Effect of Polyphenols From Campomanesia adamantium on Platelet Aggregation and Inhibition of Cyclooxygenases: Molecular Docking and in Vitro Analysis

Lescano, Caroline Honaiser; Lima, Fernando Freitas de; Mendes-Silvério, Camila B.; Justo, Alberto Fernando Oliveira; Baldivia, Débora da Silva; Vieira, Cristiano Pedrozo; Sanjinez-Argandoña, Eliana Janet; Cardoso, Cláudia Andréa Lima; Mónica, Fabíola Z.; Oliveira, Ivan Pires de

doi:10.3389/fphar.2018.00617

Cited by 41 publications

(21 citation statements)

References 65 publications

(82 reference statements)

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“…This is in agreement with previous reports showing that myricetin strongly inhibited collagen- (Dutta-Roy et al, 1999) and arachidonic acid-evoked platelet aggregation (Lescano et al, 2018). Interestingly this latter work reported that myricetin does not inhibit cyclooxygenase activity in platelets (Lescano et al, 2018). It has been described that gallic acid is able to inhibit platelet aggregation only at exceedingly high concentrations (Chang et al, 2012) which is corroborated by our data showing no effect below 300 mM.…”

Section: Discussionsupporting

confidence: 94%

“…Myricetin inhibited platelet aggregation and activation induced by agonists of the collagen and thrombin pathways, whereas gallic acid showed little to no effect even at 10× higher concentrations. This is in agreement with previous reports showing that myricetin strongly inhibited collagen- (Dutta-Roy et al, 1999) and arachidonic acid-evoked platelet aggregation (Lescano et al, 2018). Interestingly this latter work reported that myricetin does not inhibit cyclooxygenase activity in platelets (Lescano et al, 2018).…”

Section: Discussionsupporting

confidence: 94%

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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: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 94%

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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“…In this study, we investigated the maintenance effect of myricetin against human hepatocyte functional capacity and its involvement in the MAPK pathways. Myricetin showed antioxidative, cytoprotective, anti-carcinogenic, antimicrobial, and anti-platelet properties [12,15,[32][33][34], which are all beneficial for cell engraftment. We hope the results presented here will help to demonstrate that myricetin treatment has the potential to make a significant contribution to the development of cell transplantation therapies.…”

Section: Discussionmentioning

confidence: 99%

Natural Flavonol, Myricetin, Enhances the Function and Survival of Cryopreserved Hepatocytes In Vitro and In Vivo

Cui

Enosawa

Matsunari

et al. 2019

IJMS

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To improve the therapeutic potential of hepatocyte transplantation, the effects of the mitogen-activated protein kinase kinase 4 (MKK4) inhibitor, myricetin (3,3′,4′,5,5′,7-hexahydroxylflavone) were examined using porcine and human hepatocytes in vitro and in vivo. Hepatocytes were cultured, showing the typical morphology of hepatic parenchymal cell under 1–10 µmol/L of myricetin, keeping hepatocyte specific gene expression, and ammonia removal activity. After injecting the hepatocytes into neonatal Severe combined immunodeficiency (SCID) mouse livers, cell colony formation was found at 10–15 weeks after transplantation. The human albumin levels in the sera of engrafted mice were significantly higher in the recipients of myricetin-treated cells than non-treated cells, corresponding to the size of the colonies. In terms of therapeutic efficacy, the injection of myricetin-treated hepatocytes significantly prolonged the survival of ornithine transcarbamylase-deficient SCID mice from 32 days (non-transplant control) to 54 days. Biochemically, the phosphorylation of MKK4 was inhibited in the myricetin-treated hepatocytes. These findings suggest that myricetin has a potentially therapeutic benefit that regulates hepatocyte function and survival, thereby treating liver failure.

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“…Peel extract of Campomanesia adamantium (Cambess.) O. Berg showed antiaggregatory effect in platelet aggregation assay induced by arachidonic acid at 2.5 g L -1 concentration (8.2 mmol L -1 of quercetin equivalent) (43). This was attributed to quercetin and myricetin.…”

Section: Mechanisms Of Antiplatelet Action Of Individual Flavonoids Hmentioning

confidence: 90%

Antithrombotic activity of flavonoids and polyphenols rich plant species

et al. 2019

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Cardiovascular diseases represent one of the most notable health problems of the modern civilization. Stroke and heart attack often lead to lethal outcome; essential problem underneath being thrombus formation. Prophylactic approaches include acetylsalicylic acid and clopidogrel therapy on the level of primary hemostasis, i.e., primary clot formation. In the last five years, in the USA, health care expenses related to cardiovascular diseases have increased 50 %, to over 350 billion dollars. Thus, application of plant species and medicinal plants rich in polyphenols in prevention of thrombus formation are of interest. This is supported by the fact that the number of publications on antiaggregatory effect of polyphenols has doubled in the last decade. In this review we focus on antiaggregatory effect of most abundant polyphenols – flavonoids, the effect of plant extracts rich in polyphenols (propolis, species Salvia sp., Calamintha nepeta L., Lavandula angustifolia Mill., Melissa officinalis L, Mentha x piperita L., Ocimum basilicum L., Origanum vulgare L., Rosmarinus officinalis L.) on platelet aggregation, association of chemical composition and antioxidant properties with the observed biological effect, and possible clinical significance of the published results.

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Effect of Polyphenols From Campomanesia adamantium on Platelet Aggregation and Inhibition of Cyclooxygenases: Molecular Docking and in Vitro Analysis

Cited by 41 publications

References 65 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

Natural Flavonol, Myricetin, Enhances the Function and Survival of Cryopreserved Hepatocytes In Vitro and In Vivo

Antithrombotic activity of flavonoids and polyphenols rich plant species

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