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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00923

Xinmailong modulates platelet function and inhibits thrombus formation via the platelet α II bβ3-mediated signaling pathway

 Huawei Wang1,  Zhaohui Meng1*,  Yujia Ye1,  Wen Wan1, Luqiao Wang1, Ruijie Li1,  Longjun Li1,  Lihong Yang1, Lai Yang1, Yajuan Gu1 and Ling Dong1
  • 1First Affiliated Hospital of Kunming Medical University, China

Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects.

Mathods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model.

Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen- and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagen-epinephrine-induced acute pulmonary thrombosis mouse model.

Conculsions and general significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.

Keywords: Xinmailong, Platelet, Thrombosis, α II bβ3, Traditinal medicine

Received: 24 Feb 2019; Accepted: 22 Jul 2019.

Copyright: © 2019 Wang, Meng, Ye, Wan, Wang, Li, Li, Yang, Yang, Gu and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Zhaohui Meng, First Affiliated Hospital of Kunming Medical University, Kunming, China, zhhmeng@aliyun.com