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Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis.

ABSTRACT: Topical agents that are currently available for the treatment of atopic dermatitis may represent a valid approach in the management of mild or mild-moderate cases, whereas they are often supplemented with systemic therapies for handling more complex or unresponsive cases. The most used compounds include topical corticosteroids and calcineurin inhibitors, although their use might be burdened by side effects, poor response, and low patient compliance. Consequently, new innovative drugs with higher efficacy and safety both in the short and long term need to be integrated into clinical practice. A deeper understanding of the complex pathogenesis of the disease has led to identifying new therapeutic targets and to the development of innovative therapeutics. This narrative review aims to collect data on selected promising topical drugs that are in an advanced stage of development.

SUBMITTER: Pinto LM

PROVIDER: S-EPMC9788207 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis.

Pinto Lorenzo Maria LM Chiricozzi Andrea A Calabrese Laura L Mannino Maria M Peris Ketty K

Pharmaceutics 20221210 12

Topical agents that are currently available for the treatment of atopic dermatitis may represent a valid approach in the management of mild or mild-moderate cases, whereas they are often supplemented with systemic therapies for handling more complex or unresponsive cases. The most used compounds include topical corticosteroids and calcineurin inhibitors, although their use might be burdened by side effects, poor response, and low patient compliance. Consequently, new innovative drugs with higher ...[more]

PMID: 36559261

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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:To examine the molecular targets and therapeutic mechanism of a clinically proven Chinese medicinal pentaherbs formula (PHF) in atopic dermatitis (AD), we analyzed the active compounds and core targets, performed network and molecular docking analysis, and investigated interacting pathways. Information on compounds in PHF was obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and target prediction was performed using the Drugbank database. AD-related genes were gathered using the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Network analysis was performed by Cytoscape software and protein-protein interaction was analyzed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources were applied for the enrichment analysis of the potential biological process and pathways associated with the intersection targets between PHF and AD. Autodock software was used to perform protein compound docking analysis. We identified 43 active compounds in PHF associated with 117 targets, and 57 active compounds associated with 107 targets that form the main pathways linked to oral and topical treatment of AD, respectively. Among them, quercetin, luteolin, and kaempferol are key chemicals targeting the core genes involved in the oral use of PHF against AD, while apigenin, ursolic acid, and rosmarinic acid could be used in topical treatment of PHF against AD. The compound-target-disease network constructed in the current study reveals close interactions between multiple components and multiple targets. Enrichment analysis further supports the biological processes and signaling pathways identified, indicating the involvement of IL-17 and tumor necrosis factor signaling pathways in the action of PHF on AD. Our data demonstrated the main compounds and potential pharmacological mechanisms of oral and topical application of PHF in AD.

Dataset Information

Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis.

Publications

Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis.

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