Magnolol, a novel antagonist of thrombin and par-1, inhibits thrombin-induced connective tissue growth factor (Ctgf) expression in vascular smooth muscle cells and ameliorate pathogenesis of restenosis in rats

Wen Chin Ko, Chia Ti Tsai, Kai Cheng Hsu, Yu Che Cheng, Tony Eight Lin, Yi Ling Chen, Chuang Ye Hong, Wan Jung Lu, Chun Ming Shih, Ting Lin Yen

Research output: Contribution to journalArticlepeer-review

Abstract

Restenosis and destructive vascular remodeling are the main reasons for treatment failure in patients undergoing percutaneous coronary intervention (PCI). In this study, we explored the efficacy of magnolol (a traditional Chinese medicine) in the treatment of restenosis. The results of this study showed that the activities of thrombin and PAR-1 (protease-activated receptor 1) were significantly decreased by the treatment of magnolol. Based on protein docking analysis, magnolol exhibits its potential to bind to the PAR-1 active site. In addition, thrombin-induced connective tissue growth factor (CTGF) expression and the upstream of CTGF such as JNK-1 (but not JNK-2), c-Jun, and AP-1 were distinctly inhibited by magnolol (50 µM) in vascular smooth muscle cells (VSMC). For the functional assay, magnolol (50 µM) significantly inhibited the migration of VSMC, and rats treated with magnolol (13 mg/kg/day) after balloon angioplasty has observed a significant reduction in the formation of common arterial neointima. In conclusion, we identified a novel mechanism by which magnolol acts as the thrombin activity inhibitor and may be the PAR-1 antagonist. In accordance with these functions, magnolol could decrease thrombin-induced CTGF expression in VSMCs via PAR-1/JNK-1/AP-1 signaling.

Original languageEnglish
Article number8729
Pages (from-to)1-16
Number of pages16
JournalApplied Sciences (Switzerland)
Volume10
Issue number23
DOIs
Publication statusPublished - Dec 1 2020

Keywords

  • CTGF
  • Magnolol
  • PAR-1
  • Restenosis
  • Thrombin inhibitor

ASJC Scopus subject areas

  • Materials Science(all)
  • Instrumentation
  • Engineering(all)
  • Process Chemistry and Technology
  • Computer Science Applications
  • Fluid Flow and Transfer Processes

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