| In vitro: |
| J Agric Food Chem. 2014 Oct 1;62(39):9442-9. | | Myricetin prevents fibrillogenesis of hen egg white lysozyme.[Pubmed: 25196984] | Myricetin is a natural flavonol found in many grapes, berries, fruits, vegetables, and herbs as well as other plants. Recent studies have identified potential antiamyloidogenic activity for this compound. In this study, the kinetics of amyloid fibril formation by hen egg white lysozyme (HEWL) and the antifibril-forming activity of myricetin were investigated.
METHODS AND RESULTS:
We demonstrate that myricetin significantly inhibits the fibrillation of HEWL and the inhibitory effect is dose-dependent. Interestingly, the inhibitory effect toward HEWL fibrillation was stronger than that exerted by the previously characterized fibril-forming inhibitor quercetin, which has high structural similarity with myricetin.
CONCLUSIONS:
Spectrofluorometric and computational studies suggest that the mechanism underlying the inhibitory action of myricetin at a molecular level is to reduce the population of partially unfolded HEWL intermediates. This action is achieved by the tight binding of myricetin to the aggregation-prone region of the β-domain of HEWL and linking to the relatively stable α-domain, thus resulting in the inhibition of amyloid fibril formation. | | Tumour Biol. 2014 Dec;35(12):12583-92. | | Myricetin exerts anti-proliferative, anti-invasive, and pro-apoptotic effects on esophageal carcinoma EC9706 and KYSE30 cells via RSK2.[Pubmed: 25192723] | Myricetin, a common dietary flavonoid, is widely distributed in fruits and vegetables and is used as a health food supplement based on its anti-tumor properties. However, the effect and mechanisms of myricetin in esophageal carcinoma are not fully understood. Here, we demonstrated the effect of myricetin on the proliferation, apoptosis, and invasion of the esophageal carcinoma cell lines EC9706 and KYSE30 and explored the underlying mechanism and target protein(s) of myricetin.
METHODS AND RESULTS:
CCK-8 assay, transwell invasion assay, wound-healing assay, cell cycle analysis, and apoptosis assay were used to evaluate the effects of myricetin on cell proliferation, invasion, and apoptosis. Nude mouse tumor xenograft model was built to understand the interaction between myricetin and NTD RSK2. Pull-down assay was used to verify molecular mechanism. Myricetin inhibited proliferation and invasion and induced apoptosis of EC9706 and KYSE30 cells. Moreover, myricetin was shown to bind RSK2 through the NH2-terminal kinase domain. Finally, myricetin inhibited EC9706 and KYSE30 cell proliferation through Mad1 and induced cell apoptosis via Bad. Myricetin inhibits the proliferation and invasion and induces apoptosis in EC9706 and KYSE30 cells via RSK2. Myricetin exerts anti-proliferative, anti-invasive, and pro-apoptotic effects on esophageal carcinoma EC9706 and KYSE30 cells via RSK2.
CONCLUSIONS:
Our results provide novel insight into myricetin as a potential agent for the prevention and treatment of esophageal carcinoma. | | Biochem J. 2005 Mar 15;386(Pt 3):471-8. | | Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes.[Pubmed: 15469417] | The facilitative glucose transporter, GLUT4, mediates insulin-stimulated glucose uptake in adipocytes and muscles, and the participation of GLUT4 in the pathogenesis of various clinical conditions associated with obesity, visceral fat accumulation and insulin resistance has been proposed.
Glucose uptake by some members of the GLUT family, mainly GLUT1, is inhibited by flavonoids, the natural polyphenols present in fruits, vegetables and wine. Therefore it is of interest to establish if these polyphenolic compounds present in the diet, known to be effective antioxidants but also endowed with several other biological activities such as protein-tyrosine kinase inhibition, interfere with GLUT4 function.
