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

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.

• Authors: Yujie Dai, Qianliu Zhou, Yuankai Liu, Xiaojun Chen, Fang Li, Boyang Yu, Yuanyuan Zhang, Junping Kou
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 28 Issue 24 Pg. 2001-2009 ( 2022) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 35619253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Spirostans
• Thromboplastin
• ruscogenin
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Constriction, Pathologic (complications)
• Inflammation (complications)
• MAP Kinase Signaling System
• Male
• Mice
• Mitogen-Activated Protein Kinase Kinases (metabolism, pharmacology, therapeutic use)
• Pulmonary Embolism (drug therapy)
• Signal Transduction
• Spirostans
• Thromboplastin (metabolism, pharmacology, therapeutic use)
• Vena Cava, Inferior (metabolism)
• Venous Thrombosis (drug therapy)