## 4 Discussion  
The management and elimination of agricultural by-products remain significant challenges. Addressing food waste sustainably necessitates innovative extraction technologies that maximize waste vaporization while minimizing environmental [45]. Recent advancements in green extraction techniques have demonstrated enhanced efficiency in recovering polyphenols from plant by-products, supporting their application in functional formulations [46]. Among several raw materials, grape pomace, rich in bioactive compounds, presents a valuable resource for developing natural additives [47]. Within this context, the Naviglio(r) rapid solid-liquid dynamic extractor emerges as an advanced solid-liquid extraction technology, offering several advantages over existing extraction methods. Unlike many conventional techniques that rely on heating the extraction system to enhance extraction efficiency, the Naviglio extractor(r) operates at room or sub-room temperature, preventing thermal degradation of heat-sensitive compounds, and allowing the use of deionized water as a solvent. Moreover, it utilizes pressure increases in the extracting liquid applied to the solid matrix, which helps to reduce extraction times while simultaneously enhancing the efficiency of the extraction process [48]. In this study, Naviglio extractor(r) was employed to prepare a grape pomace extract, which was then utilized to produce a dextran-grape conjugate (PLG-GRAPE). The extraction of the grape pomace was performed using water as the solvent, making the entire process highly appealing as it avoids the use of organic solvents in the extraction stages, thus, ensuring an eco-friendly approach. Therefore, the primary objective of this study was to undertake a comparative analysis of dextran-polyphenol conjugates (PLG-GRAPE) and free grape pomace extract with regard to stability, bioactivity, diffusion, and sustainability. From the data obtained, the  
Figure 13: Evaluation of anti-age activity on full-thickness skin tissues through collagen type one quantification (**A**); elastin quantification (**B**) and hyaluronic acid dosage (**C**). Values are shown as mean \(\pm\) st. dev based on three replicates (* \(p<\) 0.05 \(t\)-test vs. negative control). total polyphenol content in our grape pomace extract (18.00 \(\pm\) 0.6 mg eq CA/g) aligns with values reported in studies employing conventional extraction techniques [49]  
Regarding antioxidant activity, the DPPH radical inhibition capacity (65.0 \(\pm\) 0.8%) of our grape pomace extract is consistent with previous findings on Vitis vinifera extracts [50]. Polypphenols, known for their potent free radical scavenging ability, play a crucial role in oxidative stress reduction [51]. Notably, PLG-GRAPE conjugates exhibited antioxidant activity (63.7 \(\pm\) 0.7% to 65.2 \(\pm\) 0.4%) comparable to the free extract, indicating that dextran conjugation preserved bioactivity. The protective effects of PLG-GRAPE against oxidative stress and inflammation were further confirmed through in vitro studies. Exposure to oxidative agents (e.g., UV radiation, pollutants) increased reactive oxygen species (ROS) levels, DNA damage markers (e.g., 8-OHdG, CPDs), and pro-inflammatory cytokines (IL-1\(\alpha\), TNF-\(\alpha\), IL-6, IL-12), leading to cellular senescence and extracellular matrix degradation [52]. Treatment with PLG-GRAPE significantly reduced ROS levels, preserved nuclear and mitochondrial DNA, and prevented CPD formation. Furthermore, PLG-GRAPE effectively reduced pro-inflammatory cytokines and cellular senescence markers (e.g., \(\beta\)-galactosidase, MMP-9), restoring extracellular matrix components, further supporting the therapeutic potential of polyphenol conjugates in dermatological applications [53, 54]. In terms of safety, PLG-GRAPE was confirmed as biocompatible through the Neutral Red Uptake test (ISO 10993-5:2009 [38]).