Abstract
Psoriasis is a chronic cutaneous condition characterized by the release of pro-inflammatory mediators and oxidative stress. The reduction of these factors is currently the most effective strategy to inhibit the symptoms of pathology. Antioxidants from natural sources are increasingly used to improve skin conditions. Dried red leaves from grapevine (Vitis vinifera L., cv Teinturiers) showed anti-inflammatory and anti-bacterial activities, but their possible effects on keratinocytes have not been previously investigated. In this study we tested the ability of a water extract from grapevine leaves (VVWE) to inhibit inflammatory conditions in human keratinocytes (HaCaT cells), challenged with proinflammatory (tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS)) or prooxidant (ultraviolet B radiation (UVB) or H2O2) mediators. VVWE inhibited interleukin-8 (IL-8) secretion induced by proinflammatory stimuli, acting on the IL-8 promoter activity, but the effect was lower when prooxidant mediators were used. The effect was partly explained by the reduction of nuclear factor-κB (NF-κB)-driven transcription and nuclear translocation. Furthermore, vascular endothelial growth factor (VEGF) secretion, a regulator of angiogenesis, was inhibited by VVWE, but not matrix metalloproteinase-9 (MMP-9), a protease involved in matrix remodeling. VVWE, assayed on Franz diffusion cell system, showed a marked reduction of High Performance Liquid Chromatography (HPLC)-identified compounds. Pure molecules individually failed to reduce TNF-α-induced IL-8 release, suggesting synergistic effects or the presence of other bioactive compounds still unknown.
Highlights
The epidermis, the outermost part of the skin, is the first barrier between our organism and the environment, and this layer is mainly constituted by keratinocytes [1]
We have previously demonstrated that the water extract from Vitis vinifera leaves (VVWE) shows anti-inflammatory activity at the gastrointestinal level, acting on the nuclear factor-κB (NF-κB) pathway [30]
Fetal bovine serum (FBS), and disposable materials for cell culture were purchased by Euroclone (Euroclone S.p.A., Pero-Milan, Italy)
Summary
The epidermis, the outermost part of the skin, is the first barrier between our organism and the environment, and this layer is mainly constituted by keratinocytes [1]. Antioxidants 2019, 8, 134 an active role in skin’s defense but is relevant to the pathogenesis of chronic inflammatory skin diseases, such as psoriasis and atopic dermatitis [2]. NF-κB regulates the expression of several genes involved in skin inflammatory conditions, such as interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) in different cell types, including keratinocytes [11]. IL-8 is a potent chemokine involved in the recruitment of leukocytes [12] whereas VEGF, which is increased in psoriatic lesions [13], promotes the formation of the typical psoriatic microvasculature [14]
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