## 4 Discussion
The molecular functions elicited by EA include scavenging of free radicals, regulation of lipid metabolism, and inhibition of fibrogenesis response-mediating proteins. Moreover, it restrains hepatic viral replication, facilitates suppression of growth factors, regulates transcription factors, the expression of proinflammatory cytokines, and augments the liver immune response [47]. Lately, EA has sparked considerable interest as a potential chemotherapeutic compound as it can induce apoptosis and inhibit the proliferation of various types of cancer cells _in vitro_ and in vivo through the regulation of apoptosis and energy metabolism. However, EA does not have a single target of action, but has effects that are highly dependent on cell type and cell metabolism. This is because EA can be transported into the cell through multiple mechanisms that influence its intracellular accumulation, especially in tumor cells where the transporters are differentially expressed (organic anion transporters (OATP), SLC22A (OAT1 and OAT4) families, sodium-dependent glucose transporter (SGLT1)). Thus, the usefulness of this compound as a cancer therapeutic is limited [53]. EA reportedly acts as a scavenger for free radicals and prevents the OS-related induction of apoptosis [54]. Its antioxidant properties are exerted through the regulation of OS-related pathways, such as Nrf2, cyclooxygenase2, and NF-kB [55, 56, 57, 58], which result in higher expression and activity of endogenous antioxidants [59], and in the inhibition of NADPH oxidase activity and ROS generation [60, 61]. Moreover, it is reported to inhibit the proliferation of cervical cancer by regulating the expression of IGBPF7 in a dose-dependent manner [62]. Our current study proved that the ability of Cur to counteract DNA damage provoked by benzene is expressed for intermediate and prolonged times of exposure (60 and 90 min) on zebrafish blood cells _in vitro_. This could be explained by the fact that Cur exhibits poor bioavailability due to poor absorption [63]. The anti-inflammatory properties of Cur have been described as comparable as of steroidal and nonsteroidal drugs, by inhibiting inflammatory enzymes (cyclooxygenases, lipoxygenases, nitric oxide synthase) and production of cytokines [64, 65, 66, 67, 68]. Furthermore, Cur has been reported to reduce the activation of the NF-kB pathway, hyperactivated in conditions of OS, by inhibiting IKB kinase and downregulating the expression of other genes involved in this pathway [69]. Also, it regulates the expression of tumor necrosis factor (TNF), leading to reduced cell proliferation [70]. The mechanism of action of Cur depends both on its chemical structure characterized by the presence of functional antioxidant groups, such as \(\beta\)-diket groups, carbon-carbon double bonds and phenylic rings, and on its ability to stimulate the production of antioxidant enzymes. In fact, it is able to regulate the expression of transcription factors and antioxidant enzymes, such as heme oxygenase-1 (HO-1), factor 2 related to nuclear erythroid factor 2 (Nrf2), SOD and GSH), and inhibits cytokine production (interleukin-1\(\beta\) (IL-1\(\beta\)), tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)), interleukin 12 (IL-12)) [71]. Its antitumor action occurs through the regulation of caspases-3 and -4 activities, intracellular calcium ion, ATMlevels and cell cycle arrest in the G2/M phase, while the ability to protect the nervous system comes from its effect on Akt, Wnt/\(\beta\)catenin and A\(\beta\) peptide phosphorylation. Moreover, Cur prevents gastrointestinal diseases and supports cardio-protection by acting on Treg and PKC\(\delta\) cells and through the effect on DKK-3 [72]. Recently, a randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the effects of Cur in patients with non-alcoholic fatty liver disease [73]. Investigators observed no changes in 8-hydroxy-2\({}^{\prime}\)-deoxyguanosine (8-OHdG) levels, a DNA marker of OS [73].