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基于羟基酪醇的配方对皮肤炎症的安全性和疗效:在重建人体表皮模型上的体外评价。

Safety and efficacy of hydroxytyrosol-based formulation on skin inflammation: in vitro evaluation on reconstructed human epidermis model.

机构信息

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Via Ferdinando Stagno d'Alcontres, 31, Viale SS. Annunziata, 98166, Messina, ME, Italy.

Fondazione Prof. A. Imbesi, University of Messina, Piazza Pugliatti, 1, Messina, ME, Italy.

出版信息

Daru. 2019 Jun;27(1):283-293. doi: 10.1007/s40199-019-00274-3. Epub 2019 May 26.

DOI:10.1007/s40199-019-00274-3
PMID:31129807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6593001/
Abstract

BACKGROUND

Atopic dermatitis is a multifactorial immune-mediated skin disorder characterized by an alteration of epidermal barrier function and onset of skin lesions, which range from mild erythema to severe lichenification. Treatment consists in hydration with possible use of topical or immunomodulatory corticosteroids, which, however sometimes showed side effects. Recently, the interest in natural compounds has grown significantly and among these, hydroxytyrosol (HT) plays a pivotal role due to its strong and well-known anti-inflammatory activity.

OBJECTIVES

The aim of this study was to investigate the safety and efficacy of Fenolia® Eudermal Cream 15 (HT-based formulation) on epidermal barrier impaired as consequence of skin injury.

METHODS

Whit this purpose, morphologic and structural as well as anti-inflammatory evaluations, after treatment with pro-inflammatory mediators (PBS 1 X and LPS) and HT-based formulation on reconstructed human epidermis (RHE) were carried out by qualitative (hematoxylin/eosin- and immunostaining) and quantitative (MTT assay, IL-1α and IL-8 release by ELISA) techniques. Furthermore, HT absorption through the epidermal barrier was evaluated by RP-LC-DAD analysis.

RESULTS

A rise in the thickness of the epidermis as well as an appropriate maturation and protein expression (Loricrin, Fillagrin, E-Cadherin and Cytokeratins 5&6) were detected in treated RHE samples. In particular, the HT-based formulation was found to stimulate cell proliferation, as evidenced by the significant increase in Ki67 expression, which suggests the involvement of repair mechanisms, increasing epithelial regeneration and differentiation and improving the epidermal barrier effect. Furthermore, HT-based formulation showed a statistically significant anti-inflammatory activity by reducing both IL-1α and IL-8 release by RHE tissues, greater than the reference drug dexamethasone. Finally, excellent transcutaneous absorption values were found for HT, demonstrating how this new formulation increases the availability of the bioactive compound.

CONCLUSIONS

In light of these results, Fenolia® Eudermal Cream 15 could be an effective agent to counteract atopic dermatitis. Graphical abstract Safety and efficacy of hydroxytyrosol-based formulation on skin inflammation: in vitro evaluation on reconstructed human epidermis model.

摘要

背景

特应性皮炎是一种多因素免疫介导的皮肤疾病,其特征为表皮屏障功能改变和皮肤损伤,从轻度红斑到严重的苔藓样变。治疗包括保湿,可能使用局部或免疫调节皮质类固醇,但有时会出现副作用。最近,人们对天然化合物的兴趣显著增加,其中羟基酪醇 (HT) 因其强大而众所周知的抗炎活性而发挥关键作用。

目的

本研究旨在探讨 Fenolia® Eudermal Cream 15(基于 HT 的配方)对因皮肤损伤而受损的表皮屏障的安全性和疗效。

方法

为此,在重建的人表皮 (RHE) 上用促炎介质 (PBS 1X 和 LPS) 和基于 HT 的配方处理后,通过定性 (苏木精/伊红和免疫染色) 和定量 (MTT 测定法、IL-1α 和 IL-8 通过 ELISA 释放)技术进行形态和结构以及抗炎评估。此外,通过 RP-LC-DAD 分析评估 HT 穿过表皮屏障的吸收。

结果

在处理过的 RHE 样本中,发现表皮厚度增加,成熟度适中,蛋白表达(角蛋白 5&6、桥粒芯糖蛋白 1、兜甲蛋白和钙黏蛋白)适当。特别是,基于 HT 的配方被发现可刺激细胞增殖,这表现为 Ki67 表达显著增加,这表明修复机制的参与,增加上皮细胞的再生和分化,并改善表皮屏障作用。此外,基于 HT 的配方通过减少 RHE 组织中 IL-1α 和 IL-8 的释放显示出统计学上显著的抗炎活性,大于参考药物地塞米松。最后,发现 HT 的经皮吸收值非常好,证明了这种新配方如何增加生物活性化合物的可用性。

结论

鉴于这些结果,Fenolia® Eudermal Cream 15 可能是一种有效的治疗特应性皮炎的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ce4/6593001/32bffddab2b0/40199_2019_274_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ce4/6593001/32bffddab2b0/40199_2019_274_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ce4/6593001/32bffddab2b0/40199_2019_274_Figa_HTML.jpg

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