Abstract
Background Platelets play major role in maintaining hemostasis while hyperactivation of platelets may lead to arterial thrombosis. Natural products and ethnomedicine have been shown to reduce the risk of cardiovascular diseases (CVDs). Astilbe chinensis is a perennial herb found in China, Korea, Russia, and Japan, which is also known for its medicinal effects, and has been used in Korean traditional medicine to treat inflammation, cancer, chronic bronchitis, and headache. We hypothesized that given herbal plant exhibits pharmacological activities against CVDs, and we specifically explored their effects on platelet function. Methodology Platelet aggregation was evaluated using standard light-transmission aggregometry. Intracellular calcium mobilization was assessed using Fura-2/AM, and granule secretion (ATP release) was measured in a luminometer. Fibrinogen binding to integrin αIIbβ3 was assessed using flow cytometry. Phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules and activation of the phosphoinositide 3-kinase (PI3K)/Akt were assessed using western blots, and further, glycoprotein VI (GPVI) signaling components were studied using immunoprecipitation. Key Results A. chinensis extracts potently and significantly inhibited platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αIIbβ3. Moreover, it significantly inhibited MAPK phosphorylation and expression of GPVI downstream signaling molecules. Conclusion A. chinensis extract inhibited platelet aggregation and granule secretion and attenuated GPVI downstream signaling, indicating the potential therapeutic effects of this plant extract on the cardiovascular system and platelet function. We suggest that given plant extract may be a potent candidate to treat platelet-related CVDs and to be used as antiplatelet agent.
Highlights
Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in developed countries [1]
A significant and concentration-dependent inhibition of platelet aggregation was observed in platelets pretreated with A. chinensis extract compared with that of vehicle control (Figure 1(b))
We assessed activation of this pathway in collagen-stimulated platelets pretreated with A. chinensis extract and found that our extract had significant inhibitory potential against the activation of this pathway (Figure 4(b)). These results show that A. chinensis extract potentially inhibits platelet aggregation by inhibiting phosphorylation of mitogen-activated protein kinase (MAPK) and MAPKK signaling proteins and phosphoinositide 3-kinase (PI3K)/Akt pathway activation
Summary
Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in developed countries [1]. Intravascular thrombosis is a factor that causes various CVDs. Pharmacological suppression of platelet function has shown great success in reducing thrombotic events, and a number of clinically approved antiplatelet drugs are available to treat cardiovascular ailments. Pharmacological suppression of platelet function has shown great success in reducing thrombotic events, and a number of clinically approved antiplatelet drugs are available to treat cardiovascular ailments These drugs can have serious complications (such as gastric bleeding) and are ineffective in some patients [4, 5], necessitating the need to develop effective and safer approaches to treat and prevent CVDs. One approach may include the use of natural products, like plant extracts, as antithrombotics and anticoagulants [6]. A. chinensis extracts potently and significantly inhibited platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αIIbβ. A. chinensis extracts potently and significantly inhibited platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αIIbβ3 It significantly inhibited MAPK phosphorylation and expression of GPVI downstream signaling molecules. We suggest that given plant extract may be a potent candidate to treat platelet-related CVDs and to be used as antiplatelet agent
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