## 3 Resveratrol and Free Radicals
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Direct Effect** & **Indirect Effect** & **Physiological Impact** & **Ref.** \\ \hline Inhibition of the dimerization of the ligand-AhR & & & [61] \\ complex, its binding to XRE sequences or the & & & [62] \\ recruitment of RNA polymerase II & & & \\ Inhibition of the PKC signal transduction pathway & Inhibition of COX-2 gene & & [63] \\ Increased TGF-\(\beta\)1 expression & & [64] \\ \hline PI3K/Akt mechanism activation & Phosphorylation of Nrf & & [65; 66] \\ Reduction of quinones to & & \\ \multirow{2}{*}{Activation of NQO1} & catechols and subsequent & Stimulation of the Nrf/ARE & \\  & inactivation by the COMT & pathway & [67; 68; 69] \\  & enzyme & & \\ \hline Increased concentration of PTEN & Upregulation of CAT and & Decreased concentration of & \\  & MrSOD mRNA levels & H\({}_{2}\)O\({}_{2}\) & [60; 71] \\ \hline Suppression of Akt phosphorylation & Inhibition of the & PI3K survival signaling & \\  & mTOR/p7056K pathway & pathway block & [72; 73] \\ \hline  & Inhibition of numerous & & \\ Inhibition of STAT3 and NF-kB & kinases (e.g., PKC, MAPK, & \\  & IKK) and some transcription & & [74; 80] \\  & factors (e.g., NF-kB, STAT3, & \\  & HIF-1\(\alpha\), and AP-1) & & \\  & Increased expression of I-kB\(\alpha\), & & \\ Inhibition of IKK & inactivation of NF-kB and its & & [76] \\  & retention in the cytoplasm & \\  & Suppression of cell & \\ Block of the activation of NF-kB induced by & proliferation, apoptosis, & \\ IL-1\(\beta\) and TNF-\(\alpha\) & angiogenesis, and formation & & \\  & of metastases & & \\ HDAC3/p300-mediated NF-kB signaling & Increased expression of PD-L1 & & [81] \\  & Enhanced binding of & \\ SIRT1 activation & \(\beta\)-catenin/TCF to PD-L1 & & [81] \\  & promoter & \\  & Enhanced anti-tumor T-cell & & [82] \\  & immunity & & \\ Inhibition of TGF-\(\beta\)1 activation & Inhibition of the EMT process & & [81] \\ \hline Reduced expression of PODD1, VEGF, and & Inhibition of anti-apoptotic & & \\ HIF-1\(\alpha\) & proteins and activation of & Reduced angiogenesis & [83; 84] \\  & pro-apoptotic ones & & \\ \hline  & Increased expression of & \\ Phosphorylation or acetylation of p53 at the level & pro-apoptotic proteins; & Induced arrest of the cell cycle & \\ of the serine residue 15 & activation of effector caspases & at the level of the G0/G1 and & \\  & and decreased expression of & S phase & \\  & anti-apoptotic proteins & & \\ \hline Phosphorylation of mTOR targets 4 EBP1 and & Reduction of cancer cells’ & & \\ P7056K & basal autophagy used to & Increased ROS production & [86] \\  & counteract their basal stress & & \\ \hline Inhibition of PI3K/Akt-mediated & Decreased phosphorylated & & \\ phosphorylation & levels of FoxO & & \\  & & & \\  & & \\ Increased SIRT1 expression and decreased & Reduction of the EMT & & \\  & & & \\  & & \\  & & & \\  & & \\  & & & \\ Deacetylation of the p65 subunit of the NF-kB & & Promotion of cell death & [89; 88] \\ complex & & & \\ \hline Increased FoxO & Increased SOD & Reduced oxidative stress & [81] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: _Cont._The antioxidant activity of resveratrol is linked to its ability to eliminate reactive oxygen species (ROS), especially superoxide (\(\bullet\)O\({}^{2-}\)), hydroxyl (OH\(\bullet\)), nitric oxide (NO), and peroxynitrite (ONOO\({}^{-}\)) radicals and all those radicals produced in metal-catalyzed reactions, such as the Fenton reaction [56; 57]. In addition, resveratrol has the ability to inhibit xanthine oxidase (XO), which is also responsible for the generation of superoxide radicals, through a non-competitive allosteric binding [58]. Furthermore, resveratrol exhibits protective effects against lipid peroxidation and oxidative damage to DNA resulting from the accumulation of ROS.