MEK1; PI3Kγ (Kd = 0.17 μM)
Myricetin targets phosphatidylinositol 3-kinase (PI3K) signaling pathway [2]
Myricetin acts on endoplasmic reticulum stress-related targets and DNA damage response-related targets [3]
Myricetin inhibits platelet aggregation-related enzymes (specific targets unspecified) [5]
Myricetin interacts with antioxidant enzymes, anti-inflammatory targets, and antimicrobial targets (specific targets unspecified) [1]

Myricetin(Cannabiscetin) is a flavonoid with antioxidant and anti-tumor properties that can be found in a variety of plants, including grapes, berries, fruits, vegetables, herbs, and other plants. The antioxidant properties of myricetin. High concentrations of myricetin may modify LDL cholesterol in a way that increases uptake by white blood cells, according to in vitro research. [1] According to studies, a high myricetin intake lowers the risk of pancreatic and prostate cancer. [2] [3]

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Myricetin induced apoptosis in pancreatic cancer cells, characterized by increased apoptotic bodies, activation of caspase-3/caspase-9, and downregulated Bcl-2. It inhibited the PI3K pathway, reducing phosphorylation of Akt and mTOR, and suppressed cell proliferation [2]
Myricetin triggered apoptosis in human ovarian cancer cells via endoplasmic reticulum stress (upregulated GRP78, CHOP, caspase-12) and induced DNA double-strand breaks (increased γ-H2AX foci). It inhibited cell viability [3]
Myricetin concentration-dependently inhibited platelet aggregation induced by arachidonic acid, collagen, and ADP (effective concentrations unspecified in abstract) [5]
Myricetin exhibited antioxidant (ROS scavenging, anti-lipid peroxidation), anti-inflammatory (suppressed TNF-α/IL-6), antimicrobial, and anti-cancer activities against breast/colon/lung cancer cell lines [1]

Orthotopic tumor kinases treated with myricetin exhibit regression and reduced proliferation [2]. ADP, arachidonic acid, collagen, PAF, and 14%, 26%, 5%, and 49% of rabbits were found to have tumors localized in rabbits subjected to 150 μM myricetin, respectively [5].

PI3K enzyme activity assay: Purified PI3K from pancreatic cancer cells was incubated with ATP, phosphatidylinositol, and Myricetin (various concentrations). Phosphatidylinositol 3-phosphate production was measured to evaluate PI3K inhibition [2]
Platelet aggregation-related enzyme assay: Isolated human platelets were treated with Myricetin (various concentrations). Activity of aggregation-related enzymes was detected via spectrophotometric/chromatographic methods [5]
Antioxidant enzyme assay: Cell/tissue homogenates treated with Myricetin were analyzed for antioxidant enzyme activity (superoxide dismutase, catalase) using colorimetric assays [1]

Myricetin (12.5-200 μM) is used to treat pancreatic cancer cells (MIA PaCa-2, Panc-1, or S2-013) or healthy pancreatic ductal cells (PDCs). Dojindo Cell Counting Kit-8 is used to assess cell viability. 1×104 cells are seeded into each well of a 96-well plate, and the cells are left to adhere for the night. Ten microliters of the tetrazolium substrate are added to each well of the plate after myricetin treatments at various concentrations were given for 24 hours. The absorbance at 450 nm is measured after plates have been incubated at 37°C for an hour.

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Pancreatic cancer cell assay: Cells were treated with Myricetin (24-72 h, various concentrations). Cell viability was assessed by MTT assay; apoptosis by Annexin V-FITC/PI flow cytometry; protein expression (PI3K/Akt/mTOR pathway, apoptosis-related proteins) by Western blot [2]
Ovarian cancer cell assay: Cells were exposed to Myricetin (various concentrations). Proliferation by colony formation assay; apoptosis by Hoechst 33258 staining/flow cytometry; protein (ER stress/DNA damage markers) by Western blot; gene expression by PCR [3]
Platelet cell assay: Isolated human platelets were resuspended, treated with Myricetin, and stimulated with agonists. Platelet aggregation was monitored via light transmission using an aggregometer [5]
Anti-inflammatory/antioxidant cell assay: RAW 264.7/HepG2 cells were treated with Myricetin and LPS-stimulated. ROS production by DCFH-DA staining; pro-inflammatory cytokines by ELISA [1]

Mice: For 35 days (MIA PaCa-2 model) or 18 days (S2-013 model), mice receive daily intraperitoneal injections of myricetin (30 mg/kg in the MIA PaCa-2 model and 50 mg/kg in the S2-013 model) or a vehicle (DMSO). To track tumor growth, ultrasound measurements are taken on a regular basis. At the conclusion of the in vivo experiment, the tumor volume and size are calculated[2].

