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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.

Original publication

DOI

10.1248/bpb.b15-00511

Type

Journal article

Journal

Biol Pharm Bull

Publication Date

2016

Volume

39

Pages

181 - 191

Keywords

Animals, Apigenin, Blood Platelets, Calcium, Cell Adhesion, Cyclic AMP, Dose-Response Relationship, Drug, Erigeron, Fibrinogen, Isoenzymes, Male, Molecular Structure, Platelet Activation, Platelet Aggregation, Protein Kinase C beta, Protein Kinase C-alpha, Rats, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled