Myricetin: Difference between revisions

| Watchedfields = changed

| verifiedrevid = 442913173

| ImageAlt = Skeletal formula of myricetin

| ImageFile1 = Myricetin-3D-balls.png

| ImageAlt1 = Ball-and-stick model of the myricetin molecule

| IUPACName=3,3′,4′,5,5′,7-Hexahydroxyflavone

| SystematicName=3,5,7-Trihydroxy-2-(3,4,5-trihydroxyphenyl)-4''H''-1-benzopyran-4-one

|Section1={{Chembox Identifiers

| CASNo_Ref = {{cascite}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 76XC01FTOJ

| PubChem=5281672

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB02375

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 18152

| EINECS = 208-463-2

| KEGG = C10107

| SMILES = Oc1cc(O)c2c(=O)c(O)c(oc2c1)c3cc(O)c(O)c(O)c3

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4444991

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|Section2={{Chembox Properties

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| HPhrases = {{H-phrases|315|319|335}}

| PPhrases = {{P-phrases|261|264|271|280|302+352|304+340|305+351+338|312|321|332+313|337+313|362|403+233|405|501}}

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'''Myricetin''' is a member of the [[flavonoid]] class of polyphenolic compounds, with antioxidant properties.<ref name="Ong"/> Common dietary sources<ref>{{Cite journal|last1=Holland|first1=Thomas M.|last2=Agarwal|first2=Puja|last3=Wang|first3=Yamin|last4=Leurgans|first4=Sue E.|last5=Bennett|first5=David A.|last6=Booth|first6=Sarah L.|last7=Morris|first7=Martha Clare|author-link7=Martha Clare Morris|date=2020-01-29|title=Dietary flavonols and risk of Alzheimer dementia|journal=Neurology|language=en|volume=94|issue=16|pages=e1749–e1756|doi=10.1212/WNL.0000000000008981|issn=0028-3878|pmc=7282875|pmid=31996451}}</ref> include vegetables (including [[tomato]]es), fruits (including [[Orange (fruit)|oranges]]), nuts, berries, tea,<ref name="Ross">{{cite journal |vauthors=Ross JA, Kasum CM | title = Dietary Flavonoids: Bioavailability, Metabolic Effects, and Safety | journal = Annual Review of Nutrition | volume= 22 | pages= 19–34 | date= July 2002|pmid=12055336 |doi= 10.1146/annurev.nutr.22.111401.144957 }}</ref> and red wine.<ref>{{cite journal |vauthors=Basli A, Soulet S, Chaher N, Merillon JM, Chibane M, Monti JP, Richard T |title=Wine polyphenols: potential agents in neuroprotection |journal=Oxidative Medicine and Cellular Longevity |pages=805762|date= July 2012 |doi=10.1155/2012/805762 |pmid= 22829964 |pmc=3399511 |volume=2012|doi-access=free }}</ref>

Myricetin is structurally similar to [[fisetin]], [[luteolin]], and [[quercetin]] and is reported to have many of the same functions as these other members of the [[flavonol]] class of flavonoids.<ref name="Ross" /> Reported average intake of myricetin per day varies depending on diet, but has been shown in the Netherlands to average 23&nbsp;mg/day.<ref>{{cite journal |vauthors=Hollman PC, Katan MB |title=Health effects and bioavailability of dietary flavonols |journal=Free Radical Research |pages=Suppl S75–80 |date= Dec 1999 |pmid= 10694044 |volume=31 Suppl |doi=10.1080/10715769900301351}}</ref>

Myricetin is produced from the parent compound [[taxifolin]] through the [[ampelopsin|(+)-dihydromyricetin]] intermediate and can be further processed to form [[laricitrin]] and then [[syringetin]], both members of the flavonol class of flavonoids.<ref name="Flamini">{{cite journal |vauthors=Flamini R, Mattivi F, De Rosso M, Arapitas P, Bavaresco L |title=Advanced knowledge of three important classes of grape phenolics: anthocyanins, stilbenes and flavonols |journal=International Journal of Molecular Sciences|pages=19651–69 |date= Sep 2013 |pmid= 24084717 |pmc=3821578 |doi=10.3390/ijms141019651 |volume=14 |issue=10|doi-access=free }}</ref> Dihydromyricetin is frequently sold as a supplement and has controversial function as a partial [[GABAA receptor|GABA_A receptor]] potentiator and treatment in [[Alcoholism|Alcohol Use Disorder (AUD)]]. Myricetin can alternatively be produced directly from [[kaempferol]], which is another flavonol.<ref name="Flamini"/>

