2. Academic Validation
  3. Danshensu prevents thrombosis by inhibiting platelet activation via SIRT1/ROS/mtDNA pathways without increasing bleeding risk

Danshensu prevents thrombosis by inhibiting platelet activation via SIRT1/ROS/mtDNA pathways without increasing bleeding risk

  • Phytomedicine. 2022 Sep:104:154271. doi: 10.1016/j.phymed.2022.154271.
Yuejin Xue 1,  Liyuan Zhang 2,  Lusha Zhang 2,  Wei Sun 2,  Zhirui Fang 2,  Yuze Leng 2,  Mengyao Li 2,  Xiuyun Ren 2,  Rui Zhang 2,  Yingxue Zhang 3,  Lu Chen 4,  Hong Wang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China.
  • 2 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China.
  • 3 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China.
  • 4 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, 301617 Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, 301617 Tianjin, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China; Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, 301617 Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, 301617 Tianjin, China; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China. Electronic address: [email protected].
PMID: 35777120 DOI: 10.1016/j.phymed.2022.154271
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.

Keywords

Danshensu; Mitochondrial DNA; Platelet activation; ROS; SIRT1; Thrombosis.

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