Vitis vinifera L. Leaf Extract Inhibits In Vitro Mediators of Inflammation and Oxidative Stress Involved in Inflammatory-Based Skin Diseases

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.

A Review of the Potential Benefits of Plants Producing Berries in Skin Disorders

“…The extract (1–50 μg/mL) inhibited IL-8 and VEGF release through NF-κB pathway, induced by TNF-α or LPS. The main phenols contained in leaves extract were quercetin glycosides and caftaric acid: they permeated ex vivo human skin (Franz cell test) ranging from 9 to 52 µg/g [ 95 ]. Similarly, Khanna et al [ 96 , 97 ], who investigated proanthocyanidin-rich grapevine seed extract, demonstrated that VEGF release induced by H 2 O 2 was inhibited.…”

Combined Extract of Vitis vinifera L. and Centella asiatica Synergistically Attenuates Oxidative Damage Induced by Hydrogen Peroxide in Human Umbilical Vein Endothelial Cells

“…Generally, the antioxidant activities of herbs are mainly associated with their phenolic and flavonoid compounds (Zheng and Wang, 2001). V. vinifera L. leaves contain various flavonoids, such as quercetin 3-glucuronide, quercetin 3-glucoside, kaempferol 3-glucoside, and cyanidin 3-glucoside (Sangiovanni et al, 2019). In addition, C. asiatica contains a variety of triterpenoids, such as asiaticoside, asiatic acid, madecassoside, and madecassic acid (Hashim et al, 2011).…”

“…Additionally, H 2 O 2 induces vascular permeability by upregulating VEGF, a vascular permeability factor and an endothelial cell-specific mitogen ( Chua et al, 1998 ; Lee et al, 2006 ). In recent studies, VE has been shown to counteract the release of VEGF induced by H 2 O 2 in human keratinocytes, and stem extracts have been shown to reduces levels of VEGF in human endothelial cells ( Stagos et al, 2014 ; Sangiovanni et al, 2019 ). In another study, the major compound of VE, quercetin 3-glucuronide, was shown to inhibit ROS generation and lipid peroxidation by increasing the activities of antioxidant enzymes, such as SOD and CAT, by upregulating heme oxygenase-1 via the transcription factors nuclear factor E2-related factor 2 and activator protein-1 ( Lee et al, 2017 ).…”

“…In previous studies, extracts of V. vinifera L. leaves have shown a hepatoprotective effect against carbon tetrachloride-induced acute liver damage and alcohol- induced oxidative damage in rats ( Karaman and Kocabas, 2001 ; Orhan et al, 2007 ; Pari and Suresh, 2008 ; Orhan et al, 2009 ). Recently, Sangiovanni et al (2019) also showed that V. vinifera L. leaf extracts (VE) with the highest quercetin 3-glucuronide content among phenols inhibits inflammation in human keratinocytes. In particular, the leaf extracts were shown to contain higher levels of total phenols and proanthocyanidins than stalk and marc extracts, and exhibited a greater effect on reducing intracellular ROS induced by H 2 O 2 in human dermal fibroblasts ( Puglisi et al, 2019 ).…”

Research Advances in the Use of Bioactive Compounds from Vitis vinifera By-Products in Oral Care

“…Due to their composition, the leaf extract can protect against the oxidation of emulsified linoleic acid and it displays a high free radical scavenging ability, high chelating activity on metal ions and high reducing power [ 147 ]. Recent research has shown the effect of grapevine leaves in NF-κB pathway inhibition through the reduction of nuclear factor-κB driven transcription and nuclear translocation in human gastric epithelial cells [ 148 ] and in human keratinocytes cell lines [ 149 ]. The anti-inflammatory activity of the V. vinifera leaves has also been tested in another in vitro study using human keratinocytes exposed to UV radiation.…”