ReferenceID 1727
Danshensu prevents thrombosis by inhibiting platelet activation via SIRT1/ROS/mtDNA pathways without increasing bleeding risk
Phytomedicine
Background: Coronary thrombosis and its correlated disorders are main healthcare problems globally. The therapeutic effects of current treatments involving antiplatelet drugs are not fully satisfactory. Danshensu (DSS) i
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- Reference Id
- 1727
- Evidence Id
- 18317
- Core Evidence Id
- 18317
- Source Reference Id
- 3437
- Herb2 Reference Id
- HBREF004234
- Subject Paper Key
- HBIN022650_35777120
- Pubmed Id
- 35777120
- Doi
- 10.1016/j.phymed.2022.154271
- Paper Title
- Danshensu prevents thrombosis by inhibiting platelet activation via SIRT1/ROS/mtDNA pathways without increasing bleeding risk
- Paper Abstract
- Background: Coronary thrombosis and its correlated disorders are main healthcare problems globally. The therapeutic effects of current treatments involving antiplatelet drugs are not fully satisfactory. Danshensu (DSS) is an important monomer obtained from Salvia miltiorrhiza roots that have been widely employed for vascular diseases in medicinal practices. Nonetheless, the underlying mechanisms of DSS are not fully unraveled. Purpose: The objective of this study was to penetrate the antithrombotic and antiplatelet mechanisms of DSS. Methods: Network pharmacology assay was used to forecast the cellular mechanisms of DSS for treating thrombosis. The work focused the impacts of DSS on platelet activation by analyzing aggregation and adhesion in vitro. Flow cytometry, western blotting, CM-H2DCFDA staining and mitochondrial function assays were performed to reveal the molecular mechanisms. The model of common carotid artery thrombus induced by ferric chloride was established. The wet weight of thrombus was measured, and the thrombosis was observed by hematoxylin and eosin (H&E) staining, in order to support the inhibitory effect of DSS on thrombosis. Results: Data mining found the antithrombotic effect of DSS is related to platelet activation and the core target is silent information regulator 1 (SIRT1). We confirmed that DSS dose-dependently inhibited platelet activation in vitro. DSS was further demonstrated to induce the expression of SIRT1 and decreased reactive oxygen species (ROS) burden and thereby prevented mitochondrial dysfunction. Mitochondrial function tests further indicated that DSS prevented mitochondrial DNA (mtDNA) release, which induced activation of platelet in a dendritic cell specific intercellular-adhesion-molecule-3 grabbing non-integrin (DC-SIGN)-dependent manner. In carotid artery injury model induced by ferric chloride, DSS inhibited the development of carotid arterial thrombosis. More encouragingly, in tail bleeding time assay, DSS did not augment bleeding risk. Conclusion: These findings indicated that DSS effectively inhibited platelet activation by depressing the collection of ROS and the release of platelet mtDNA without arousing hemorrhage risk. DSS might represent a promising candidate drug for thrombosis and cardiovascular disease therapeutics.
- Journal
- Phytomedicine
- Publish Year
- 2022
- Experiment Subject
- Experiment Type
- Animal Experiment
- Phenotype Related
- Mitochondrial Dysfunction; Hemorrhage; Coronary Thrombosis; Cardiovascular Disease; Carotid Artery Injury; Carotid Arterial Thrombosis; Carotid Artery Thrombus; Vascular Diseases; Thrombosis
- Paper Title Cn
- Paper Title En
- Danshensu prevents thrombosis by inhibiting platelet activation via SIRT1/ROS/mtDNA pathways without increasing bleeding risk
- Bilingual Status
- semi_complete