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


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


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.
Lin
Yun-Lian
YL
National Research Institute of Chinese Medicine, Taipei, Taiwan.
Wang
Guei-Jane
GJ
Huang
Chuen-Lin
CL
Lee
Yi-Chao
YC
Liao
Wei-Chen
WC
Lai
Wen-Lin
WL
Lin
Yen-Ju
YJ
Huang
Nai-Kuei
NK
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005419:Flavonoids / Q000378:metabolism; D030004:Ligusticum; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D027343:Rhizome
D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases; D000241:Adenosine; C101574:chuangxiong extract; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one