Abstract
Inflammatory response represents one of the main mechanisms of healing and tissue function restoration. On the other hand, chronic inflammation leads to excessive secretion of pro-inflammatory cytokines involved in the onset of several diseases. Oxidative stress condition may contribute in worsening inflammatory state fall, increasing reactive oxygen species (ROS) production and cytokines release. Polyphenols can counteract inflammation and oxidative stress, modulating the release of toxic molecules and interacting with physiological defenses, such as cytochromes p450 enzymes. In this paper, we aimed at evaluating the anti-inflammatory properties of different concentrations of Myrtus communis L. pulp and seeds extracts, derived from liquor industrial production, on human fibroblasts. We determined ROS production after oxidative stress induction by H2O2 treatment, and the gene expression of different proinflammatory cytokines. We also analyzed the expression of CYP3A4 and CYP27B1 genes, in order to evaluate the capability of Myrtus polyphenols to influence the metabolic regulation of other molecules, including drugs, ROS, and vitamin D. Our results showed that Myrtus extracts exert a synergic effect with vitamin D in reducing inflammation and ROS production, protecting cells from oxidative stress damages. Moreover, the extracts modulate CYPs expression, preventing chronic inflammation and suggesting their use in development of new therapeutic formulations.
Highlights
Inflammation is a natural self-protecting mechanism developed by the organisms to remove harmful stimuli, such as damaged cells or pathogens, being the initial step of healing processesMolecules 2019, 24, 1515; doi:10.3390/molecules24081515 www.mdpi.com/journal/moleculesMolecules 2019, 24, 1515 and the restoration of tissue function [1]
reactive oxygen species (ROS) synthesis imbalance is involved in various skin disorders, including photosensitivity and other malignancies, starting from DNA damage events [45,46], which can be adjusted before the onset or during early phases by endogenous or external antioxidant supplements [47]
We show that polyphenols found in Myrtus extracts were able to reduce the amount of ROS generated in our model (Figure 1), significantly inhibiting the expression of pr-inflammatory cytokines (Figures 2 and 3)
Summary
Inflammation is a natural self-protecting mechanism developed by the organisms to remove harmful stimuli, such as damaged cells or pathogens, being the initial step of healing processesMolecules 2019, 24, 1515; doi:10.3390/molecules24081515 www.mdpi.com/journal/moleculesMolecules 2019, 24, 1515 and the restoration of tissue function [1]. Inflammation is a natural self-protecting mechanism developed by the organisms to remove harmful stimuli, such as damaged cells or pathogens, being the initial step of healing processes. Some pathologic conditions are related to inflammasomes dysregulation, inhibition of autophagy, or perturbations in ubiquitination [2,3]. The inflammasome is a multiprotein complex able to secrete proinflammatory cytokines, as Interleukin 1 beta (IL-1β) and Interleukin 18 (IL-18), upon activation by a stimulus, including for example UVB irradiations [8]. Cytokines production plays a key role in modulating the inflammatory response, especially during the acute phase [9,10]. During the different steps of the inflammatory response, other kind of cytokines, as tumor necrosis factor alpha (TNF-α), interleukin
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