Efficient Extraction of Polyphenols from Hamamelis virginiana Bark and Leaves: A Design-of-Experiments Approach to Accelerated Solvent- and Ultrasound-Assisted Extraction

Hamamelis virginiana L. is a rich source of phenolic compounds with potential applications in pharmaceutical and cosmetic formulations. However, efficient recovery of these constituents depends strongly on the extraction technique and process conditions. The aim of this study was to optimize accelerated solvent extraction (ASE) and ultrasound-assisted extraction (UAE) of phenolic compounds from H. virginiana bark and leaves using a Design-of-Experiments (DoE) approach. The effects of solvent composition, extraction temperature, extraction technique, and number of extraction cycles were evaluated using total phenolic content (TPC), DPPH radical-scavenging activity, and selected phenolic constituents as response variables. The phytochemical profiles of the extracts were characterized by UHPLC-DAD-ESI/TOF-MS. The effects of the investigated extraction parameters differed among individual responses and between leaves and bark, with methanol concentration and the number of extraction cycles identified as particularly important factors. Multi-response optimization revealed matrix- and technique-dependent optimal extraction conditions. For leaves, the optimal conditions were 80 °C, 70.3% MeOH, and two cycles for ASE and 72 °C, 63.5% MeOH, and three cycles for UAE, whereas for bark they were 80 °C, 57.5% MeOH, and two cycles for ASE and 80 °C, 63.3% MeOH, and two cycles for UAE. Experimental validation showed generally good agreement between predicted and observed responses, with all but one experimental value falling within the corresponding 95% prediction intervals. These findings demonstrate that optimization of phenolic compound extraction from H. virginiana should account for both the plant matrix and the targeted chemical constituents and support the use of DoE as an effective approach for selecting ASE and UAE conditions.