Evaluation of Antioxidant and Wound-Healing Properties of EHO-85, a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract.

Antonio Casado-Diaz,Miriam Berenguer Pérez,José Luis Lázaro-Martínez,José Verdú-Soriano,Isaac Tunez,Manuel La Torre,José Manuel Moreno-Rojas,Feliciano Priego-Capote,Leocadio Rodríguez-Mañas,Gema Pereira-Caro

doi:10.3390/pharmaceutics14020349

Abstract

The excess of free radicals in the wound environment contributes to its stagnation during the inflammatory phase, favoring hard-to-heal wounds. Oxidative stress negatively affects cells and the extracellular matrix, hindering the healing process. In this study, we evaluated the antioxidant and wound-healing properties of a novel multifunctional amorphous hydrogel-containing Olea europaea leaf extract (OELE). Five assessments were performed: (i) phenolic compounds characterization in OELE; (ii) absolute antioxidant activity determination in OELE and hydrogel (EHO-85); (iii) antioxidant activity measurement of OELE and (iv) its protective effect on cell viability on human dermal fibroblasts (HDFs) and keratinocytes (HaCaT); and (v) EHO-85 wound-healing-capacity analysis on diabetic mice (db/db; BKS.Cg-m+/+Leprdb). The antioxidant activity of OELE was prominent: 2220, 1558, and 1969 µmol TE/g by DPPH, ABTS, and FRAP assays, respectively. Oxidative stress induced with H2O2 in HDFs and HaCaT was normalized, and their viability increased with OELE co-treatment, thus evidencing a protective role. EHO-85 produced an early and sustained wound-healing stimulating effect superior to controls in diabetic mice. This novel amorphous hydrogel presents an important ROS scavenger capacity due to the high phenolic content of OELE, which protects skin cells from oxidative stress and contributes to the physiological process of wound healing.

Highlights

The physiopathology of hard-to-heal wounds is linked to oxidation–reduction imbalance and inflammation pathway dysregulation [1]
Oxidative stress present in these wounds is due to excess levels of free radicals and reactive oxygen species (ROS), which are not adequately managed during the tissue repair process [2,3]
The objective of the present study was to evaluate the antioxidant and wound-healing properties of EHO-85, a novel multifunctional amorphous hydrogel in which Olea europaea leaf extract (OELE) was incorporated with the aim of removing excess ROS from the wound microenvironment to reduce oxidative stress and accelerate wound repair

Summary

Introduction

The physiopathology of hard-to-heal wounds is linked to oxidation–reduction (redox) imbalance and inflammation pathway dysregulation [1]. Oxidative stress present in these wounds is due to excess levels of free radicals and reactive oxygen species (ROS), which are not adequately managed during the tissue repair process [2,3]. These radicals are produced by the same inflammatory cells that come to the damaged area as a first-line antibacterial defense and as signaling molecules for the regulation and activation of healing [4,5]. The healing process slows down, resulting in a hard-to-heal wound [14,15]

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Conclusion