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Delineation of Platelet Activation Pathway of Scutellarein Revealed Its Intracellular Target as Protein Kinase C
- Source :
- Biologicalpharmaceutical bulletin. 39(2)
- Publication Year :
- 2015
-
Abstract
- Erigeron breviscapus has been widely used in traditional Chinese medicine (TCM) and its total flavonoid component is commonly used to treat ischemic stroke, coronary heart disease, diabetes and hypertension. Scutellarin is the major ingredient of E. breviscapus and scutellarein is one of the main bioactive metabolites of scutellarin in vivo, but the latter's pharmacological activities have not been fully characterized. Provided evidence that could inhibit platelet aggregation, the effect of scutellarein on rat washed platelets and its underlying mechanisms were evaluated in our research. Scutellarein inhibited platelet adhesion and aggregation induced by multiple G protein coupled receptor agonists such as thrombin, U46619 and ADP, in a concentration-dependent manner. Furthermore, the mild effect of scutellarein on intracellular Ca(2+) mobilization and cyclic AMP (cAMP) level was observed. On the other hand, the role of scutellarein as potential protein kinase C (PKC) inhibitor was confirmed by PKC activity analysis and molecular docking. The phorbol myristate acetate-induced platelets aggregation assay with or without ADP implied that the scutellarein takes PKC(s) as its primary target(s), and acts on it in a reversible way. Finally, scutellarein as a promising agent exhibited a high inhibition effect on ADP-induced platelet aggregation among its analogues. This study clarifies the PKC-related signaling pathway involved in antiplatelet action of scutellarein, and may be beneficial for the treatment of cardiovascular diseases.
- Subjects :
- 0301 basic medicine
Blood Platelets
Male
Protein Kinase C-alpha
Platelet Aggregation
Pharmaceutical Science
Protein Kinase C beta
Pharmacology
Receptors, G-Protein-Coupled
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Thrombin
medicine
Cell Adhesion
Cyclic AMP
Animals
Platelet activation
Apigenin
Protein kinase C
Scutellarin
Dose-Response Relationship, Drug
Molecular Structure
Scutellarein
Fibrinogen
General Medicine
Platelet Activation
Rats
Erigeron
Isoenzymes
030104 developmental biology
chemistry
Biochemistry
Phorbol
Calcium
Signal transduction
medicine.drug
Subjects
Details
- ISSN :
- 13475215
- Volume :
- 39
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biologicalpharmaceutical bulletin
- Accession number :
- edsair.doi.dedup.....b4c11f48698910d1b5799e466ea987d0