## 4 Grape Pomace Extracts and Their Bioactives as Ingredients in Sun Oils for Skin Care
### Grape Pomace--Phenolic Bioactive Ingredients  
Most studies focus on the concentrations of individual phenolics found in grapes, such as resveratrol, quercetin, and gallic acid, in terms of their activity against oxidative and inflammatory damage. However, it is worth mentioning that more and more new experimental data show that grapes, along with grape pomace extracts, are more effective than a single bioactive ingredient, as they interfere with more than one pathophysiological mechanism. Therefore, the different individual bioactive compounds contained in grape pomace are an excellent natural and effective solution for reducing chronic inflammation and oxidative stress. The use of grape stem extracts in cosmetics and more specifically in sunscreens is a promising venture. Based on recent research, these extracts have shown that they can combat skin aging, by reducing the appearance of wrinkles, fine lines, and age spots. Its action is mainly focused on neutralizing free radicals, which contribute to premature aging and skin deterioration, while improving skin elasticity and firmness. In addition, the phenolic compounds contained in grape pomace have significant anti-inflammatory action and are ideal for reactive, sensitive skin, as they help soothe the skin. Overall, grape pomace bioactives help achieve an even skin tone and protect against hyperpigmentation. Research based on the composition of grape pomace has shown that catechin, trans-resveratrol, quercetin, and viniferin are the phenolic compounds in the highest proportion in the extract [9]. Interestingly, most grape pomace bioactives are of an amphiphilic nature, according to the physicochemical properties of these molecules, as predicted by their structures and molecular weight using the quantitative structure-activity relationship (QSAR) in silico modeling approach (Figure 3). It should also be stressed that according to the Directive of the European Parliament and of the Council concerning the protection of animals used for scientific purposes, the number of experiments involving the use of animals needs to be reduced. The methods that can replace animal testing include computational prediction methods, including QSAR. These methods are designed to find a cohesive relationship between differences in the values of the properties of molecules and the biological activity of a series of test compounds. More specifically, QSAR models are used to predict biological activities and undesired effects of untested or novel compounds and to provide insight into relevant and consistent chemical properties or structural features that define biological activity. Figure 2: Illustration of different classes of phenolic bioactives of grape pomace [12]. One of the chemical properties of bioactives that can be predicted by QSAR is the determination of n-octanol/water partition coefficient (log Kow value), which is an index of their polarity and can be estimated based on the chemical structure of the target compounds. Thus, an insight of the behavior of the bioactives is given and the outcome can enhance further the research in the grape pomace bioactives and their functionality. As demonstrated in Figure 3, the majority of the bioactives found in grape pomace are semi-polar amphiphilic ones (log Kow values between 1 and 4). Only gallic acid and protocatechuric acid have polar behavior (log Kow < 1). This amphiphilic nature for these molecules is important, as it suggests that these molecules can surpass the external skin barrier of keratinocytes, as well as be diffused in the inner levels of the skin, including fibroblasts, where they can translocate from cell membranes to intracellular sites that facilitate their proposed skin protective properties, by being able to affect specific intracellular signaling pathways and gene expressions against oxidative stress, photoaging, and inflammation. Thus, phenolic compounds are a broad group of bioactive substances in grape stems that perform numerous tasks.