Enhancing Effect of a Cysteinyl Thiol on the Antioxidant Activity of Flavonoids and Identification of the Antioxidative Thiol Adducts of Myricetin

Masuda, Toshiya; Miura, Yukari; Inai, Miyuki; Masuda, Akiko

doi:10.1271/bbb.130315

Cited by 17 publications

(12 citation statements)

References 26 publications

(28 reference statements)

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“…Likewise, all of the interactions herein described are non-covalent bonds, with hydrogen bonding constituting the vast majority of these, even though it is possible for myricetin to form adducts with thiols through carbons 2' and 6' on ring B (Masuda et al, 2013).…”

Section: Myricetin Is Predicted To Form Non-covalent Bonds Close To the Active Redox Sites Of Pdi And Erp5mentioning

confidence: 99%

Myricetin, the Main Flavonoid in Syzygium cumini Leaf, Is a Novel Inhibitor of Platelet Thiol Isomerases PDI and ERp5

et al. 2020

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Background: Flavonoids have been characterized as a prominent class of compounds to treat thrombotic diseases through the inhibition of thiol isomerases. Syzygium cumini is a flavonoid-rich medicinal plant that contains myricetin and gallic acid. Little is known about the potential antiplatelet properties of S. cumini and its constituent flavonoids.Objective: To evaluate the antiplatelet effects and mechanism of action of a polyphenolrich extract (PESc) from S. cumini leaf and its most prevalent polyphenols, myricetin and gallic acid.Methods: PESc, myricetin, and gallic acid were incubated with platelet-rich plasma and washed platelets to assess platelet aggregation and activation. In vitro platelet adhesion and thrombus formation as well as in vivo bleeding time were performed. Finally, myricetin was incubated with recombinant thiol isomerases to assess its potential to bind and inhibit these, while molecular docking studies predicted possible binding sites.Results: PESc decreased platelet activation and aggregation induced by different agonists. Myricetin exerted potent antiplatelet effects, whereas gallic acid did not. Myricetin reduced the ability of platelets to spread on collagen, form thrombi in vitro without affecting hemostasis in vivo. Fluorescence quenching studies suggested myricetin binds to different thiol isomerases with similar affinity, despite inhibiting only protein disulfide isomerase (PDI) and ERp5 reductase activities. Finally, molecular docking studies suggested myricetin formed non-covalent bonds with PDI and ERp5.Conclusions: PESc and its most abundant flavonoid myricetin strongly inhibit platelet function. Additionally, myricetin is a novel inhibitor of ERp5 and PDI, unveiling a new therapeutic perspective for the treatment of thrombotic disorders.

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Section: Myricetin Is Predicted To Form Non-covalent Bonds Close To the Active Redox Sites Of Pdi And Erp5mentioning

confidence: 99%

Myricetin, the Main Flavonoid in Syzygium cumini Leaf, Is a Novel Inhibitor of Platelet Thiol Isomerases PDI and ERp5

et al. 2020

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“…Geographically, it is distributed between 18 and 33º north latitude while its economic cultivation is mainly distributed in southeast coast regions, such as Zhejiang, Jiangsu, Fujian, Guangdong and Jiangxi Provinces. Myricetin, found in the bark of waxberry, is bitter in taste and warm in property with antiviral, anti-inflammatory, antioxidant, free radical scavaging, immune adjustment, anti-androgenic and antiallergic functions (11)(12)(13). In the present study, we examined the anticancer effects of myricetin.…”

Section: Introductionmentioning

confidence: 97%

Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway

Jiao

Zhang

2016

Oncology Reports

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As a main active compound in the bark of waxberry (Myrica rubra), myricetin is a macrocyclic diarylheptanoid, and can trigger the apoptosis of HeLa and PC3 cells. The aim of the present study was to elucidate the anticancer effect of myricetin on human breast cancer MCF-7 cells and to explore the possible mechanisms of action. MCF-7 cells were treated with different concentrations of myricetin (0-80 µM) for 12, 24 and 48 h. In the present study, we found that myricetin suppressed the cell viability of the MCF-7 cells at least partly through the induction of apoptosis as determined by MTT assay and flow cytometry. Western blot analysis revealed that myricetin effectively suppressed the protein expression of p21-activated kinase 1 (PAK1), MEK and phosphorylated extracellular mitogen-activated protein kinase (ERK1/2). In addition, treatment of myricetin activated glycogen synthase kinase-3β (GSK3β) and Bax protein expression, and inhibited β-catenin/cyclin D1/proliferating cell nuclear antigen (PCNA)/survivin and promoted caspase-3 activity in the MCF-7 cells. These results demonstrated that myricetin suppressed the cell viability of human breast cancer MCF-7 cells through PAK1/MEK/ERK/GSK3β/β-catenin/cyclin D1/PCNA/survivin/Bax-caspase-3 signaling.

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“…Additionally, by comparing myricetin with myricitrin, sugar moiety in the phytochemical weakens its inhibitory activity. Formerly, in a lipid oxidation system, myricetin and thiol conjugates were identified [33]. Recently, the conjugation (Δ316 Da) of one molecule of myricetin to M pro evaluated by intact MS has been reported [10], and the mechanism of conjugation of myricetin with protein thiol via the formation of oquinone is also proposed.…”

Section: Discussionmentioning

confidence: 99%

Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro

Kato

Higashiyama

Takaoka

et al. 2021

Preprint

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SARS-CoV-2 main protease is a possible target for protection against viral infection. This study examined the inhibitory effect of food phytochemicals on the main protease of SARS-CoV-2 by determining a cleaved product after chromatographic separation. First, 37 phytochemicals, including glycosides and metabolites, were screened at 20 µM; epigallocatechin gallate, myricetin, theaflavin, herbacetin, piceatannol, myricitrin, and isothiocyanates inhibited the enzyme in varying degrees. The IC50 values were estimated from 0.4 to 33.3 µM against the 0.5-µM enzyme. The dose-dependent adduction of epigallocatechin gallate and myricetin was confirmed by quinone staining of protein blotted onto a membrane. The enzyme activity was decreased by increasing the concentration of the two phytochemicals, accompanied by increasing the respective adducted molecule estimated by intact mass spectrometry. Reduced glutathione canceled the formation of conjugate and the inhibitory effect of epigallocatechin gallate or myricetin on the enzyme, suggesting that the formation of the quinone moiety in the phytochemicals is critical for the inhibition. The covalent binding of epigallocatechin gallate or myricetin to the cysteine residue at the active site was confirmed by analyzing peptides from the chymotrypsin-digested main protease.

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Enhancing Effect of a Cysteinyl Thiol on the Antioxidant Activity of Flavonoids and Identification of the Antioxidative Thiol Adducts of Myricetin

Cited by 17 publications

References 26 publications

Myricetin, the Main Flavonoid in Syzygium cumini Leaf, Is a Novel Inhibitor of Platelet Thiol Isomerases PDI and ERp5

Myricetin, the Main Flavonoid in Syzygium cumini Leaf, Is a Novel Inhibitor of Platelet Thiol Isomerases PDI and ERp5

Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway

Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro

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