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Antiplatelet Activity of Tussilagone via Inhibition of the GPVI Downstream Signaling Pathway in Platelets
- Source :
- Frontiers in Medicine, Vol 7 (2020), Frontiers in Medicine
- Publication Year :
- 2020
- Publisher :
- Frontiers Media S.A., 2020.
-
Abstract
- Tussilagone is a sesquiterpenoid extracted from Tussilago farfara and is used as an oriental medicine for asthma and bronchitis. Although previous studies have shown that tussilagone has an inhibitory effect on platelet aggregation, no studies have been performed to investigate its precise effect on platelets, and the underlying mechanism remains unclear. In the present study, we showed that tussilagone inhibited platelet aggregation induced by collagen, thrombin and ADP, as well as platelet release induced by collagen and thrombin, in mice. Tussilagone decreased P-selectin expression and αIIbβ3 activation (JON/A binding) in activated platelets, which indicated that tussilagone inhibited platelet activation. Moreover, tussilagone suppressed platelet spreading on fibrinogen and clot retraction. The levels of phosphorylated Syk, PLCγ2, Akt, GSK3β, and MAPK (ERK1/2 and P38) and molecules associated with GPVI downstream signaling were downregulated in the presence of tussilagone. In addition, tussilagone prolonged the occlusion time in a mouse model of FeCl3-induced carotid artery thrombosis and had no effect on mouse tail bleeding time. These results indicate that tussilagone inhibits platelet function in vitro and in vivo and that the underlying mechanism involves the Syk/PLCγ2-PKC/MAPK and PI3K-Akt-GSK3β signaling pathways downstream of GPVI. This research suggests that tussilagone is a potential candidate antiplatelet drug for the prevention of thrombosis.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Antiplatelet drug
medicine.medical_treatment
Syk
Clot retraction
030204 cardiovascular system & hematology
Pharmacology
antiplatelet
glycoprotein VI pathway
03 medical and health sciences
0302 clinical medicine
Thrombin
medicine
Platelet
Platelet activation
tussilagone
thrombosis
Original Research
lcsh:R5-920
Chemistry
sesquiterpenoid
General Medicine
030104 developmental biology
Medicine
GPVI
lcsh:Medicine (General)
medicine.drug
Subjects
Details
- Language :
- English
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Frontiers in Medicine
- Accession number :
- edsair.doi.dedup.....2053639f06e253990cf7e26f5b28ae58