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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Ruscogenin Alleviates Deep Venous Thrombosis and Pulmonary Embolism Induced by Inferior Vena Cava Stenosis Inhibiting MEK/ERK/Egr-1/TF Signaling Pathway in Mice

Author(s): Yujie Dai, Qianliu Zhou, Yuankai Liu, Xiaojun Chen, Fang Li, Boyang Yu, Yuanyuan Zhang* and Junping Kou*

Volume 28, Issue 24, 2022

Published on: 15 July, 2022

Page: [2001 - 2009] Pages: 9

DOI: 10.2174/1381612828666220526120515

Price: $65

Abstract

Background: Ruscogenin (RUS) has anti-inflammatory and antithrombotic effects, while its potential effects on deep venous thrombosis (DVT) and pulmonary embolism (PE) remain unclear.

Objective: We aimed to elucidate the effects of RUS on DVT and PE induced by the inferior vena cava stenosis (IVCS) model and investigate the underlying mechanism.

Methods: Male C57/BL6 mice were used to explore whether IVCS model could be complicated with deep venous thrombosis and pulmonary embolism. Then, effects of RUS on DVT and PE related inflammatory factors and coagulation were examined using H&E staining, ELISA, and real-time PCR. Western blot analysis was used to examine the effects of RUS on MEK/ERK/Egr-1/TF signaling pathway in PE.

Results: IVCS model induced DVT and complied with PE 48 h after surgery. Administration of RUS (0.01, 0.1, 1 mg/kg) inhibited DVT, decreased biomarker D-Dimer, cardiac troponin I, N-Terminal probrain natriuretic peptide in plasma to ameliorate PE induced by IVCS model. Meanwhile, RUS reduced tissue factor and fibrinogen content of lung tissue, inhibited P-selectin and C-reactive protein activity in plasma, and suppressed the expressions of interleukin-6 and interleukin-1β in mice. Furthermore, RUS suppressed the phosphorylation of ERK1/2 and MEK1/2, decreasing the expressions of Egr-1 and TF in the lung.

Conclusion: IVCS model contributed to the development of DVT and PE in mice and was associated with increased inflammation. RUS showed therapeutic effects by inhibiting inflammation as well as suppressing the activation of MEK/ERK/Egr-1/TF signaling pathway.

Keywords: Inferior vena cava stenosis, deep venous thrombosis, pulmonary embolism, ruscogenin, MEK/ERK/Egr-1/TF, anticoagulant.

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