The hemostatic effect study of Cirsium setosum on regulating α1-ARs via mediating norepinephrine synthesis by enzyme catalysis

Biomed Pharmacother. 2017 Mar:87:698-704. doi: 10.1016/j.biopha.2017.01.022. Epub 2017 Jan 12.

Abstract

Background: Cirsium setosum (CS) is the aboveground part of Cephalanoplos segetum Kitam. Although it has been used as a hemostatic treatment for thousands of years and is still in use today, the mechanism of CS on regulating ARs is still not clear.

Purpose: In this study, we aimed to clarify the mechanism of CS on regulating ARs.

Methods: We developed a simple method based on UPLC/Q-TOF MS combined adrenergic receptor dual-luciferase reporter assay systems for the rapid determination of active constituents in CS. The mechanism of tyramine, the main active component for regulating ARs, was further investigated by an in vitro norepinephrine biotransformation test and in vivo vaso activity tests.

Results: Two phenethylamine ARs regulators (tyramine and N-methyltyramine) in CS were characterized, and it was found that tyramine could induce vasoconstriction via regulation of α1-ARs by mediating norepinephrine synthesis.

Conclusion: The hemostatic effect of CS is associated with tyramine and N-methyltyramine, via regulation of α1-ARs, and the mechanism of tyramine is related to mediating norepinephrine synthesis by enzyme catalysis.

Keywords: Adrenergic receptor; Cirsium setosum; Norepinephrine; Tyramine.

MeSH terms

  • Animals
  • Catalysis / drug effects*
  • Cell Line
  • Cirsium / chemistry*
  • HEK293 Cells
  • Hemostatics / pharmacology*
  • Humans
  • Male
  • Norepinephrine / metabolism*
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic / metabolism*
  • Tyramine / analogs & derivatives
  • Tyramine / pharmacology

Substances

  • Hemostatics
  • Plant Extracts
  • Receptors, Adrenergic
  • methyl-4-tyramine
  • Norepinephrine
  • Tyramine