METHODS AND RESULTS:
In the present study, we show that three flavonoids, quercetin, myricetin and catechin-gallate, inhibit the uptake of methylglucose by adipocytes over the concentration range of 10-100 microM. These three flavonoids show a competitive pattern of inhibition, with K(i)=16, 33.5 and 90 microM respectively. In contrast, neither catechin nor gallic acid inhibit methylglucose uptake. To obtain a better understanding of the interaction among GLUT4 and flavonoids, we have derived a GLUT4 three-dimensional molecular comparative model, using structural co-ordinates from a GLUT3 comparative model and a mechanosensitive ion channel [PDB (Protein Data Bank) code 1MSL] solved by X-ray diffraction.
CONCLUSIONS:
On the whole, the experimental evidence and computer simulation data favour a transport inhibition mechanism in which flavonoids and GLUT4 interact directly, rather than by a mechanism related to protein-tyrosine kinase and insulin signalling inhibition. Furthermore, the results suggest that GLUT transporters are involved in flavonoid incorporation into cells. | | Mol Med Rep . 2016 Mar;13(3):2094-100. | | Myricetin induces apoptosis via endoplasmic reticulum stress and DNA double-strand breaks in human ovarian cancer cells[Pubmed: 26782830] | | The mechanisms underlying myricetin-induced cancer cell apoptosis remain to be elucidated. Certain previous studies have shown that myricetin induces apoptosis through the mitochondrial pathway. Apoptosis, however, can also be induced by other classical pathways, including endoplasmic reticulum (ER) stress and DNA double‑strand breaks (DSBs). The aim of the present study was to assess whether these two apoptotic pathways are involved in myricetin‑induced cell death in SKOV3 ovarian cancer cells. The results revealed that treatment with myricetin inhibited viability of SKOV3 cells in a dose‑dependent manner. Myricetin induced nuclear chromatin condensation and fragmentation, and also upregulated the protein levels of active caspase 3 in a time‑dependent manner. In addition, myricetin upregulated ER stress‑associated proteins, glucose‑regulated protein‑78 and C/EBP homologous protein in SKOV3 cells. Phosphorylation of H2AX, a marker of DNA DSBs, was revealed to be upregulated in myricetin-treated cells. The data indicated that myricetin induces DNA DSBs and ER stress, which leads to apoptosis in SKOV3 cells. |
|
| In vivo: |
| Biochem Pharmacol. 2015 Jan 1;93(1):59-71. | | Myricetin prevents titanium particle-induced osteolysis in vivo and inhibits RANKL-induced osteoclastogenesis in vitro.[Pubmed: 25449599] | Titanium (Ti) particle-induced periprosthetic osteolysis and subsequent aseptic loosening are a primary reason for total hip arthroplasty failure. The aim of this study was to assess the effect of myricetin on Ti particle-induced osteolysis and osteoclastogenesis.
METHODS AND RESULTS:
We demonstrated that myricetin, a natural plant extract, exerts potent inhibitory effects on Ti particle-induced osteolysis in a mouse calvarial model. Further histological analysis indicated that the inhibition of osteoclast formation and function, and the secretion of inflammatory factors, are key targets for therapeutic agents in the treatment of wear particle-induced osteolysis. In vitro, we found that myricetin suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Moreover, myricetin significantly reduced the expression of osteoclast-specific markers in mouse bone marrow-derived macrophages, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, the calcitonin receptor, V-ATPase d2, c-fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that myricetin inhibited osteoclastogenesis through the suppression of the nuclear factor-κB (NF-κB) signaling pathway and mitogen-activated protein kinase (MAPK) pathways involving extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase 1/2 (JNK1/2). While, the inhibition of TNF-α and IL-1β secretion was another reason for the suppressive effect of myricetin on Ti particle-induced osteolysis.
CONCLUSIONS:
Collectively, these findings suggest that myricetin is a potential natural agent for the treatment of periprosthetic osteolysis and other osteoclast-related osteolytic diseases. |
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Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