== Sources ==

{| class="wikitable sortable"

!Foods

! data-sort-type="number" |Myricetin

<small>(mg/100g)</small>

|-

|[[carob]] fiber

|48<ref name="usda">{{cite web|url=http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/Flav/Flav_R03.pdf|title=USDA Database for the Flavonoid Content of Selected Foods, Release 3|year=2011|publisher=U.S. Department of Agriculture}}</ref>

|-

|[[fennel]] leaves, raw

|20<ref name="usda" />

|-

|[[parsley]], fresh

|15<ref name="usda" />

|-

|[[Goji|goji berry]], dried

|11<ref name="usda" />

|-

|[[Vaccinium uliginosum|bog blueberry]], frozen

|7<ref name="usda" />

|-

|[[carob]] flour

|7<ref name="usda" />

|-

|[[cranberry]]

|7<ref name="usda" />

|-

|[[Rumex|dock]], raw

|6<ref name="usda" />

|-

|[[Blackcurrant|European black currant]], raw

|6<ref name="usda" />

|-

|[[Empetrum nigrum|crowberry]]

|5<ref name="usda" />

|-

|[[Vaccinium virgatum|rabbit-eye blueberry]], raw

|5<ref name="usda" />

|-

|[[sweet potato]] leaves, raw

|4<ref name="usda" />

|}

== Oxidative Properties ==

=== 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 [[chelating agent|chelate]] intracellular transition metal ions that ultimately produce ROS.<ref name="Ross" />

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.<ref name="Ross" />

=== 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 {{Citation needed|date=November 2021}}. It has been seen that when in the presence of cyanide, autoxidation is favored, resulting in superoxide, a byproduct characteristic of causing cellular damage {{Citation needed|date=November 2021}}. However, sodium azide, [[superoxide dismutase]], and [[catalase]] have been seen to inhibit the autoxidation of myricetin.<ref name="Ong"/>

Myricetin may also act as a pro-oxidant in its ability to increase the production of [[hydroxy radical]]s through reactions with Fe²⁺ or Fe³⁺−[[EDTA]] and [[hydrogen peroxide]]{{Citation needed|date=November 2021}}. 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.<ref name="Ong"/>

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.<ref name="Ong"/>

==Potential health effects==

{{more medical citations needed|section|date=May 2018}}

===Anticarcinogen===

Myricetin is also effective in protecting cells from [[carcinogen]]ic 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 medication|topical]] application of myricetin to mice inhibited the binding of benzo(a)pyrenes to DNA and protein native to epidermal skin cells.<ref name="Ong"/>

Myricetin also has been shown to inhibit the act of genetic mutation as exhibited by the [[Ames test]]. This test showed that myricetin was more effective in preventing mutagenesis initiated by certain carcinogenic polycyclic aromatic hydrocarbons (benzo(a)pyrene, dibenzo(a,h)pyrene, and dibenzo(a,i)pyrene) as compared to others in which it was less effective in preventing against mutagenesis (benzo(a)pyrene 4, 5-oxide and the bay-region diol-epoxides of benzo(a)anthracene, chrysene, and benzo(c)phenathrene).<ref name="Ong"/> This data shows that myricetin is not unilaterally able to reduce the carcinogenic activity of all polycyclic aromatic hydrocarbons or even the more specific subclass of benzo(a)pyrenes. Myricetin’s exact biochemical activity is still not fully understood. Clearly there is a multifaceted, complex system involved in the anticarcinogenic activity displayed by myricetin that does not apply equally to all carcinogens of the same subfamily.

===Mutagen===

It has also been shown that myricetin can itself act as an agent of mutagenicity. Myricetin can produce [[frameshift mutations]] in the genomes of particular strains of ''Salmonella typhimurium''.<ref name="Ong"/> In general, biochemical structural studies have shown that flavonoid structures can [[tautomer]]ize in biological systems to become active mutagens.<ref name="Ong"/>

===Interactions with DNA===

Myricetin can act as a [[pro-oxidant]] compound when it interacts with DNA. Studies involving ''in vitro'' models have shown that myricetin causes the degradation of DNA. Additionally, myricetin, in the presence of Fe³⁺ and Cu²⁺, intensified this DNA degradation. The antioxidants catalase, superoxide dismutase, mannitol, and sodium azide in combination with Cu²⁺ increased the DNA degradation activity of myricetin. Myricetin was shown to create [[reactive oxygen species]] that caused the DNA damage.<ref name="Ong"/>

