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Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic
Ga Hee Lee1, Jin Pyo Lee1, Na Yoon Heo1
1Department of Biomedical Laboratory Science, Namseoul University, Cheonan, 31020, Republic of Korea.
Abstract:
Cardiovascular disease, the leading cause of mortality in the United States, is caused by abnormal platelet accumulation and coagulation. Dioscin has been reported to suppress the growth of tumor-associated cells and trigger apoptosis. However, its mechanism in inhibiting platelet activation has not been confirmed. This study investigates whether dioscin from Smilax china rhizomes exerts antithrombotic effects by regulating the activation of human platelets and explains its mechanism of action. Dioscin increased the production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). This increase induced the phosphorylation of inositol 1,4,5-triphosphate receptor (IP3R), which inhibited the dense Ca2+ release channels, thereby reducing Ca2+ mobilization. Furthermore, it promoted the phosphorylation of vasodilator-stimulated phosphoprotein (VASP), which suppressed integrin αIIbβ3 and fibrinogen binding, thus inhibiting platelet activation. Dioscin regulated phosphorylation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK) and cytosolic phospholipase A2 (cPLA2), which are proteins associated with platelet granule release. Finally, ingestion of S. china rhizomes containing dioscin significantly inhibited thrombus formation in the FeCl3-induced thrombosis model. Therefore, dioscin from S. china rhizomes exhibited antiplatelet effects that could delay or halt thrombus formation by regulating the phosphorylation of various signaling molecules and related proteins, thus suggesting dioscin's potential value for development as an antithrombotic agent.
Insights
Dioscin, found in Smilax china rhizomes, inhibits platelet activation and thrombus formation by regulating key signaling pathways. This natural compound shows potential as a novel antithrombotic agent for cardiovascular disease prevention.
Area of Science:
- Pharmacology
- Biochemistry
- Cardiovascular Research
Background:
- Cardiovascular disease is a leading cause of mortality, driven by abnormal platelet aggregation and coagulation.
- Dioscin, a compound from Smilax china rhizomes, is known for anti-tumor properties, but its antiplatelet mechanism is unconfirmed.
- Understanding dioscin's role in platelet function is crucial for developing new antithrombotic therapies.
Purpose of the Study:
- To investigate the antithrombotic effects of dioscin on human platelets.
- To elucidate the underlying molecular mechanisms by which dioscin inhibits platelet activation.
- To assess the in vivo efficacy of dioscin in preventing thrombus formation.
Main Methods:
- Assessed dioscin's impact on cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in platelets.
- Investigated dioscin's effects on the phosphorylation of inositol 1,4,5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP).
- Analyzed dioscin's regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), and cytosolic phospholipase A2 (cPLA2) signaling pathways.
- Evaluated dioscin's antithrombotic activity in a FeCl3-induced thrombosis model in vivo.
Main Results:
- Dioscin significantly increased cAMP and cGMP production, leading to IP3R and VASP phosphorylation.
- Inhibition of Ca2+ mobilization and suppression of integrin αIIbβ3 and fibrinogen binding were observed.
- Dioscin modulated the phosphorylation of PI3K/Akt, MAPK, and cPLA2, impacting platelet granule release.
- Administration of S. china rhizomes containing dioscin markedly reduced thrombus formation in vivo.
Conclusions:
- Dioscin exhibits significant antiplatelet activity by modulating intracellular signaling pathways and protein phosphorylation.
- The compound effectively inhibits platelet activation and thrombus formation, suggesting its therapeutic potential.
- Dioscin from S. china rhizomes represents a promising candidate for the development of novel antithrombotic agents.
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