# Portuguese Grapevine Leaves: A Neglected By-Product with High Potential
### Grapevine Leaves  
According to the United Nations, the global population is on track to exceed 9.7 billion by 2050, implying that global food demand will rise even further. This will present various issues, as there will be a need to enhance and sustain food production to meet rapidly changing food demands while ensuring that environmental integrity and public health are not jeopardized. Wine by-products account for about 20 million tons of the entire quantity of vunified grapes, with the European Union accounting for 50% [20; 21; 22; 23], and have been used for a variety of applications, including agriculture, cosmetics [24], pharmaceuticals, biorefinery, animal feed, and the food sector [5]. Although GP and wine lees are the two most studied residues and contain important phytochemicals (phenolic compounds, primarily flavonoids, phenolic acids, and stilbenes) [25; 26], grapevine leaves are also a great source of bioactive substances, primarily phenolic substances, vitamins, fibers and minerals [27; 28; 29; 30; 31]. Vine leaves, which are part of the diet in some Mediterranean countries [10], are also used in traditional medicine, particularly in treating digestive pathologies, inflammations, and hemorrhages [32].  
Consistent with the French Pharmacopoeia, dried grapevine leaves contain up to 4% of total polyphenols and 0.2% of anthocyanins. Flavonoids are present in 3.5% in red leaves and from 4-5% in green leaves. According to Rana et al. (2022) [31] grapevine leaves contain considerable amounts of kaempfer-3-O-glucose, quercetin-3-O-glucoside, and glucuronides derivates, such as quercetin-3-O-\(\beta\)-D-glucuronide, isoquercetin, anthocyanin monomers, and dimers. These authors also reported gallic acid, stilbenes (resveratrol and viniferine), derivates of phenylacrylic acid (hydroxycinnamic and caffeoylquinic acids), with resveratrol being found specifically in stressed leaves. A study by Katalinic et al. (2009) [33] on grape leaf extracts demonstrated that they are rich in total phenolic compounds and that this abundance is influenced by the harvesting date of the leaves. These authors proved that the total phenolic content in leaf extracts collected in September was 339 mg gallic acid equivalent (GAE)/L, around 30% higher when compared to leaves collected in May (2911 mg GAE/L). This variation may be related to the substantial increase in total flavonoids, namely the catechin fraction. Guler and Camemir (2014) [34] investigated the total phenolic and flavonoid concentration of fresh leaves, which are a popular food in Turkey. These authors found a total phenolic level in fresh leaves ranging from 9.72-14.22 mg/g and a total flavonoid content ranging from 5.08-7.22 mg/g, with (+)-catechin, (-)-epicatechin, gallic acid, caffe acid and vanillic acid discovered in all fresh leaves.  
Recent research has indicated that the contents of polyphenols in red grapevine leaves are comparable to those determined in red grape and white grape seeds, and that leaves have antibacterial [35] and antioxidant [36] properties. Furthermore, grape leaf extracts demonstrated specific antiproliferative actions on cancer cells while having no comparable cytotoxic effects on healthy cells [37]. The therapeutic properties of wine, grapes, or their by-products are mainly related to polyphenolic compounds, which are secondary metabolites produced by plants. Vine leaves, often discarded by grape growers, are a rich source of polyphenols and other therapeutic compounds [38; 39; 40]. According to Sharafan et al. (2023) [24], antioxidant, anti-inflammatory, skin-whitening, and anti-aging properties of _V. vinifera_ extracts derive from their richness in phenolic and stilbenoid compounds. The bioactivity of leaves is largely attributed to compounds such as quercetin, caffe acid, kaempfer, resveratrol, and gallic acid, which provide a variety of benefits to human health, including antioxidant, anti-inflammatory, anti-obesity, anti-diabetic, and hepatotoxicity activities [14].