Cimicifugamide from Cimicifuga rhizomes functions as a nonselective β-AR agonist for cardiac and sudorific effects

Biomed Pharmacother. 2017 Jun:90:122-130. doi: 10.1016/j.biopha.2017.03.058. Epub 2017 Mar 26.

Abstract

Cimicifuga rhizomes (CR) are used in the treatment of respiratory and cardiovascular diseases in traditional Chinese medicine, but their key effective components and mechanism of action have not yet been reported. In this study, the cardiac, antipyretic and sudorific effects of CR were evaluated using the toad heart failure in vitro model and mice fever and sweating in vivo models. Moreover, the UPLC/Q-TOF-MS-integrated β2-AR luciferase reporter gene assay system was used to screen the bioactive ingredients from CR extract, and the activity of this ingredient were verified using the above-mentioned in vitro and vivo models. Our results showed that CR had anti-heart failure, antipyretic and sweating effects, which could be antagonized by propranolol. On the other hand, cimicifugamide was screened as β2-AR agonist from CR and cimicifugamide could activate β1, 2-ARs more significantly than β3-AR in β-ARs selectivity assessment. The results not only revealed the key effective components and mechanism of CR in traditional use but also supplied a characteristic complementary ingredient for quality control of CR.

Keywords: Antipyretic; Cardiac; Cimicifuga rhizomes; Cimicifugamide; Sudorific; β-AR agonist.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology*
  • Animals
  • CHO Cells
  • Cell Line
  • Cimicifuga / chemistry*
  • Cricetulus
  • Disease Models, Animal
  • Glycosides / pharmacology*
  • HEK293 Cells
  • Heart / drug effects*
  • Heart Failure / drug therapy
  • Heart Failure / metabolism
  • Humans
  • Isoproterenol / pharmacology
  • Male
  • Mice
  • Plant Extracts / pharmacology
  • Rhizome / chemistry*

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Glycosides
  • Plant Extracts
  • cimicifugamide
  • Isoproterenol