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

Abstract

Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different parts of its fruits are used in popular medicine to treat gastrointestinal disorders, rheumatism, urinary tract infections and inflammations. Despite its widespread use by the local population, the mechanisms involving platelet aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown. This study evaluated the chemical composition, antioxidant activities and potential benefits of the C. adamantium peel extract (CAPE) and its components in the platelet aggregation induced by arachidonic acid in platelet-rich plasma. Aspects of the pharmacological mechanism were investigated as follows: platelet viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP, thromboxane B2 levels, and the inhibitory effects on COX-1 and COX-2 were studied in vitro and using molecular docking in the catalytic domain of these proteins. The major CAPE constituents standing out from the chemical analysis are the flavonoids, namely those of the flavones and chalcones class. The results showed that CAPE, quercetin and myricetin significantly decreased arachidonic acid-induced platelet aggregation; the assays showed that CAPE and quercetin decreased the mobilization of calcium and thromboxane B2 levels in platelets and increased cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2, highlighting that quercetin could potentially prevent the access of arachidonic acid more to the catalytic site of COX-1 than COX-2. These results highlight CAPE’s potential as a promising therapeutic candidate for the prevention and treatment of diseases associated with platelet aggregation.

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

“…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.…”

“…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).…”

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

“…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.…”

Antithrombotic activity of flavonoids and polyphenols rich plant species

“…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.…”