Nardosinone, a novel enhancer of nerve growth factor in neurite outgrowth from PC12D cells.
We isolated nardosinone as a neuritogenic substance from Nardostachys chinensis. Nardosinone did not exhibit the neurotrophic activity but caused a marked enhancement of the nerve growth factor (NGF)-mediated neurite outgrowth from PC12D cells. Nardosinone-induced enhancement of the NGF-action was completely blocked by PD98059, a representative mitogen activated protein kinase (MAPK) kinase inhibitor. The microscopic observations indicated that the neurites in response to nardosinone and NGF were quite long and were generally extended to the neighboring cells. These results suggest that nardosinone enhances the NGF-induced neurite outgrowth from PC12D cells probably by amplifying an up-stream step of MAPK kinase in the NGF receptor-mediated intracellular signaling pathway.
Li
P
P
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Matsunaga
K
K
Yamamoto
K
K
Yoshikawa
R
R
Kawashima
K
K
Ohizumi
Y
Y
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D000081223:Polycyclic Sesquiterpenes; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D009414:Nerve Growth Factors; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C011513:nardosinone; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one