a total of 3 weeks each. Participants will be evaluated for eczema before and after the application of the ointments based on several parameters including the Eczema Area and Severity Index, the SCORing of Atopic Dermatitis Index, the Dermatology Life Quality Index, transepidermal water loss, total IgE level, eosinophil count, and IL-17, IL-22, and IFN-γ levels.DiscussionThe trial is currently ongoing and the enrollment of subjects has been initiated. There is an urgent need to develop a drug for the treatment of dry, hyperpigmented, scaly, and thickened skin in chronic-stage AD. This study will determine the efficacy and safety of Jaungo in AD, providing evidence for specific AD symptoms treated by Jaungo.Trial registrationClinical Trials.gov, identifier: NCT02900131 . Registered on 2 September 2016. Korea Clinical Research Information Service, identifier: KCT0002060 . Registered on 22 July 2016.

Project description:BACKGROUND:Skin barrier dysfunction plays a key role in atopic dermatitis (AD). This impairment is related to altered composition and metabolism of epidermal sphingolipids and a deficiency of ceramides. Glycosaminoglycans (GAGs), and especially hyaluronic acid, could be useful in the management of AD. This study aimed to evaluate the effects of a novel topical treatment consisting of sphingolipids and GAGs extracts in dogs with AD. This formulation is different from previously tested products because the sphingolipid extract contained high amounts of sphingomyelin, a precursor of ceramides, and this has been shown to enhance endogenous synthesis of ceramides and to increase lamellar-related structures in vitro. Thus, it was hypothesized that this formulation could improve clinical disease and skin barrier function in patients with AD. RESULTS:Twelve house dust mite (HDM) allergic atopic beagle dogs were randomized into two groups: control (n = 6; no treatment) or treatment (n = 6; topical sphingolipids and GAGs twice weekly for 8 weeks). Dogs were challenged with allergen twice weekly and the severity of dermatitis was scored using the canine atopic dermatitis and extent severity index (CADESI-03) once weekly. Skin barrier function (measurement of transepidermal water loss) and severity of pruritus (both pruritus visual analog scale [PVAS] and pruritus timed episodes) were assessed at 0, 4 and 8 weeks of treatment. Assessments were done by personnel unaware of group allocation. Complete blood count, serum biochemistry and stratum corneum (SC) lipidomics analyses were done at baseline and at week 8. Compared to baseline, significant increases in CADESI (P = 0.0003) and PVAS (P = 0.041) were observed only in the control group, and SC polyunsaturated fatty acids increased significantly only with treatment (P = 0.039). Compared to control, treatment group had a significantly lower CADESI after 1 week (P = 0.0078) and a significantly lower PVAS after 8 weeks (P = 0.0448). Treatment was well tolerated. CONCLUSIONS:In this study in dogs with AD, a new topical formulation containing sphingomyelin-rich sphingolipids plus GAGs extracts attenuated the clinical worsening induced by HDM, supporting its use in atopic patients, either as an adjunctive treatment or used as monotherapy in certain cases.

Project description:Importance:Topical medication is the central treatment for patients with atopic dermatitis (AD), but the options are limited. Phosphodiesterase 4 (PDE4) inhibitors are a new candidate for AD therapy. Objective:To evaluate the efficacy and safety of topical PDE4 inhibitors in mild to moderate AD. Data Sources:Clinical trials were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials, Chinese medical databases (Wanfang, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database), ClinicalTrials.gov, and other trial registries from inception to August 15, 2018. No restrictions on languages were placed. Study Selection:Only double-blind randomized clinical trials with topical PDE4 inhibitors vs topical vehicle treatment for patients with mild to moderate AD were included. Data Extraction and Synthesis:Two reviewers independently extracted study features, intervention details, and outcomes. A meta-analysis was performed using the random-effects model. The Cochrane Collaboration's risk of bias assessment tool was used to assess the risk of bias. Funnel plots and Egger tests were used to assess the publication bias. Main Outcomes and Measures:Changes from baseline in target lesion score were expressed in terms of standardized mean differences (SMDs) with 95% CIs. Outcomes of investigators' assessment and safety were expressed in terms of relative risk with 95% CIs. Results:Seven studies were identified, which included 1869 patients with mild to moderate AD. Overall, compared with the topical vehicle control, topical application of PDE4 inhibitors was associated with a significant decrease in target lesion score (SMD -0.40; 95% CI, -0.61 to -0.18; P < .001) and a higher response rate in investigators' assessment of clear or almost clear skin (relative risk, 1.50; 95% CI, 1.33-1.70; P < .001). There was no difference in treatment-related adverse events or in adverse events that required discontinuation of therapy. Subgroup analyses indicated that after 14 and 28 days of therapy with PDE4 inhibitors, target lesion score was significantly decreased. However, these beneficial effects were displayed only for the PDE4 inhibitors crisaborole and AN2898 (crisaborole at day 14: SMD, -0.59; 95% CI, -1.15 to -0.02; P = .04; AN2898 at day 14: SMD, -0.76; 95% CI, -1.38 to -0.13; P = .02; crisaborole at day 28: SMD, -0.86; 95% CI, -1.44 to -0.28; P = .004; AN2898 at day 28: SMD, -0.68; 95% CI, -1.30 to -0.05; P = .03). Heterogeneity was not significant across studies. Conclusions and Relevance:This meta-analysis suggests that topical PDE4 inhibitors are a safe and effective treatment for mild to moderate AD. Current evidence supports the use of crisaborole or AN2898 as the choice of maintenance or sequential therapy for mild to moderate AD.

Project description:There is no established protocol for the development of an experimental canine atopic dermatitis model in laboratory beagles. This study aimed to establish an experimental model that mimics spontaneous canine atopic dermatitis (CAD) clinically, immunologically, and microbiologically, by repeated epicutaneous applications of mite antigens and to describe the entire process including sensitization and provocation in detail for reproducibility. Six intact male laboratory beagle dogs aged 14 months were included in this study. During the sensitization and provocation phase, the house dust mite (HDM) paste consisted of Dermatophagoides farinae (Der f ) and mineral oil, which was applied focally to the 10 × 10 cm area of the right groin as evenly as possible. Further, 120 mg of Der f was applied to each dog twice a week for 12 weeks during the sensitization phase and 25 mg and 120 mg was applied to each dog for the first 2 weeks and subsequent 2 weeks, respectively, during the provocation phase. Thereafter, the applied area was covered with a dressing. Skin lesions including erythema, hyperpigmentation, excoriation, and lichenification were induced and exacerbated gradually through the experimental time course in all six dogs. The canine atopic dermatitis extent and severity index (CADESI) score and transepidermal water loss (TEWL) significantly increased after sensitization and provocation. IL-13 and IL-31 levels increased significantly after provocation as a result of the activation of the T helper-2 (Th2) response. On the contrary, the IL-10 levels decreased significantly after sensitization, which suggested a suppression of Tregs activity. After the completion of provocation, skin microbiome analysis showed that Firmicutes was the most abundant phylum, which indicated bacterial dysbiosis. This study demonstrated that epicutaneous application of HDM in beagle dogs resulted in the elevation of serum HDM-specific IgE levels and clinical atopic scores, a high TEWL, and microbiome dysbiosis resembling spontaneous CAD. These results suggest that this tailored protocol of epicutaneous exposure to Der f may provide support for the development of the experimental CAD model in laboratory beagles.

Dataset Information

Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum.

Background

Methods

Results

Conclusions

Publications

Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum.

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