It has been demonstrated that myricetin, depending on its concentration, displays different oxidizing effects on DNA. Polyphenols like myricetin are able to reduce (donate electrons to) Fe³⁺. Thus, this reaction yields a less oxidized (more reduced) form of the iron cation: Fe²⁺ and a less reduced (more oxidized) form of myricetin.<ref name="Ong"/> This allows myricetin to form a complex with oxygen and biochemically target the DNA molecule. At higher and higher concentrations of myricetin, the rate of DNA damage has been shown to decrease.<ref name="Ong">{{cite journal |vauthors=Ong KC, Khoo HE | title = Biological Effects of Myricetin | journal = General Pharmacology | volume = 29 | issue = 2 | pages = 121–126 | date= August 1997 | pmid= 9251891 | doi= 10.1016/S0306-3623(96)00421-1 }}</ref> A current hypothesis for why this occurs can be attributed to myricetin’s ability to [[chelating agent|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]].<ref name="Ong"/> Inhibition of cellular DNA polymerases could have dangerous effects on the cell’s ability to replicate its genome and its progression through the [[cell cycle]]. Inhibition of cellular RNA polymerase could have deleterious effects on the cell’s capacity to transcribe and translate DNA and RNA to produce vital proteins for the cell. Researchers have found that myricetin has the ability to interfere in the RNA polymerase pathway in two different ways. In [[Escherichia coli|''E. coli'']] myricetin competitively inhibited [[Guanosine triphosphate|GTP]] substrate binding to RNA polymerase. In T7 [[bacteriophages]] myricetin competitively inhibited DNA template binding to RNA polymerase.<ref name="Ong"/>

===Antiviral===

Myricetin has been seen to demonstrate antiviral activity against a number of viruses including [[murine leukemia virus|Moloney murine leukemia virus]], [[murine leukemia virus|Rauscher murine leukemia virus]], and the [[human immunodeficiency virus]]. Its effects against the proliferation of viruses is thought to be a consequence of myricetin’s ability to inhibit the proper functioning of [[reverse transcriptase]]. Myricetin was identified as a [[competitive inhibition|competitive inhibitor]] of the reverse transcriptase of Rauscher murine leukemia virus and a partial competitor with respect to the human immunodeficiency virus.<ref name="Ong"/> Investigations into the activity of the [[Subtypes of HIV|HIV-1 strain]] when introduced to myricetin suggest the antiviral effects are derived from the inhibition of HIV-1 [[integrase]], however, there are suspicions that the inhibition is non-specific.<ref>{{cite journal |vauthors=Cushnie T, Lamb A |title=Antimicrobial activity of flavonoids |journal=International Journal of Antimicrobial Agents |pages=343–356 |date= November 2005| pmid=16323269 |doi=10.1016/j.ijantimicag.2005.09.002 |volume=26 |issue=5|url=https://zenodo.org/record/1050327 |pmc=7127073 }}</ref> Structural analysis of myricetin and other flavonoids with observed antiviral effects indicate that the 3,4’ free hydroxyl groups likely are responsible for inhibition.<ref name="Ong"/>

===Antithrombotic===

[[Polyphenol]]s such as myricetin may prevent oxidative stress-induced [[platelet]] activation/aggregation. Thus, consumption of antioxidants may serve an anti-thrombotic function. In addition to offering protection by neutralizing peroxide radicals and effecting [[Thrombaxane|thromboxane]] production via the [[PTGS1]] pathway, polyphenols such as myricetin may target other platelet activation pathways, limiting fibrinogen’s ability to bind platelet surface receptors.<ref>{{cite journal |vauthors=Santhakumar AB, Bulmer AC, Singh I |title=A review of the mechanisms and effectiveness of dietary polyphenols in reducing oxidative stress and thrombotic risk |journal=Journal of Human Nutrition and Dietetics |pages=1–21 |date=November 2013|pmid= 24205990 |doi=10.1111/jhn.12177 |volume=27 |issue=1|hdl=10018/1029016 |hdl-access=free }}</ref>

