Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotides

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 activatio...

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Main Authors: Ga Hee Lee, Jin Pyo Lee, Na Yoon Heo, Chang-Dae Lee, Gyeongchan Kim, Akram Abdul Wahab, Man Hee Rhee, Sanghyun Lee, Dong-Ha Lee
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-09452-7
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author Ga Hee Lee
Jin Pyo Lee
Na Yoon Heo
Chang-Dae Lee
Gyeongchan Kim
Akram Abdul Wahab
Man Hee Rhee
Sanghyun Lee
Dong-Ha Lee
author_facet Ga Hee Lee
Jin Pyo Lee
Na Yoon Heo
Chang-Dae Lee
Gyeongchan Kim
Akram Abdul Wahab
Man Hee Rhee
Sanghyun Lee
Dong-Ha Lee
author_sort Ga Hee Lee
collection DOAJ
description 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.
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spelling doaj-art-21ea9b59318d45fa89f8e25fb67b1e732025-08-20T03:04:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-09452-7Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotidesGa Hee Lee0Jin Pyo Lee1Na Yoon Heo2Chang-Dae Lee3Gyeongchan Kim4Akram Abdul Wahab5Man Hee Rhee6Sanghyun Lee7Dong-Ha Lee8Department of Biomedical Laboratory Science, Namseoul UniversityDepartment of Biomedical Laboratory Science, Namseoul UniversityDepartment of Biomedical Laboratory Science, Namseoul UniversityDepartment of Plant Science and Technology, Chung-Ang UniversityDepartment of Health Administration and Management, Soonchunhyang University Graduate SchoolDepartment of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National UniversityDepartment of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National UniversityDepartment of Plant Science and Technology, Chung-Ang UniversityDepartment of Biomedical Laboratory Science, Namseoul UniversityAbstract 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.https://doi.org/10.1038/s41598-025-09452-7
spellingShingle Ga Hee Lee
Jin Pyo Lee
Na Yoon Heo
Chang-Dae Lee
Gyeongchan Kim
Akram Abdul Wahab
Man Hee Rhee
Sanghyun Lee
Dong-Ha Lee
Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotides
Scientific Reports
title Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotides
title_full Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotides
title_fullStr Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotides
title_full_unstemmed Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotides
title_short Dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up-regulating cyclic nucleotides
title_sort dioscin from smilax china rhizomes inhibits platelet activation and thrombus formation via up regulating cyclic nucleotides
url https://doi.org/10.1038/s41598-025-09452-7
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