Affiliation:
1. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department
of Pharmacology of Chinese Materia Medica, School of Traditional Pharmacy, China Pharmaceutical University, 639 Longmian
Road, Nanjing 211198, PR China
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.
Funder
“Double First-Class” University Project
Fundamental Research Funds for the Central Universities
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Cited by
4 articles.
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