## 6 Grape and Winery By-Products: Active Ingredients in Cosmeceuticals
### Antioxidant  
Many studies as demonstrated in Table 4, have shown that grape by-products contain large amounts of polyphenols, substances that act as powerful antioxidants [81; 82]. These antioxidant molecules play a key role in maintaining good skin condition and preventing many skin diseases and disorders. Their main protective mechanism lies in their ability to bind free radicals, which are responsible for cellular damage and the aging process. Through this mechanism, the antioxidants contained in grape by-products ensure the repair of DNA damage, the regulation of gene expression associated with cell proliferation, metabolism, and cell survival, and the enhancement of antioxidant defenses [83; 84]. Consequently, grape by-products are a natural source of antioxidants, making them ideal for use in cosmetic formulations. Their incorporation in cosmetic products not only provides a high added value, but also significantly enhances the effectiveness of these products in protecting the skin from oxidative stress, DNA damage, and premature aging. A recent study on phenolic extracts, but also on grape seed and seed kernel oils, through their interaction with the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), demonstrated their antioxidant capacity [85]. This ability is due to the efficiency of the transfer of a hydrogen atom from the hydroxyl group attached to their aromatic ring. This process helps to neutralize free radicals by breaking the chain of oxidative reactions. Phenolic extracts showed greater free radical inhibition than oils, since the antioxidant activity of the latter was due only to the presence of tocopherols and toctorienols. Also, the antioxidant activity of grape pomace extracts was higher than that of grape seed extracts, which can be explained due to the composition of grape pomace consisting of grape seeds and grape skin in addition to seeds [86]. The next step was to utilize such grape seed by-products for the preparation of a facial moisturizer base and nine formulations with extracts and/or oils with a composition of 0.1% [45]. These formulations were evaluated for stability gradually over 35 days and for lipid oxidation by measuring absorbance with a UV-Vis spectrophotometer, with the results being positive for the replacement of synthetic antioxidants in the cosmetic formulations with the extracts and oils of grape by-products [45]. Meanwhile, another study [87] investigated the efficacy and safety of grape pomace as an antioxidant raw material for cosme. Initially, HPLC analysis confirmed the presence of ellagic acid as a bioactive compound. Grap pomace extract was compared in terms of its ability to inhibit DPPH radical with the synthetic antioxidant butylated hydroxytoluene (BHT). The results showed that the extract exhibited higher antioxidant activity than BHT, but this difference was statistically insignificant. In addition, grape pomace extract was proven to be non-cytotoxic in a range of concentrations even under oxidative stress. These results were confirmed by scanning electron microscopy (SEM) [87]. The antioxidant activity of grape seed extracts from five different varieties (Marselan, Syrah, Obeidi, Asswad Karech, and Cabernet Franc) was evaluated in another study for incorporation into cosmetic creams [3]. After the extraction, which used glycerin as a base, the extracts were analyzed for their total phenolic content (TPC) using the Folin-Ciocalteu method. The results indicated higher levels of phenolic compounds in the extracts from the Marselan and Syrah varieties. Similarly, the proanthocyanidin content was assessed using the 4-dimethylaminocinnamaldehyde reaction. The phenolic compounds in each extract, including gallic acid, catechins, chlorogenic acid, caffeic acid, and p-coumaric acid, were identified and quantified using HPLC. Gallic acid, a well-known antioxidant [88], was found in high concentrations (883.05 \(\pm\) 98.59 \(\mu\)g/g of dry matter) in the extract of the Obeidi variety.