Ligusticum chuanxiong as a potential neuroprotectant for preventing serum deprivation-induced apoptosis in rat pheochromocytoma cells: functional roles of mitogen-activated protein kinases

J Ethnopharmacol. 2009 Apr 21;122(3):417-23. doi: 10.1016/j.jep.2009.02.011. Epub 2009 Feb 14.

Abstract

Ethnopharmacological relevance: Ligusticum chuanxiong (LC) as a common component in many traditional Chinese medicinal formulas and decoctions has been used to treat different central nervous diseases, suggesting a neuroprotective function.

Aim of the study: To investigate the functional roles of mitogen-activated protein kinases (MAPKs) in mediating the neuroprotection of LC.

Materials and methods: Different extractions of LC were applied with or without MAPK inhibitor to test their protection against serum deprivation-induced apoptosis in rat neuronal-like pheochromocytoma (PC12) cells as revealed by an MTT assay or Hoechst staining. Western blot was used to identify the activations of MAPKs.

Results: The most effective butanol extraction (LC-BuOH) was used in the following experiments. LC-BuOH reversed serum deprivation-induced decreased phosphorylation of extracellular signal-regulated kinase (ERK) and increased phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38, the family of MAPKs. A PKA inhibitor, blocked the protection of LC-BuOH and partially blocked LC-BuOH-induced alterations in MAPKs, suggesting that the LC-BuOH regulates MAPKs through both PKA-dependent and -independent pathways. Although PD 98059, an inhibitor of MEK which activates ERK, blocked LC-BuOH-induced ERK phosphorylation, it did not block the protection of LC-BuOH.

Conclusions: LC-BuOH mediates protection by suppressing JNK/p38 instead of activating ERK activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Drugs, Chinese Herbal / chemistry*
  • Flavonoids / metabolism
  • Ligusticum
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Protein Kinase Inhibitors / pharmacology
  • Rats
  • Rhizome

Substances

  • Drugs, Chinese Herbal
  • Flavonoids
  • Neuroprotective Agents
  • Plant Extracts
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinases
  • Adenosine
  • chuangxiong extract
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one