Polyphenolic Profile and Antioxidant Capacity of Coffee Silverskin Extracts: Insights from HPLC and GC-MS Analyses and Protective Effect in Schwann-like Cells

Coffee silverskin (CS) is an abundant leftover of the coffee roasting process known to contain significant concentrations of bioactive molecules, including polyphenols and flavonoids, with established antioxidant properties and potential applications in nutraceutical and functional-food formulations. This study systematically optimized extraction conditions to maximize the recovery of phenolics and antioxidants from CS by evaluating the effects of solvent type, temperature, and sonication time. Ethanol extraction at 20 °C for 30 min yielded the most enriched polyphenolic fraction, with the highest total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity across 2,2-diphenyl-1-picrylhydrazyl (DPPH), trolox equivalent antioxidant capacity (TEAC), and ferric reducing antioxidant power (FRAP) assays. Comprehensive chemical characterization via high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS) identified key phenolics (chlorogenic acid, hyperoside, quercetin), alongside abundant caffeine, tocopherols, and phytosterols. The biological relevance of the optimized extract was assessed for the first time in RT4-D6P2T Schwann-like cells, demonstrating significant cytoprotective and antioxidant effects against H2O2- and lipopolysaccharide-induced oxidative stress, thereby establishing a previously unreported neuroprotective potential.