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

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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.


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.


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.


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.


In light of these results, Fenolia® Eudermal Cream 15 could be an effective agent to counteract atopic dermatitis.

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

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atopic dermatitis




phosphate buffered saline


thiazoyl blue tetrazolium bromide


reverse phase-liquid chromatography-diode array detection


reconstructed human epidermis


skinethic maintenance medium




hematoxylin and eosin


room temperature

Papp :

apparent permeability coefficient


one-way analysis of variance


stratum corneum


extra virgin olive oil


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The authors thank Simona Pigozzi and Ilaria Tosi for technical support.

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AS and DT designed this study and wrote the manuscript. AS, MD, LM, FG, performed the experiments. LC, SS, SMN and DT analyzed the data and carried out the statistical analysis. All authors read and approved the final manuscript.

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Correspondence to Antonella Smeriglio.

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Smeriglio, A., Denaro, M., Mastracci, L. et al. Safety and efficacy of hydroxytyrosol-based formulation on skin inflammation: in vitro evaluation on reconstructed human epidermis model. DARU J Pharm Sci 27, 283–293 (2019).

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