F biological effects induced by caffeic acid involves: enzyme3.two. Caffeic Acidactivity inhibition (5- and 12-lipoxygenases,

F biological effects induced by caffeic acid involves: enzyme3.two. Caffeic Acidactivity inhibition (5- and 12-lipoxygenases, glutathione Referance Inhibitors products S-transferase, xanthine oxidase), antitumor activity, anti-inflammatory properties, modulation of cellular response to ROS and inhibition of HIV replication [502]. Nardini et al. [50] reported that caffeic acid significantly inhibits Cer-induced activation of NF-B in human monocytic U937 cells, with consequent suppression of acute inflammation, septic shock, HIV replication, acute phase response, viral replication, radiation damage, atherogenesis and possibly some neoplastic degeneration. The NF-B inhibition mechanisms can be distinctive: countering the adjustments in the intracellular redox status induced by Cer, inhibition of five and 12 lipoxygenases activities or PKC and PKA activity arrest. Furthermore, some data indicate that caffeic acid inhibits protein tyrosine kinase activity [53,54]. This potential could possibly be the mechanism liable for the inhibition of Cer-induced apoptotic response in lieu of its antioxidant properties. This hypothesis was also in agreement with all the observation that no tested antioxidants inhibit DNA fragmentation and thus apoptosis. The action of caffeic acid is two-faced: it shows pro-apoptotic effects at high concentrations (200 ) and antiapoptotic ones at reduced levels explaining a conflicted array of activities [50]. At low concentrations, close to these expected in vivo, it mediates a double inhibition mechanism on Cer-induced NF-B activation and Cer-induced apoptosis by protein tyrosine kinase. Under this viewpoint, caffeic acid couldn’t be employed as a coadjuvant to chemotherapy in low concentrations because it reduces Cer-mediated apoptosis (Figure 3B).Nutrients 2018, 10,8 of3.three. CAPE Caffeic acid phenethyl ester (CAPE) or 2-phenylethyl (2E)-3-(3,4-dihydroxyphenyl)acrylate is actually a natural bioactive compound. It occurs in lots of plants along with the primary human source is propolis. Propolis is usually a resinous substance produced by honeybees mixing saliva, beeswax and exudate collected from botanical sources. CAPE is actually a cinnamic acid polyphenol characterized by a hydroxyl catechol ring. It has diverse biological activities on infections, oxidative anxiety, inflammation, cancer, diabetes, neurodegeneration and anxiety [55]. Tseng et al. [56] demonstrated that CAPE-induced apoptosis involves nSMase activation and accumulation of Cer in C6 glioma cells. CAPE modulates two parallel signaling pathways both leading to activation of caspase 3 as an ultimate effector of apoptosis. On a single hand CAPE increases nSMase activity triggering the activation of ERK/NGFR/NGF/JNK pathway and alternatively it causes an accumulation of Cer which initiates the p38 MAPK/p53/BAX signaling path. In ZEN-3862 Purity & Documentation addition to the apoptotic possible of CAPE in cancer cells a coherent manipulation of Cer levels may perhaps strengthen the efficacy of chemotherapy agents (Figure 3C). 3.4. Catechin The catechin family members presents two benzene rings and a 3-OH-dihydropyran heterocycle with two chiral centers on C2 and C3. Hence, it has 4 diastereoisomers: two in trans configuration referred to as catechin and two in cis configuration known as epicatechin. In plants they are usually conjugated with gallic acid. Epigallocatechin-3-gallate (EGCG) would be the most potent catechin with antioxidant properties and it is mainly present in green tea with each other with its associated compounds epicatechin [57]. High concentrations of catechin may be located in fresh tea leaves (Camellia si.