); [EMAIL_ADDRESS] (L.B)  
[PERSON]  
2 Human Nutrition Unit, Department of Food & Drug, University of Parma, 43125 Parma, Italy; [EMAIL_ADDRESS] (L.C. ); [EMAIL_ADDRESS] (L.C. ); [EMAIL_ADDRESS] (L.B)  
[PERSON]  
2 Human Nutrition Unit, Department of Food & Drug, University of Parma, 43125 Parma, Italy; [EMAIL_ADDRESS] (L.C. ); letizia.bresciani@unipr. acids, proteins, and carbohydrates, as well as secondary metabolites, including alkaloids, terpenes, and (poly)phenols [3,4]. The interplay among these components can result in a synergistic effect in the final product [5, 6, 7]. The reliability and consistency in the quality of herbal products are fundamental to their efficacy and safety [8]. Given the inherently variable and complex nature of plant-derived products, which often contain numerous biologically active components that are not fully identified, health-promoting outcomes and safety profiles can vary significantly among products, even within the same class. This underscores the need for standardized extraction processes to ensure consistent efficacy and safety of herbal products. _Verbascum_ species are used externally for wound desiccation, and as antiseptic, astringent, demulcent, emollient, narcotic, antimalarial agent, and for the treatment of inflammation, migraine, asthma, and spasmodic cough [9, 10, 11]. Among _Verbascum_ genus, _V. nigrum_ L., the black mullein or dark mullein, also exhibits spectorant, mucolytic, sudorific, sedative, and diuretic activities [12]. Traditionally, _Verbascum_ species contain different classes of biologically active compounds, including flavonoids, which may be responsible for its various health benefits [13,14]. Apigenin, one of the most abundant flavonoids in _Verbascum_ species, is reported to be a potent anti-inflammatory compound, which may explain the traditional use of _Verbascum_ as a herbal drug against inflammation. Verbascoside, a phenylethanolamine glycoside, exhibits strong antioxidant activity and has been identified as a major contributor to the antioxidant capacity of _Verbascum_ extracts [15,16]. In addition, verbascoside is a compound scarcely present in human diet, which makes it extremely interesting as a nutraceutical compound. For these reasons, different approaches are employed to extract and characterize the active molecules present within _V. nigrum_ targeting high extraction yields and efficacy [12,13,17,18]. Lignocellulolytic enzymes play a crucial role in breaking down the components of the plant cell wall, thereby releasing the active compounds contained within the cells. These enzymes are capable of degrading the major polymers in lignocellulosic, namely cellulose and hemicellulose [19], thereby increasing the bioaccessibility of plant bioactives and making them available for downstream applications. Enzymatic treatment is considered a 'green' technology because it avoids the use of harmful solvents and energy-intensive reaction conditions that are often associated with traditional chemical processes. Thus, the use of enzymes results in safer processes and more environmentally friendly products, which is particularly important in industries where the final products are intended for human consumption or contact, such as the food, cosmetics, and pharmaceutical sectors [20]. The aim of the present work was to develop and optimize a standard method for the extraction of (poly)phenolic compounds from _V. nigrum_ L. that entails both an enzymatic pretreatment and a solvent extraction. In addition, to explore the possibility of further improving the release of the phytocompounds, the enzymatic cocktail was optimized by studying the role of each enzyme and the potential synergies between them.