Prostate cell membrane chromatography-liquid chromatography-mass spectrometry for screening of active constituents from Uncaria rhynchophylla

J Chromatogr Sci. Nov-Dec 2013;51(10):905-9. doi: 10.1093/chromsci/bms188. Epub 2012 Nov 28.

Abstract

Uncaria rhynchophylla is a traditional Chinese medicinal herb used to treat hypertension and convulsive disorders such as epilepsy. Rat prostate cell membrane chromatography combined with liquid chromatography-mass spectrometry (LC-MS) was used to identify active constituents from U. rhynchophylla extracts. Four compounds (corynoxeine, isorhynchophylline, isocorynoxeine and rhynchophylline) were discovered. Competitive binding assay results indicated that the four compounds were in direct competition at a single common binding site and interacted with α1A adrenergic receptors (α1A-AR) in a manner similar to tamsulosin. Affinity constant values of the four compounds binding with α1A-AR were also measured using rat prostate cell membrane chromatography (CMC). Finally, their pharmacodynamic effects were tested on rat caudal arteries. This CMC combined LC-MS system offers a means of drug discovery by screening natural medicinal herbs for new pharmacologically active molecules targeting specific receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / analysis
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacokinetics
  • Alkaloids / pharmacology
  • Animals
  • Binding, Competitive
  • Cell Membrane / metabolism*
  • Chromatography, Liquid* / instrumentation
  • Chromatography, Liquid* / methods
  • HEK293 Cells
  • Humans
  • Indole Alkaloids / analysis
  • Indole Alkaloids / isolation & purification
  • Indole Alkaloids / pharmacokinetics
  • Indole Alkaloids / pharmacology
  • Male
  • Mass Spectrometry / methods
  • Oxindoles
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacokinetics
  • Plant Extracts* / pharmacology
  • Prostate / cytology*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Uncaria / chemistry*
  • Vasodilation / drug effects

Substances

  • Alkaloids
  • Indole Alkaloids
  • Oxindoles
  • Plant Extracts
  • corynoxeine
  • rhyncophylline