# Portuguese Grapevine Leaves: A Neglected By-Product with High Potential
## 2 Chemical Composition of Portuguese Grapevine Leaves
\begin{table}
\begin{tabular}{c c c c c} \hline
**Compound/Formula** & **Cultivar** & **Concentration** & **Toxicity** & **Bioactivity** \\ \hline  & & & & Anti-inflammatory [78; 80], cardiovascular \\ \(\alpha\)-linolenic acid & & & & protective, anti-cancer, \\ (C18:3) & Red & & & neuro-protective, \\ C\({}_{18}\)H\({}_{30}\)O\({}_{2}\) & B, T, TB, Ca [77] & 43.34–50.13 \(\mu\)g/g [77] & Nontoxic [78; 100] & anti-osteoporotic, \\  & & & & antioxidant [78], \\  & & & & antiungal [84; 101] \\ \hline  & & & Induces apoptosis and & \\  & & & necrosis in human & \\  & & & lymphocytes [102]; may & \\ Linoleic acid (C18:2) & Red & & & increase risk of \\ C\({}_{18}\)H\({}_{32}\)O\({}_{8}\) & B, T, TB, Ca [77] & 20.91–23.71 \(\mu\)g/ [77] & cardiovascular disease, & \\  & & & cancer, diabetes, & \\  & & & obesity, and & \\  & & & dementia [99] & \\ \hline  & & & Mice: toxic side effects & \\ Palmitic acid (16:0) & Red & & (damage glomeruli, \\ C\({}_{16}\)H\({}_{32}\)O\({}_{2}\) & B, T, TB, Ca [77] & 19.21–21.22 \(\mu\)g/g [77] & cardiomyocytes, and \\  & & & hepatocytes); promotes & \\  & & & growth of lung cancer & \\  & & & cells [98] & \\ \hline  & & & Induces apoptosis and & \\ Oleic acid (C18:1) & Red & & necrosis in human & \\ C\({}_{18}\)H\({}_{34}\)O\({}_{2}\) & B, T, TB, Ca [77] & 4.05–5.94 \(\mu\)g/g [77] & lymphocytes [102]; & \\  & & & very low acute oral & \\  & & & toxicity [103] & \\ \hline _trans_-hexadec-9- & & & & \\enoic acid (C16:1n-7) & Red & & & \\ C\({}_{16}\)H\({}_{30}\)O\({}_{2}\) & & & & \\ \hline  & & & & \\ \end{tabular}
\end{table} 
Table 3: Fatty acids identified in Portuguese grapevine leaves. antioxidant, anxiolytic, antidepressant, sedative, bronchodilatory and -protective, and hepato- and renal-protective benefits, among others [107; 108; 109; 110]. In addition to possessing some of these properties, \(\alpha\)-cedrol is antiseptic, antispasmodic, tonic, astringent, diuretic, insecticidal [111; 112], and stimulates collagen and elastin production [113]. Limonene is anti-inflammatory, antioxidant [114], anxiolytic [115], and antibacterial [116]; Z-citral works as an expectorant, appetite-stimulant, spasmolytic, anti-inflammatory, antiseptic, and antimicrobial [117]. The toxicity of terpen can vary widely depending on their specific chemical structure and concentration. Regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regulate the use of terpenoids in consumer products to ensure safety. Maximum allowable concentrations are often specified for various applications to prevent toxic effects. Some terpenoids can cause skin irritation or allergic reactions. For example, linalool and limonene, and their oxidized products, can be skin sensitizers [118]. Some terpenoids can be toxic if ingested in large amounts, although most of them are considered safe in the quantities usually found in plant species. A quantitative structure-activity relationship model to predict terpenoid toxicity using the Gram-negative bioluminescent Vibrio fischeri showed that, at a concentration of 1 uM, these compounds presented a toxicity level lower than 5%, except for citral and geranyl acetone. Furthermore, the standards tested exhibited a toxicity level higher than 30% at concentrations of 50-100 uM, except for valencene, eucalypt, and linalool oxide [119]. An acceptable daily intake of 0-0.5 mg/kg was established for citral, geranyl acetate, and linalool based on their perceptibly defined metabolism, fast excretion, and low toxicity in short-term studies [120]. The eucalypt acute oral LD50 in rats was reported to be between 1560 mg/kg and 2480 mg/kg. In rats, a lethal dose caused rapid cyanosis and stupor accompanied by irregular breathing, extreme sensitivity to noise, convulsions, and death from respiratory failure.