Abstract
Platelet activation and accumulation at the site of vascular injury are central to thrombus formation resulted in thrombotic disorders. Medicinal herbs could be one of the most important pharmaceutical agents that ameliorate thrombotic disorders, such as unstable angina, myocardial infarction, stroke, and peripheral vascular diseases. Hwangryunhaedok-tang (HRT) is a traditional herbal medicine that displays multiple biological properties including anti-inflammatory abilities. However, its role in platelet activation has not been fully studied. Hence, we examined whether HRT has a potent inhibitory effect on platelet aggregation and thrombus formation. We demonstrated that HRT (30, 50, and 100 μg/ml) significantly impaired thrombin- and collagen-related peptide-induced platelet aggregation, granule secretion, thromboxane B2 generation, and intracellular Ca2+ mobilization. Biochemical studies revealed that HRT is involved in inhibiting the phosphorylation of phospholipase C and protein kinase B. The oral administration of HRT (30, 50, and 100 mg/kg once daily for 1 and/or 7 days) efficiently ameliorates ferric chloride induced arterial thrombus formation in vivo. Tail bleeding time was not significantly increased. The qualitative phytochemical constituents of the HRT extract were investigated using high-performance liquid chromatography. Our results demonstrated that HRT shows potential antiplatelet and antithrombotic effects without affecting hemostasis. Hence, HRT could be an effective therapeutic agent for the treatment of thrombotic diseases.
Highlights
Platelets play an important role in both thrombosis and hemostasis
In pathological condition, unwanted platelet activation leads to increased platelet aggregation and pathologic thrombosis, which is a primary factor in the development of thrombotic disorders, including unstable angina, myocardial infarction, ischemic stroke, and peripheral vascular diseases (Davies and Thomas, 1985; Genton et al, 1986; Trip et al, 1990)
Thromboxane B2 (TXB2) was dramatically elevated by both agonists, but HRT showed a potent inhibition of thrombin and Collagen-related peptide (CRP)-induced TXB2 formation in a concentration-dependent manner (Figures 2C,D). These results suggest that HRT plays an important role in stimulating platelet aggregation, Adenosine triphosphate (ATP) secretion, and TXB2 generation
Summary
Platelets play an important role in both thrombosis and hemostasis. Platelet adhesion and activation at the site of activated endothelial cells and/or subendothelial matrix proteins such as collagen and von Willebrand factor are the first steps in hemostasis (Nieswandt et al, 2002). In pathological condition, unwanted platelet activation leads to increased platelet aggregation and pathologic thrombosis, which is a primary factor in the development of thrombotic disorders, including unstable angina, myocardial infarction, ischemic stroke, and peripheral vascular diseases (Davies and Thomas, 1985; Genton et al, 1986; Trip et al, 1990). Understanding the mechanism underlying platelet activation and aggregation that precisely inhibits platelet functions is important as a promising approach for the treatment of thrombotic diseases
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