Neurite outgrowth induced by spicatoside A, a steroidal saponin, via the tyrosine kinase A receptor pathway

Eur J Pharmacol. 2009 Oct 12;620(1-3):9-15. doi: 10.1016/j.ejphar.2009.08.016. Epub 2009 Aug 18.

Abstract

Although nerve growth factor (NGF) therapy is an available option for the treatment of Alzheimer's disease, several limitations exist in its medical application. In the present study, we examined the neurotrophic effects of spicatoside A isolated from Liriope platyphylla on PC12 cells as well as the mechanisms involved in this process. Spicatoside A (10 microg/mL) induced neurite outgrowth similar to NGF (50 ng/mL). Furthermore, spicatoside A, a steroidal saponin, activated extracellular signal-regulated kinase 1/2 (ERK 1/2) and phosphatidylinositol 3-kinase (PI 3-kinase/Akt) via tyrosine receptor kinase A (TrkA), which is responsible for the induction of the neuritic process. The effects of NGF and spicatoside A on neurite outgrowth disappeared in TrkA knockdown PC12 cells by siRNA. In conclusion, neuritogenic effects resulting from spicatoside A may be involved in TrkA activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Enzyme Activation / drug effects
  • Glucosides / chemistry
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Magnoliopsida / chemistry
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Monoterpenes / chemistry
  • Monoterpenes / isolation & purification
  • Monoterpenes / pharmacology*
  • Nerve Growth Factor / metabolism
  • Neurites / drug effects*
  • Neurites / metabolism*
  • PC12 Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Rats
  • Receptor, trkA / metabolism*
  • Saponins / chemistry
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Signal Transduction / drug effects*
  • Steroids / chemistry*
  • Steroids / isolation & purification
  • Steroids / pharmacology

Substances

  • 5-(1-(glucopyranosyloxymethyl)ethenyl)-2-methyl-2-cyclohexen-1-one
  • Cyclic AMP Response Element-Binding Protein
  • Glucosides
  • Monoterpenes
  • Saponins
  • Steroids
  • Nerve Growth Factor
  • Phosphatidylinositol 3-Kinases
  • Receptor, trkA
  • Mitogen-Activated Protein Kinase 3