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COVID-19 and Panax ginseng: Targeting platelet aggregation, thrombosis and the coagulation pathway.

ABSTRACT: Coronavirus disease 2019 (COVID-19) not only targets the respiratory system but also triggers a cytokine storm and a series of complications, such as gastrointestinal problems, acute kidney injury, and myocardial ischemia. The use of natural products has been utilized to ease the symptoms of COVID-19, and in some cases, to strengthen the immune system against COVID-19. Natural products are readily available and have been regularly consumed for various health benefits. COVID-19 has been reported to be associated with the risk of thromboembolism and deep vein thrombosis. These thrombotic complications often affects mortality and morbidity. Panax ginseng, which has been widely consumed for its various health benefits has also been reported for its therapeutic effects against cardiovascular disease, thrombosis and platelet aggregation. In this review, we propose that P. ginseng can be consumed as a supplementation against the various associated complications of COVID-19, especially against thrombosis. We utilized the network pharmacology approach to validate the potential therapeutic properties of P. ginseng against COVID-19 mediated thrombosis, the coagulation pathway and platelet aggregation. Additionally, we aimed to investigate the roles of P. ginseng against COVID-19 with the involvement of platelet-leukocyte aggregates in relation to immunity-related responses in COVID-19.

SUBMITTER: Lee YY

PROVIDER: S-EPMC8767971 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCritically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.MethodsUsing platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.ResultsWe demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count. Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients. Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation. SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates. Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.ConclusionsOur findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2. SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.

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COVID-19 and Panax ginseng: Targeting platelet aggregation, thrombosis and the coagulation pathway.

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