Myricetin

Antioxidant Antioxidants are molecules present in fruits and vegetables that have been demonstrated to protect against some forms of cancer and cardiovascular disease. Biomolecules and cell structures can experience oxidative stress due to the presence and activity of reactive oxygen species (ROS). ROS like •OH, •O2−, and H2O2 are produced during cellular metabolism processes (aerobic respiration). ROS can damage lipids, DNA, and proteins. Gradual but steady accretion of such damage can lead to the development of many diseases and conditions including thrombosis, diabetes, persistent inflammation, cancer, and atherosclerosis. Flavonoids including myricetin are able to scavenge for ROS and can chelate intracellular transition metal ions that ultimately produce ROS. Myricetin also enhances the effects of other antioxidants. Myricetin can induce the enzyme glutathione S-transferase (GST). GST has been suggested to protect cells against oxidative stress by protecting cells against free-radicals. In vitro studies have shown that myricetin significantly increased GST activity. Pro-oxidant Multiple studies have demonstrated that myricetin also has the potential to act as a pro-oxidant due to its tendency to undergo autoxidation depending upon its environment . It has been seen that when in the presence of cyanide, autoxidation is favored, resulting in superoxide, a byproduct characteristic of causing cellular damage . However, sodium azide, superoxide dismutase, and catalase have been seen to inhibit the autoxidation of myricetin. Myricetin may also act as a pro-oxidant in its ability to increase the production of hydroxy radicals through reactions with Fe2+ or Fe3+−EDTA and hydrogen peroxide. The resulting hydroxy radicals are often linked to DNA degradation, however, there are doubts as to whether or not this damage would be significant when analyzed in vivo since in vitro studies with both bovine and human serum albumin exhibited extensive protection against it. Myricetin's pro-oxidative capabilities can also be seen in its ability to act as an inhibitory agent against glutathione reductase, which is responsible for regenerating glutathione, a scavenger of free radicals and peroxides. ==Potential health effects==

Anticarcinogen Myricetin is also effective in protecting cells from carcinogenic mutation. Myricetin reduces the risk of skin tumorigenicity that is caused by polycyclic aromatic hydrocarbons like benzo(a)pyrene, a highly carcinogenic compound. Myricetin provided protection against the formation of skin tumors in mice models after tumor initiating and tumor promoter agents were applied to the skin. On a more biochemical level, it was shown that topical application of myricetin to mice inhibited the binding of benzo(a)pyrenes to DNA and protein native to epidermal skin cells. A current hypothesis for why this occurs can be attributed to myricetin's ability to chelate iron (Fe) (myricetin ligand forms two or more coordinate bonds to iron). These in vitro studies cannot be correlated directly to human models and should not be extrapolated. Myricetin also impacts the biochemical efficacy and binding ability of large intracellular biomolecules. Myricetin has been shown to inhibit viral reverse transcriptase, cellular DNA polymerase, and cellular RNA polymerase. Structural analysis of myricetin and other flavonoids with observed antiviral effects indicate that the 3,4' free hydroxyl groups likely are responsible for inhibition. Antidiabetic Several in vitro and animal studies have indicated the antidiabetic capabilities of myricetin; however, the evidence in clinical trials is less convincing. The flavonoid has been demonstrated to have a hypoglycemic effect by increasing the ability of adipocytes, as well as cells of the soleus muscle and liver of rats, to uptake glucose. This insulinomimetic effect is hypothesized to be a consequence of myricetin's either direct or indirect interaction with GLUT4, however, no analysis has produced concrete conclusions detailing exactly from where this effect is derived. In the hepatocytes of rats suffering from diabetes, myricetin has been observed to increase the activity of glycogen synthase 1. In trials done on Xenopus laevis oocytes, myricetin is thought to regulate the transport of glucose and fructose through the function of glucose transporter 2 (GLUT2) in sugar absorption. In addition, daily injections of myricetin into rats has been seen to be correlated with increased sensitivity to insulin, indicating the possibility of using a myricetin as treatment or protection against insulin resistance, a frequent cause of diabetes mellitus. In the mouse myoblast cell line known as C2C12, treatment with myricetin not only increased glucose uptake, but also enhanced lipogenesis, a result not seen from any of the other bioflavonoids tested. It is also proposed that myricetin may have the ability as a potent flavonoid antioxidant to prevent LDL oxidation, thus slowing the body's local inflammatory response and delaying the appearance of the first fatty streak and onset of atherosclerosis. Although mechanisms relating to myricetin specifically have not been proven, a diet that is rich in fruits and vegetables, and therefore rich in antioxidants, correlates with a decreased risk of cardiovascular disease, including atherosclerosis. Neuroprotectant It has also been shown that myricetin is effective in protecting neurons against oxidative stressors. Researchers have shown that PC12 cells treated with hydrogen peroxide (H2O2) as an oxidative stressor experience cell death due to apoptosis. When treated with myricetin, these oxidatively stressed cells displayed statistically significant increased cell survival. It has been suggested that myricetin not only has oxygen radical scavenging abilities, but also inherent, specific cell-survival capacities. Other molecules known for oxygen radical scavenging (vitamin E and boldine) did not successfully protect the cell models from oxidative stress and eventual cell death as effectively as myricetin and other biochemically related molecules. Anti-platelet aggregation activity Exposure to myricetin caused inhibition of rabbit platelet aggregation, induced by adenosine diphosphate, arachidonic acid, collagen and platelet activating factor (PAF). It inhibited specific receptor binding of PAF in rabbit platelets. The compound was found to be active against thrombin and neutrophil elastase. In addition, A prostacyclin-stimulated rise in the levels of platelet adenosine 3',5'-cyclic monophosphate (cAMP) was stimulated by myricetin. Immunomodulatory activities Myricetin's preclinical immunomodulatory properties are now becoming increasingly widely known. It was discovered that myricetin may prevent T-lymphocyte stimulation in a mouse model by binding to anti-CD3 and anti-CD28 monoclonal antibodies immobilised on beads. The inhibitory effect of myricetin on T cells, which was described in this study, was explained as being mediated via extracellular production. Through the inhibition of NF-B binding activity, these natural compounds were reported to significantly reduce the lipopolysaccharide (LPS)-induced interleukin (IL)-12 production in mouse main macrophages as well as the RAW264.7 monocytic cell-line. Myricetin produced epithelial layer contractile reflexes in separate rat aortic rings at a concentration of 50 M. This substance induces the synthesis of cytosolic unbound calcium in cultured bovine endothelial cells. Myricetin suppressed the release of IL-2 protein from mouse EL-4 T cells that had been stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin in a daily dosage approach. ==References==