Keratinocytes Migration Promotion, Proliferation Induction, and Free Radical Injury Prevention by 3-Hydroxytirosol.

Mario Abate,Simona Pisanti,Rosanna Martinelli,Marianna Citro,Mariella Caputo

doi:10.3390/ijms22052438

Mario Abate, Simona Pisanti + Show 3 more

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https://doi.org/10.3390/ijms22052438

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Abstract

3-hydroxytyrosol (HT) is the main phenolic compound found in olive oil with known antioxidant, anti-inflammatory, and antimicrobial properties in several dermatological conditions, both when taken in the form of olive oil or pure in cosmeceutical formulations. To date, its direct effect on the wound healing process and the molecular mechanisms involved have not yet been elucidated. Thus, in the present study, we aimed to explore its effects in vitro in epidermal keratinocyte cultures focusing on the molecular mechanism implied. HT was able to induce keratinocyte proliferation in the low micromolar range, increasing the expression of cyclin dependent kinases fundamental for cell cycle progression such as CDK2 and CDK6. Furthermore, it increased cell migration through the activation of tissue remodeling factors such as matrix metalloproteinase-9 (MMP-9) protein. Then, we evaluated whether HT also showed antioxidant activity at this concentration range, protecting from H2O2-induced cytotoxicity. The HT prevented the activation of ATM serine/threonine kinase (ATM), Checkpoint kinase 1 (Chk1), Checkpoint kinase 2 (Chk2), and p53, reducing the number of apoptotic cells. Our study highlighted novel pharmacological properties of HT, providing the first evidence of its capability to induce keratinocyte migration and proliferation required for healing processes and re-epithelialization.

Highlights

Many beneficial properties have been attributed to the Mediterranean diet (MD) which, to date, represents the best diet for the prevention of numerous diseases
Scientific research has shown that the polyphenols contained in olive oil, the main source of fat at the base of MD, have excellent pharmacological-nutritional properties and it is thanks to these molecules that MD is so beneficial to health [9,10,11,12]
The continuous research conducted in this field has shown that this molecule has no undesirable effects even at high doses [18,19], so much so that the EFSA (European Food Safety Authority) recommends a daily intake of at least 5 mg of 3-hydroxytyrosol through extra virgin olive oil use at meals [20,21]

Summary

Introduction

Many beneficial properties have been attributed to the Mediterranean diet (MD) which, to date, represents the best diet for the prevention of numerous diseases. Scientific research has shown that the polyphenols contained in olive oil, the main source of fat at the base of MD, have excellent pharmacological-nutritional properties and it is thanks to these molecules that MD is so beneficial to health [9,10,11,12]. The continuous research conducted in this field has shown that this molecule has no undesirable effects even at high doses [18,19], so much so that the EFSA (European Food Safety Authority) recommends a daily intake of at least 5 mg of 3-hydroxytyrosol through extra virgin olive oil use at meals [20,21]

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