===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.<ref name="Ong"/><ref name="Minireview">{{cite journal |vauthors=Li Y, Ding Y |title=Minireview: Therapeutic potential of myricetin in diabetes mellitus |journal=Food Science and Human Wellness |pages=19–25 |date=December 2012|doi=10.1016/j.fshw.2012.08.002 |volume=1|doi-access=free }}</ref> 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.<ref name="Minireview"/>

Although myricetin has not been concluded to have more than a neutral effect on humans, it has been used as a form of traditional medicine for diabetes in Northern Brazil and is hypothesized by the Finnish Mobile Clinic Health Examination Survey to potentially be correlated to the lower risk of [[Type 2 diabetes]] in individuals whose diets included higher than average amounts of myricetin. However, since studies in the United States, such as the Women's Health Study, do not confirm these results, there is doubt of whether or not the difference is risk can actually be accredited to myricetin and is not the result of the inability to fully control other variables such as racial background or inconsistencies in diet between participants.<ref name="Minireview"/>

There is also evidence indicating that other characteristics of myricetin, such as its effect against [[inflammation]], [[oxidative stress]], and [[hyperlipidemia]], may be helpful to reduce or even prevent other clinical issues which arise from [[diabetes mellitus]].<ref name="Minireview"/>

===Antiatherosclerotic===

Antioxidants, including flavonoids such as myricetin, are often touted to reduce the risk of [[atherosclerosis]], the hardening of arteries associated with high cholesterol. However, ''in vivo'' studies are lacking and ''in vitro'' studies are contradictory and do not support this claim. This claim is based on myricetin's proposed ability to increase LDL uptake by macrophages, which in theory would protect against atherosclerosis. This theoretical action of myricetin is not supported by experimental data.<ref>{{cite journal |author=Wedworth, SM |title=Dietary flavonoids in atherosclerosis prevention.|journal=Annals of Pharmacotherapy |pages=627–8 |date=1995|pmid= 7663037 |volume=29 |issue=6 |doi=10.1177/106002809502900614|s2cid=37311639}}</ref> 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.<ref>{{cite journal |vauthors=Berliner JA, Navab M, Fogelman AM |title=Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics |journal=Circulation |pages=2488–96 |date=1995|pmid= 7729036 | doi=10.1161/01.CIR.91.9.2488 |volume=91 |issue=9}}</ref>

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.<ref>{{cite journal |author=Rice, BH |title=Dairy and Cardiovascular Disease: A Review of Recent Observational Research|journal=Current Nutrition Reports |pages=130–138 |date=2014|pmid= 24818071 |pmc=4006120|doi=10.1007/s13668-014-0076-4 |volume=3 |issue=2}}</ref><ref>{{cite journal |author1=Kratz, M |author2=Baars, T |author3=Guyenet, S |title=The relationship between high-fat dairy consumption and obesity, cardiovascular, and metabolic disease|journal=European Journal of Nutrition |pages=1–24 |date=Feb 2013|pmid= 22810464 |doi=10.1007/s00394-012-0418-1 |volume=52 |issue=1|s2cid=1360916 }}</ref>

===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.<ref name="Dajas">{{cite journal |vauthors= Dajas F, Rivera-Megret, F | title = Neuroprotection by Flavonoids | journal = Brazilian Journal of Medical and Biological Research | volume = 36 | pages = 1613–1620 |date = December 2003 |pmid= 14666245 |doi= 10.1590/S0100-879X2003001200002 | issue=12| doi-access = free }}</ref>

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.<ref name="Dajas"/>

===Anti-inflammatory===

Myricetin, along with other lipoxygenase- and cyclooxygenase-blocker flavonoids are seen to have significant anti-inflammatory characteristics, demonstrated by their ability to reduce [[edemas]] caused by carrageenan and croton oil.<ref name="Ong"/> The anti-inflammatory nature of myricetin lies in its ability to inhibit the amplified production of [[cytokines]] that occurs during inflammation. Testing on various types of [[macrophage]] cells, including RAW264.7, as well as on human synovial [[sarcoma]] cells, demonstrated the inhibition of several kinds of cytokines, such as [[interleukin-12]] and [[IL1B|interleukin-1β]], through down-regulation of transcription factors and mediators involved in their production.<ref name="Minireview"/> Other studies suggest that myricetin's anti-inflammatory nature could also potentially be dependent upon interfering in inflammatory signal pathways by inhibiting various kinases and, consequently, the function of [[tumor necrosis factor alpha]].<ref name="Minireview"/><ref>{{cite journal |vauthors=Gupta SC, Tyagi AK, Deshmukh-Tasker P, Hinojosa M, Prasad S, Aggarwal BB |title= Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols| journal= Archives of Biochemistry and Biophysics |pages= 91–99 |date= October 2014 |pmid= 24946050 |doi= 10.1016/j.abb.2014.06.006 |volume=559}}</ref>

