Cyclopamine bioactivity by extraction method from Veratrum californicum

Bioorg Med Chem. 2016 Aug 15;24(16):3752-7. doi: 10.1016/j.bmc.2016.06.017. Epub 2016 Jun 14.

Abstract

Veratrum californicum, commonly referred to as corn lily or Californian false hellebore, grows in high mountain meadows and produces the steroidal alkaloid cyclopamine, a potent inhibitor of the Hedgehog (Hh) signaling pathway. The Hh pathway is a crucial regulator of many fundamental processes during vertebrate embryonic development. However, constitutive activation of the Hh pathway contributes to the progression of various cancers. In the present study, a direct correlation was made between the extraction efficiency for cyclopamine from root and rhizome by eight methods, and the associated biological activity in Shh-Light II cells using the Dual-Glo® Luciferase Assay System. Alkaloid recovery ranged from 0.39 to 8.03mg/g, with ethanol soak being determined to be the superior method for obtaining biologically active cyclopamine. Acidic ethanol and supercritical extractions yielded degraded or contaminated cyclopamine with lower antagonistic activity towards Hh signaling.

Keywords: Cyclopamine; Hedgehog signaling; Steroidal alkaloids; Veratrum californicum.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomass
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / metabolism
  • Signal Transduction / drug effects
  • Veratrum / chemistry*
  • Veratrum Alkaloids / isolation & purification
  • Veratrum Alkaloids / pharmacology*

Substances

  • Hedgehog Proteins
  • Veratrum Alkaloids
  • cyclopamine