Flavonoids as a therapeutical option for the treatment of thrombotic complications associated with COVID‐19

Abstract

The SARS‐CoV‐2 outbreak has been one of the largest public health crises globally, while thrombotic complications have emerged as an important factor contributing to mortality. Therefore, compounds that regulate the processes involved in thrombosis could represent a dietary strategy to prevent thrombotic complications involved in COVID‐19. In August 2022, various databases were consulted using the keywords “flavonoids”, “antiplatelet”, “anticoagulant”, “fibrinolytic”, and “nitric oxide”. Studies conducted between 2019 and 2022 were chosen. Flavonoids, at concentrations mainly between 2 and 300 μM, are capable of regulating platelet aggregation, blood coagulation, fibrinolysis, and nitric oxide production due to their action on multiple receptors and enzymes. Most of the studies have been carried out through in vitro and in silico models, and limited studies have reported the in vivo and clinical effect of flavonoids. Currently, quercetin has been the only flavonoid evaluated clinically in patients with COVID‐19 for its effect on D‐dimer levels. Therefore, clinical studies in COVID‐19 patients analyzing the effect on platelet, coagulant, fibrinolytic, and nitric oxide parameters are required. In addition, further high‐quality studies that consider cytotoxic safety and bioavailability are required to firmly propose flavonoids as a treatment for the thrombotic complications implicated in COVID‐19.

Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huang–Qi–Gui–Zhi–Wu–Wu decoction against deep vein thrombosis

“…By constructing and analyzing databases and network diagrams of traditional Chinese medicine prescriptions, we identified quercetin, beta-sitosterol, and kaempferol as highly correlated with DVT. Previous studies demonstrated that quercetin and its derivatives possess anticoagulant, antiplatelet, and antifibrinolytic activities [ 37 , 38 ], effectively preventing pulmonary thromboembolism [ 39 ]. Furthermore, onion extracts rich in quercetin regulate MAPK under coagulation stimulation to prolong thrombosis time [ 40 ], consistent with our KEGG enrichment analysis results.…”

Exploring the potential mechanism and molecular targets of Taohong Siwu Decoction against deep vein thrombosis based on network pharmacology and analysis docking

“…Previous research has indicated that quercetin and its derivatives possess antifibrinolytic, anticoagulant, and antiplatelet properties. [ 35 , 36 ] Moreover, in mouse models, quercetin has been shown to inhibit thrombosis by inhibiting protein disulfide isomerase (PDI). [ 37 ] Both kaempferol and quercetin are flavonoids that regulate the interaction between fibrinogen and thrombin to prevent thrombosis while inhibiting prothrombin activity in vitro and in vivo.…”

Flavonoids as CYP3A4 Inhibitors In Vitro

“…They can inhibit the aggregation of platelets, the blood cells responsible for forming clots. This inhibition reduces the risk of blood clot formation, which can lead to stroke, heart attack, and other cardiovascular complications [ 98 ]. While more research is needed to fully elucidate the mechanisms underlying these benefits, accumulating evidence suggests that flavonoids play a protective role in various aspects of human health.…”