===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.<ref>{{cite journal|doi=10.3390/nu8020090|pmid = 26891321|pmc = 4772053|year = 2016|last1 = Semwal|first1 = D. K.|title = Myricetin: A Dietary Molecule with Diverse Biological Activities|journal = Nutrients|volume = 8|issue = 2|pages = 90|last2 = Semwal|first2 = R. B.|last3 = Combrinck|first3 = S.|last4 = Viljoen|first4 = A.| doi-access=free }}</ref>

=== Immunomodulatory activities ===

Myricetin's preclinical [[immunomodulatory]] properties are now becoming increasingly widely known.<ref>{{Cite journal |last1=Ghassemi-Rad |first1=Javad |last2=Maleki |first2=Mahdis |last3=Knickle |first3=Allison F. |last4=Hoskin |first4=David W. |date=2018-05-10 |title=Myricetin-induced oxidative stress suppresses murine T lymphocyte activation |url=http://dx.doi.org/10.1002/cbin.10977 |journal=Cell Biology International |volume=42 |issue=8 |pages=1069–1075 |doi=10.1002/cbin.10977 |pmid=29745443 |s2cid=13675528 |issn=1065-6995}}</ref> It was discovered that myricetin may prevent [[T-lymphocyte]] stimulation in a mouse model by binding to anti-CD3 and anti-CD28 [[Monoclonal antibody|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 {{chem2|H2O2}} production. Through the inhibition of NF-B binding activity, these natural compounds were reported to significantly reduce the [[Lipopolysaccharide|lipopolysaccharide (LPS)-induced]] interleukin (IL)-12 production in mouse main [[macrophage]]s as well as the RAW264.7 monocytic cell-line.<ref>{{Cite journal |last1=Kang |first1=Bok Yun |last2=Kim |first2=Seung Hyun |last3=Cho |first3=Daeho |last4=Kim |first4=Tae Sung |title=Inhibition of interleukin-12 production in mouse macrophagesvia decreased nuclear factor-κB DNA binding activity by myricetin, a naturally occurring flavonoid |url=http://dx.doi.org/10.1007/bf02977791 |journal=Archives of Pharmacal Research |year=2005 |volume=28 |issue=3 |pages=274–279 |doi=10.1007/bf02977791 |pmid=15832812 |s2cid=30554297 |issn=0253-6269}}</ref> Myricetin produced [[epithelial layer]] contractile reflexes in separate rat [[aortic ring]]s at a concentration of 50 M.<ref>{{Cite journal |last1=Jiménez |first1=Rosario |last2=Andriambeloson |first2=Emile |last3=Duarte |first3=Juan |last4=Andriantsitohaina |first4=Ramaroson |last5=Jiménez |first5=José |last6=Pérez-Vizcaino |first6=Francisco |last7=Zarzuelo |first7=Antonio |last8=Tamargo |first8=Juan |date=August 1999 |title=Involvement of thromboxane A₂in the endothelium-dependent contractions induced by myricetin in rat isolated aorta |journal=British Journal of Pharmacology |volume=127 |issue=7 |pages=1539–1544 |doi=10.1038/sj.bjp.0702694 |pmid=10455307 |pmc=1566141 |issn=0007-1188|doi-access=free }}</ref> This substance induces the synthesis of [[Cytosolic ciliogenesis|cytosolic]] unbound calcium in cultured [[Bovine somatotropin|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.<ref>{{Cite journal |last1=Cho |first1=Young-Chang |last2=Yoon |first2=Goo |last3=Lee |first3=Kwang Youl |last4=Choi |first4=Hyun Jin |last5=Kang |first5=Bok Yun |date=September 2007 |title=Inhibition of Interleukin-2 Production by Myricetin in Mouse EL-4 T Cells |url=http://dx.doi.org/10.1007/bf02980240 |journal=Archives of Pharmacal Research |volume=30 |issue=9 |pages=1075–1079 |doi=10.1007/bf02980240 |pmid=17958323 |s2cid=40028977 |issn=0253-6269}}</ref>

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[[Category:Aromatase inhibitors]]