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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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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.

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

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Abbreviations

AD:

atopic dermatitis

HT:

hydroxytyrosol

PBS:

phosphate buffered saline

MTT:

thiazoyl blue tetrazolium bromide

RP-LC-DAD:

reverse phase-liquid chromatography-diode array detection

RHE:

reconstructed human epidermis

SMM:

skinethic maintenance medium

LPS:

lipopolysaccharides

H&E:

hematoxylin and eosin

RT:

room temperature

Papp :

apparent permeability coefficient

ANOVA:

one-way analysis of variance

SC:

stratum corneum

EVOO:

extra virgin olive oil

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Acknowledgements

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

Author information

Authors and Affiliations

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

    Antonella Smeriglio, Marcella Denaro & Domenico Trombetta

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

    Antonella Smeriglio & Marcella Denaro

  3. Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, GE, Italy

    Luca Mastracci & Federica Grillo

  4. IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa, GE, Italy

    Luca Mastracci & Federica Grillo

  5. Department of Earth, Environment and Life Sciences, University of Genoa, Corso Europa 26, 16132, Genoa, GE, Italy

    Laura Cornara

  6. Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Shahid Beheshti Boulevard, Kermanshah, 6715847141, Iran

    Samira Shirooie

  7. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Nosrati Alley, Sheikh Bahai South Avenue, Mollasadra St, Vanak Sq, Tehran, 1435916471, Iran

    Seyed Mohammad Nabavi

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  1. Antonella Smeriglio
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  2. Marcella Denaro
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  3. Luca Mastracci
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  4. Federica Grillo
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  5. Laura Cornara
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  8. Domenico Trombetta
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Contributions

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). https://doi.org/10.1007/s40199-019-00274-3

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