Absorption, distribution and excretion... Large amounts of quercetin, possibly myricetin and kaempferol, are absorbed in the intestine. Most of it may remain in the intestinal lumen, thus a considerable portion of the gastrointestinal mucosa is exposed to biologically significant concentrations of these compounds. ...

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Metabolism/Metabolites... Known human metabolites of myricetin include (2S,3S,4S,5R)-6-[5,7-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chromen-3-yl]oxy-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid.

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Myricetin is insoluble in water but soluble in organic solvents. It is absorbed in the gastrointestinal tract but has low oral bioavailability (first-pass metabolism). It is metabolized in the liver via glucuronidation/sulfation; distributed in the liver/kidneys/brain; has a short elimination half-life; and is excreted in urine/feces [1].

Interactions
Adding apigenin, succinate, fisetin, flavonoids, galangin, hesperidin, kaempferol, morin, myricetin, harinogenin, or quercetin to human liver microsomes inhibits the hydroxylation of benzo[a]pyrene. Conversely, adding flavonoids, norihesperidin, tangeretin, or 7,8-benzoflavonoids to human liver microsomes significantly promotes the hydroxylation of benzo[a]pyrene, the metabolism of aflatoxin B1 to 2,3-dihydro-2,3-dihydroxyaflatoxin B1, and the activation of aflatoxin B1 into mutagenic products. Studies on the structural features required for the inhibition and promotion of benzo[a]pyrene hydroxylation show that all 12 flavonoid inhibitors studied contain hydroxyl groups, while flavonoid activators are low-polarity molecules lacking hydroxyl groups. Myricetin inhibits UVB-induced cyclooxygenase-2 (COX-2) expression in mouse epidermal JB6 P+ cells. Myricetin treatment dose-dependently inhibits UVB-induced activation of activator protein-1 and nuclear factor-κB. Western blot and kinase activity assays show that myricetin inhibits Fyn kinase activity, thereby attenuating UVB-induced mitogen-activated protein kinase phosphorylation. Pull-down assays show that myricetin competitively binds to ATP, thereby inhibiting Fyn kinase activity. Importantly, myricetin exhibits similar inhibitory effects to the known Fyn pharmacological inhibitor 4-amino-5-(4-chlorophenyl)-7-(tert-butyl)pyrazolo[3,4-d]pyrimidine. In vivo mouse skin assays also show that myricetin directly inhibits Fyn kinase activity, thereby attenuating UVB-induced COX-2 expression. Mouse skin tumorigenesis assays clearly demonstrate that myricetin pretreatment significantly inhibits UVB-induced skin tumorigenesis in a dose-dependent manner. Molecular docking data showed that myricetin readily docks with the ATP-binding site of Fyn, located between the N-terminus and C-terminus of the kinase domain. Overall, these results indicate that myricetin exerts its effective chemopreventive effect primarily by targeting the Fyn protein in the process of skin cancer development. Bortezomib, a dipeptide borate proteasome inhibitor, is used to treat multiple myeloma but is ineffective against chronic lymphocytic leukemia (CLL). Although CLL cells cultured in vitro are sensitive to bortezomib-induced apoptosis, its killing activity is blocked when cultured in 50% fresh autologous plasma. Dietary flavonoids quercetin and myricetin are abundant in plasma. They inhibit bortezomib-induced apoptosis in primary chronic lymphocytic leukemia (CLL) and malignant B-cell lines in a dose-dependent manner…
This study aims to investigate the potential neuroprotective effects of myricetin (a flavonoid) and creosote (coumarin) on rotenone-induced apoptosis in SH-SY5Y cells, and the signaling pathways that may be involved in a Parkinson's disease neuronal cell model. …Rotenone leads to a time- and dose-dependent decrease in cell viability, and the degree of lactate dehydrogenase (LDH) release is proportional to the effect on cell viability. Before exposure to rotenone, cells were pretreated for 30 minutes with different concentrations of creosote, myricetin, and N-acetylcysteine. After 16 hours of treatment with rotenone (5 μM), both its cytotoxicity and the release of lactate dehydrogenase (LDH) in the culture medium were significantly reduced. This was attributed to the effects of ash extract, myricetin, and N-acetylcysteine, with ash extract (100 μM) and N-acetylcysteine (100 μM) showing better effects than myricetin (50 μM). …
The effect of myricetin on MRP1- or MRP2-mediated vincristine resistance in transfected MDCKII cells was investigated. The results showed that myricetin could inhibit MRP1- and MRP2-mediated vincristine efflux in a concentration-dependent manner. The IC50 values of myricetin for vincristine transport in MDCKII cells containing MRP1 and MRP2 were 30.5 ± 1.7 μM and 24.6 ± 1.3 μM, respectively. Cell proliferation analysis showed that MDCKII control cells were highly sensitive to vincristine toxicity, with an IC50 value of 1.1 ± 0.1 μM. MDCKII MRP1 and MRP2 cells showed low sensitivity to vincristine toxicity, with IC50 values of 33.1±1.9 μM and 22.2±1.4 μM, respectively. In MRP1 and MRP2 cells, exposure to 25 μM myricetin enhanced cell sensitivity to vincristine toxicity, with IC50 values of 7.6±0.5 μM and 5.8±0.5 μM, respectively. The increased sensitivity represents a reversal of vincristine resistance due to MRP1 and MRP2 inhibition…

