## 7 The Role of Coumarins in the Nutraceutical Quality of Spirit Beverages  
Besides the contribution of coumarins to the sensory properties of spirit beverages according to the ageing conditions, they are involved in the nutraceutical component of these beverages' quality. Nutraceuticalul quality is related to the health benefits of foods and beverages [49; 221; 222; 223]. Indeed, moderate consumption of alcoholic beverages as part of a healthy lifestyle has been associated with lower cardiovascular risk compared to abstinence or heavy drinking [224]. The health benefits of moderate consumption of aged spirits can be assigned to their phenolic composition, which has remarkable biological functions, such as free-radical scavenging, inhibiting lipid peroxidation, and reducing platelet aggregation and thrombosis [225], in opposition to the ethanol-induced damage [6]. Concerning specifically the spirit beverages covered by this review, evidence exists for the relationship between the in vitro antioxidant properties and lignin-derived phenolic compounds extracted from wooden barrels to wine spirits [31; 53; 54; 55; 226], brandy [54; 56], whiskey [52] and rum [57]. In addition, the consumption of whiskey (100 mL/day) transiently increases the total phenolic content and enhances the plasma antioxidant capacity, thus potentially lowering the risk of coronary heart disease [227]. The work of [PERSON] et al. [228] revealed that compounds extracted from wooden barrels during the ageing of whiskey increased the cytoprotective protein, the enzyme heme oxygenase-1 (HO-1), in human endothelial cells, demonstrating that upregulation of HO-1 protein level might possibly contribute to the maintenance of blood vessel function. The health effects of phenolic compounds, and particularly those found in aged spirit beverages, depend on their chemical composition, their potential interactions with ethanol and the presence of other bioactive compounds [8]. Among them, phenolic aldehydes (such as sinapaldehyde, coniferaldehyde and vanillin), phenolic acids (such as vanillic acid and ellagic acid) and coumarins (such as aesculetin) identified in whiskey play an important role as antioxidants, and may partly contribute to the protection of blood vessels by triggering the activation of HO-1 gene [228; 229; 230]. Similar effects have been reported for wine spirit by [PERSON] et al. [231] and [PERSON] et al. [232]. Coumarins are nutraceuticalul compounds, due to their ability to exert non-covalent interactions with protein structures and free-radical scavenging activity [233; 234]; in general, they scavenge reactive oxygen species (ROS) via the hydrogen atom transfer mechanism or electron transfer to peroxyl radical [235]. The health effects of simple coumarins, most plentiful in wood and agedspirit beverages (as specified in Sections 4 and 6), have been thoroughly investigated in in vitro and in vivo studies, as shown in Table 8.  
Apart from the activities identified, the high bioavailability of coumarins is an essential feature to guarantee their biological effectiveness [117]. Actually, the oral intake does not result in complete uptake of bioactive compounds into the gastrointestinal tract, and a certain percentage is not absorbed [223]. Bioavailability includes bioaccessibility and bioactivity: bioaccessibility corresponds to the fraction of a compound released from the food matrix during the digestion process in the luminal content, being accessible for absorption in the small intestine or biotransformed by the gut microbiota; bioactivity includes the phenomena involving the absorbed compounds or their metabolites in the target tissue, resulting in biological activity on the body [275; 276]. However, in the light of current knowledge, compound concentrations cannot usually be determined directly at the site of action or target tissue.