Pharmacological actions of neferine in the modulation of human platelet function
| Autor: | Zhang-Yin Ming, Wei Song, Ya-Jun Zhou, Ao-Di He, Ru-Ping Yang, Zhao Yin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Blood Platelets Male Platelet Aggregation MAP Kinase Signaling System Integrin Drug Evaluation Preclinical Pharmacology Fibrinogen Benzylisoquinolines p38 Mitogen-Activated Protein Kinases 03 medical and health sciences Phosphatidylinositol 3-Kinases Young Adult 0302 clinical medicine Thrombin medicine Cell Adhesion Humans Platelet Phosphorylation Protein kinase B PI3K/AKT/mTOR pathway Glycogen Synthase Kinase 3 beta biology Chemistry Fibrinogen binding Thrombosis Healthy Volunteers 030104 developmental biology biology.protein Female Platelet alpha-granule Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Platelet Aggregation Inhibitors medicine.drug Drugs Chinese Herbal |
| Zdroj: | European journal of pharmacology. 862 |
| ISSN: | 1879-0712 |
| Popis: | Neferine has long been recognized as a medicinal herbal ingredient with various physiological and pharmacological activities. Although previous studies have reported its antithrombotic effect, the underlying mechanisms have not been thoroughly investigated. Since platelets play a key role in thrombosis, we investigated the effects of neferine on human platelet function and the potential mechanisms. Platelet aggregation, adhesion and spreading were performed to investigate the effect of neferine on inhibition of platelet function. Flow cytometry was used to determine platelet alpha granule secretion and integrin IIb/IIIa activation, as detected by CD62P (P-selectin) expression, PAC-1 and fibrinogen binding. Western blotting was utilized to investigate the effect of neferine on intracellular signaling of activated platelet. We found that neferine significantly suppressed platelet aggregation and remarkably promoted the dissociation of platelet aggregates induced by collagen, thrombin, U46619, ADP and adrenaline in a dose-dependent manner. Flow cytometry analysis showed that neferine inhibited thrombin-induced platelet P-selectin expression, PAC-1 and fibrinogen binding. In addition, neferine reduced the adhesion of human platelets on coated collagen under both static and shearing condition at an arterial shear rate of 40 dyne/cm2. Neferine also inhibited the spreading of human platelets on immobilized fibrinogen. Western blot analysis showed that neferine inhibited PI3K activation, and decreased the levels of phosphorylation of Akt, GSK3β and p38 MAPK in platelets. In summary, neferine has the potential to be an antiplatelet and antithrombotic agent by inhibiting the PI3K-Akt-GSK3β/p38 MAPK signaling pathway. |
| Databáze: | OpenAIRE |
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