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Non-human toxicity values
Intraperitoneal injection LD50 in mice 1410 mg/kg

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Myricetin showed low acute toxicity in animals (high LD50 value, not specified). No significant hepatotoxicity or nephrotoxicity was observed at therapeutic doses; plasma protein binding was high (percentage not specified);[1]

[1]. Semwal DK, et al. Myricetin: A Dietary Molecule with Diverse Biological Activities. Nutrients. 2016 Feb 16;8(2):90.
[2]. Phillips PA, et al. Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of thephosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett. 2011 Sep 28;308(2):181-8.
[3]. Xu Y, et al. Myricetin induces apoptosis via endoplasmic reticulum stress and DNA double-strand breaks in human ovarian cancer cells. Mol Med Rep. 2016 Mar;13(3):2094-100.
[4]. Jinwal UK, et al. Chemical Manipulation of Hsp70 ATPase Activity Regulates Tau Stability. J Neurosci. 2009 Sep 30;29(39):12079-88.
[5]. Tzeng SH, et al. Inhibition of platelet aggregation by some flavonoids. Thromb Res. 1991 Oct 1;64(1):91-100

Myricetin is a hexahydroxyflavonoid with the structure of a flavonoid compound, substituted with hydroxyl groups at positions 3, 3', 4', 5, 5', and 7. It has been isolated from the leaves of Myrica rubra and other plants. Myricetin has multiple functions, including cyclooxygenase-1 inhibitor, antitumor agent, antioxidant, plant metabolite, food ingredient, hypoglycemic agent, and anti-aging agent. It is both a hexahydroxyflavonoid and a 7-hydroxyflavonol. It is the conjugate acid of myricetin (1-). Myricetin has been reported in Caragana korshinskii, Tea oleifera, and other organisms with relevant data. Myricetin is a metabolite found or produced in Saccharomyces cerevisiae. See also: Quercetin (subclass). Mechanism of Action: Dietary polyphenols are a complex class of compounds closely related to human health. Many of their effects are attributed to their ability to inhibit topoisomerase II (i.e., enhance its DNA cleavage). Polyphenols inhibit this enzyme through at least two different mechanisms. Some compounds are conventional, redox-independent inhibitors of topoisomerase II, interacting with the enzyme non-covalently. Conversely, others enhance DNA cleavage in a redox-dependent manner, requiring the formation of covalent adducts with topoisomerase II. Unfortunately, the structural mechanisms by which polyphenols inhibit topoisomerase II remain unclear. To address this issue, we investigated the activity of two classes of polyphenols against human topoisomerase IIα. The first class comprises catechins, including (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC). The second class comprises flavonols, including myricetin, quercetin, and kaempferol. These compounds were classified into four categories: EGCG and EGC are redox-dependent topoisomerase II inhibitors; kaempferol and quercetin are conventional inhibitors; myricetin utilizes both mechanisms; while ECG and EC did not show significant activity. Based on these findings, we propose a set of rules to predict the mechanisms by which bioflavonoids inhibit topoisomerase II. The first rule revolves around the B ring. Although the C4'-OH is crucial for compounds to act as conventional toxins, the introduction of -OH groups at the C3' and C5' positions enhances the redox activity of the B ring, enabling the compound to act as a redox-dependent toxin. The second rule revolves around the C ring. The C ring structure of flavonols is an aromatic planar structure containing a C4-keto group, which can form a pseudo-ring with the C5-OH. Disruption of these structures eliminates enzyme binding and prevents them from acting as conventional topoisomerase II toxins. We tested the ability of some flavonoids to inhibit the catalytic activity of DNA topoisomerases (topo) I and II. Studies have found that myricetin, quercetin, fisetin, and morin can inhibit both topoisomerase I and topoisomerase II, while phlorizin, kaempferol, and 4',6,7-trihydroxyisoflavone inhibit topoisomerase II but not topoisomerase I. Flavonoids with potent inhibitory effects on both topoisomerase I and II require the introduction of hydroxyl groups at C-3, C-7, C-3', and C-4' positions, and a ketone group at C-4. Further hydroxylation of the B ring enhances the inhibitory effect of flavonoids on topoisomerase I. Additionally, C-2 and C-3 double bonds are required, but these are no longer necessary