Antonella Smeriglio1,2, Marcella Denaro3,4, Luca Mastracci5,6, Federica Grillo5,6, Laura Cornara7, Samira Shirooie8, Seyed Mohammad Nabavi9, Domenico Trombetta3. 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. asmeriglio@unime.it. 2. Fondazione Prof. A. Imbesi, University of Messina, Piazza Pugliatti, 1, Messina, ME, Italy. asmeriglio@unime.it. 3. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Via Ferdinando Stagno d'Alcontres, 31, Viale SS. Annunziata, 98166, Messina, ME, Italy. 4. Fondazione Prof. A. Imbesi, University of Messina, Piazza Pugliatti, 1, Messina, ME, Italy. 5. Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, GE, Italy. 6. IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa, GE, Italy. 7. Department of Earth, Environment and Life Sciences, University of Genoa, Corso Europa 26, 16132, Genoa, GE, Italy. 8. Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Shahid Beheshti Boulevard, Kermanshah, 6715847141, Iran. 9. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Nosrati Alley, Sheikh Bahai South Avenue, Mollasadra St, Vanak Sq, Tehran, 1435916471, Iran.
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.
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.
Entities:
Keywords:
Anti-inflammatory effect; Atopic dermatitis; Histology and immunohistochemistry; Hydroxytyrosol; In vitro reconstructed human epidermis; Semi-solid formulation