Celastrol inhibits platelet function and thrombus formation

  • Biochem Biophys Res Commun. 2023 Dec 10:693:149366. doi: 10.1016/j.bbrc.2023.149366.
Xiaoqian Li  1 ,  Jie Zhang  1 ,  Yingying Li  1 ,  Yue Dai  1 ,  Hui Zhu  1 ,  Huimin Jiang  1 ,  Yiran Han  2 ,  Xiang Chu  1 ,  Yueyue Sun  1 ,  Wen Ju  1 ,  Zhenyu Li  1 ,  Lingyu Zeng  1 ,  Kailin Xu  1 ,  Jianlin Qiao  3
Affiliations
  • 1. Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
  • 2. The First Clinical School of Medicine, Xuzhou Medical University, Xuzhou, China.
  • 3. Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. Electronic address: [email protected].
PMID: 38091842 DOI: 10.1016/j.bbrc.2023.149366
Abstract

Introduction: Celastrol is an active pentacyclic triterpenoid extracted from Tripterygium wilfordii and has anti-inflammatory and anti-tumor properties. Whether Celastrol modulates platelet function remains unknown. Our study investigated its role in platelet function and thrombosis.

Methods: Human platelets were isolated and incubated with Celastrol (0, 1, 3 and 5 μM) at 37 °C for 1 h to measure platelet aggregation, granules release, spreading, thrombin-induced clot retraction and intracellular calcium mobilization. Additionally, Celastrol (2 mg/kg) was intraperitoneally administrated into mice to evaluate hemostasis and thrombosis in vivo.

Results: Celastrol treatment significantly decreased platelet aggregation and secretion of dense or alpha granules induced by collagen-related peptide (CRP) or Thrombin in a dose-dependent manner. Additionally, Celastrol-treated platelets showed a dramatically reduced spreading activity and decreased clot retraction. Moreover, Celastrol administration prolonged tail bleeding time and inhibited formation of arterial/venous thrombosis. Furthermore, Celastrol significantly reduced calcium mobilization.

Conclusion: Celastrol inhibits platelet function and venous/arterial thrombosis, implying that it might be utilized for treating thrombotic diseases.

Keywords
Calcium mobilization; Celastrol; Hemostasis; Platelets; Thrombosis.
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