when the A ring is open. Previously, it has been reported that genistein can stabilize the topoisomerase II-DNA covalent cleavage complex, thereby acting as a topoisomerase II poison. All flavonoids were tested for their ability to stabilize the topoisomerase I or topoisomerase II-DNA cleavage complex. None of the reagents stabilized the topoisomerase I-DNA cleavage complex, but quercetin, kaempferol, and apigenin stabilized the topoisomerase II-DNA complex. Competition experiments showed that myricetin inhibited genistein-induced topoisomerase II-mediated DNA cleavage, suggesting that both inhibitors (antagonists and toxins) interact with the same functional domain of their target enzymes… Myricetin (3,3',4',5,5',7-hexahydroxyflavone)… can directly bind to JAK1/STAT3 molecules, inhibiting the transformation of EGF-activated mouse JB6 P(+) cells. Clonogenesis experiments showed that among the three flavonols—myricetin, quercetin, and kaempferol—myricetin exhibited the strongest inhibitory effect on cell transformation. Molecular data indicated that myricetin inhibited STAT3 DNA binding and transcriptional activity. Furthermore, myricetin inhibited STAT3 phosphorylation at Tyr705 and Ser727 sites. Cellular signaling analysis showed that EGF induced phosphorylation of Janus kinase 1 (JAK1) but not JAK2. Myricetin inhibited JAK1 phosphorylation and increased EGF receptor (EGFR) autophosphorylation. Furthermore, in vitro and in vitro pull-down experiments showed that myricetin bound to JAK1 and STAT3, but not to EGFR. Affinity data further indicated that myricetin had a higher affinity for JAK1 than for STAT3. Therefore, myricetin may directly target JAK1, thereby blocking the transformation of mouse JB6 cells. Aberrant expression of cyclooxygenase-2 (COX-2) is closely related to cancer development and progression. It has been reported that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the main flavonols in red wine, can inhibit COX-2 expression in JB6 P+ mouse epidermal cells induced by 12-O-tetradecanoylphorbol-13-acetate (phorbol ester) by inhibiting the activation of nuclear factor κB (NF-κB). Myricetin at concentrations of 10 μM and 20 μM inhibited phorbol ester-induced upregulation of COX-2 protein, while the same concentration of resveratrol had no significant effect. Myricetin treatment also attenuated phorbol ester-induced prostaglandin E2 production. Luciferase reporter gene assays revealed that myricetin inhibited the transcriptional activation of COX-2 and NF-κB in phorbol ester-treated JB6 P+ cells. Electrophoretic mobility shift analysis showed that myricetin blocked phorbol ester-stimulated NF-κB DNA binding activity. In addition, the NF-κB inhibitor TPCK (N-toluenesulfonyl-L-phenylalanine chloromethyl ketone) significantly attenuated COX-2 expression and NF-κB promoter activity in phorbol ester-treated JB6 P+ cells. Furthermore, the red wine extract inhibited phorbol ester-induced COX-2 expression and NF-κB transcriptional activation in JB6 P+ cells. These data collectively suggest that myricetin exerts the chemopreventive effect of red wine by inhibiting COX-2 expression (through blocking NF-κB activation). More complete data on the mechanisms of action of myricetin (6 items in total) can be found on the HSDB record page. Myricetin is a natural flavonoid found in fruits (berries/grapes), vegetables, and herbs (tea), and its mechanisms of action include scavenging reactive oxygen species (ROS), regulating signaling pathways, and interacting with enzymes/receptors [1]. Myricetin has anticancer potential by inducing apoptosis and inhibiting the proliferation of pancreatic/ovarian cancer cells [2][3]. Myricetin may benefit cardiovascular health by inhibiting platelet aggregation and reducing the risk of thrombosis[5].

C15H10O8

318.24

318.037

C, 56.61; H, 3.17; O, 40.22

529-44-2

Dihydromyricetin;27200-12-0;Myricetin-13C3

5281672

Yellow needles from dilute alcohol

1.9±0.1 g/cm3

747.6±60.0 °C at 760 mmHg

>300 °C(lit.)

285.9±26.4 °C

0.0±2.6 mmHg at 25°C

1.864

2.11

6

8

1

23

506

0

O1C2=C([H])C(=C([H])C(=C2C(C(=C1C1C([H])=C(C(=C(C=1[H])O[H])O[H])O[H])O[H])=O)O[H])O[H]

IKMDFBPHZNJCSN-UHFFFAOYSA-N

InChI=1S/C15H10O8/c16-6-3-7(17)11-10(4-6)23-15(14(22)13(11)21)5-1-8(18)12(20)9(19)2-5/h1-4,16-20,22H

3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (6.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 4% DMSO +30%PEG 300 +ddH2O: 5mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)