Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production

Sixuan Zhang; Xiang Gui; Yangyang Ding; Huan Tong; Wen Ju; Yue Li; Zhenyu Li; Lingyu Zeng; Kailin Xu; Jianlin Qiao

doi:10.3389/fphar.2021.717725

Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production

Front Pharmacol. 2021 Jul 22:12:717725. doi: 10.3389/fphar.2021.717725. eCollection 2021.

Authors

Sixuan Zhang^{1

2

3}, Xiang Gui^{1

2

3}, Yangyang Ding^{1

2

3}, Huan Tong^{1

2

3}, Wen Ju^{1

2

3}, Yue Li⁴, Zhenyu Li^{1

2

3}, Lingyu Zeng^{1

2

3

4}, Kailin Xu^{1

2

3}, Jianlin Qiao^{1

2

3}

Affiliations

¹ Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
² Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
³ Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China.
⁴ School of Medical Technology, Xuzhou Medical University, Xuzhou, China.

Abstract

Matrine is a naturally occurring alkaloid and possesses a wide range of pharmacological properties, such as anti-cancer, anti-oxidant, anti-inflammatory effects. However, whether it affects platelet function and thrombosis remains unclear. This study aims to evaluate the effect of matrine on platelet function and thrombus formation. Human platelets were treated with matrine (0-1 mg/ml) for 1 h at 37°C followed by measuring platelet aggregation, granule secretion, receptor expression by flow cytometry, spreading and clot retraction. In addition, matrine (10 mg/kg) was injected intraperitoneally into mice to measure tail bleeding time, arterial and venous thrombus formation. Matrine dose-dependently inhibited platelet aggregation and ATP release in response to either collagen-related peptide (Collagen-related peptide, 0.1 μg/ml) or thrombin (0.04 U/mL) stimulation without altering the expression of P-selectin, glycoprotein Ibα, GPVI, or αIIbβ3. In addition, matrine-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction along with reduced phosphorylation of c-Src. Moreover, matrine administration significantly impaired the in vivo hemostatic function of platelets, arterial and venous thrombus formation. Furthermore, in platelets stimulated with CRP or thrombin, matrine significantly reduced Reactive oxygen species generation, inhibited the phosphorylation level of ERK1/2 (Thr202/Tyr204), p38 (Thr180/Tyr182) and AKT (Thr308/Ser473) as well as increased VASP phosphorylation (Ser239) and intracellular cGMP level. In conclusion, matrine inhibits platelet function, arterial and venous thrombosis, possibly involving inhibition of ROS generation, suggesting that matrine might be used as an antiplatelet agent for treating thrombotic or cardiovascular diseases.

Keywords: ROS; hemostasis; matrine; platelet; thrombosis.