# 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  & & & No data available for & Antioxidant [51,52]; type II \\  & & & myricetin-3-O-glucoside; & diabetes inhibitor [52]; \\  & & & in vitro evaluation in & skin anti-ageing [53], active \\  & Red & Red & human hepatic microsomes & topical anti-dandruff agent \\ Myricetin-3-O- & RC, B, CM, Mo, Ru, & 61.4–614.1 mg/kg & showed that myricetin & for hair scalp [54]; several \\ glycoside & TG, TC, TF, TN, T & extract, dry basis & non-competitively & combinations including \\  & White & White & inhibited human & myricetin derivatives were \\ C\({}_{21}\)H\({}_{20}\)O\({}_{13}\) & White & 111.4–850.1 mg/kg & cytochrome P450 & studied for managing \\  & CB, Cd, MF, MR, & extract, dry basis & (CYP3A4); inhibition & diabetes and metabolic \\  & Ra, Sa, V [41] & [41] & constant: 74.6 \(\pm\) 7.99 uM & disorders, treating sleeping \\  & & & (higher than & disorders, exercise \\  & & & physiologically relevant & performance \\  & & & concentration) [50] & improvement [49] \\ \hline  & & & & Antioxidant [55]; potential \\  & Red & & Cytotoxic to McCoy cell & anti-obesity effects have \\  & RC, B, CM, Mo, Ru, & Red & line for concentration & been observed, with \\  & TG, TC, TF, TN, T & 13,374.4–46,528.5 mg/kg & \(>\) 215.2 mg/mL [55]; effect & dose-dependent reductions \\  & TR, Bg & extract, dry basis & of 100 uM on cell viability & in triglyceride content and \\  & White & White & Whatn hepatocytes, rat & lipid accumulation in \\ C\({}_{21}\)H\({}_{20}\)O\({}_{12}\) & White & 10,129.9–28,831.1 mg/kg & hepatocytes and human & 3T3-L1 adipocyte cells [57]; \\  & CB, Cd, MF, MR, & extract, dry basis & lung cells showed less & cardiovascular disorder \\  & Ra, Sa, V, FP, Si & [41,44] & toxicity when compared to & preventative, \\  & & & sorafenib [56] & anti-inflammatory and \\  & & & & anticancer [58] \\ \hline  & & & & \\  & & & & \\  & Red & & negligible effects on & Hepatoprotective, \\  & RC, B, CM, Mo, Ru, & & pregnant rats, and, & neuroprotective, antiviral, \\  & TG, TC, TF, TN, T & & although being toxic to the & antifungal, antisteate, \\  & White & & kidneys with long-term & anti-inflammatory, \\  & CB, Cd, MF, MR, & & use, the damage is & antifibrotic, and \\  & Ra, Sa, V [41] & & reversible [59]; acute & anticancer [45] \\  & & & toxicity test: & \\  & & & LD50 \(>\) 5000 mg/kg [60] & \\ \hline  & & & & Antimicrobial and \\  & & & & antioxidant [46], \\  & & & therapeutic effects against \\  & Red & Red & multiple diseases (cancer, \\  & & & obesity, diabetes and \\  & RC, B, CM, Mo, Ru, & 2026.4–5508.5 mg/kg & diabetic complications, \\  & TG, TC, TF, TN, T & extract, dry basis & is ischemia/reperfusion \\  & White & White & injury, neuropathy, \\  & CB, Cd, MF, MR, & 1642.6–6203.8 mg/kg & respiratory diseases, \\  & Ra, Sa, V [41] & & osteoarthritis, osteoporosis, \\  & & & ulcerative colitis, mastitisti, \\  & & & and reproductive system \\  & & & diseases) [61] \\ \hline \end{tabular}
\end{table} 
Table 1: Flavonoids identified in Portuguese grapevine leaves. The hydroxycinnamic acid derivatives (Table 2), including _trans_-cafratic acid and coutaric acid, generally have higher concentrations in the leaves of red varieties [41]. According to Koriem (2020) [72], the antioxidant and anti-inflammatory effects of grape stem or juice are related to the content of _trans_-cafratic acid, which also possesses antimutagenic properties. This acid promotes a reduction in high blood glucose and high blood pressure, having potential use in the therapy of diabetes and hypertension. Coutaric acid, which has been the least studied to date, revealed significant antioxidant properties [73] and antimicrobial activity against _Staphylococcus epidermidis_[74]. The hydroxycinnamic acid derivatives _trans_-caffeoyl tartaric acid and _trans_-coumaroyl tartaric acid are very safe molecules, with no toxicity being ascribed to the latter.