Neurotrophic activity of obovatol on the cultured embryonic rat neuronal cells by increase of neurotrophin release through activation of ERK pathway.
Previously, we found that obovatol, a lignan compound isolated from Magnolia officinalis, has anti-cancer, anti-inflammatory, and anxiolytic effects. Recent studies showed that honokiol, magnolol, and 4-O-methylhonokiol, lignin compounds isolated from the Magnolia family have neurotrophic activity. In this study, we examined whether or not obovatol also exhibits neurite-promoting effects on rat embryonic neuronal cells. Obovatol increased neurite outgrowth in a concentration-dependent manner. Consistent with the neurite outgrowth effect, the expression of neurite differentiation markers also increased in response to obovatol. We also found that obovatol increased levels of NGF and BDNF released into the culture medium. In addition, the combination of low concentrations of obovatol (1 and 2 μM) with NGF (50 ng/ml) or with BDNF (10 ng/ml) greatly enhanced neurite outgrowth. Subsequently, we found that obovatol increased phosphorylation of ERK. However, the neurite outgrowth, and NGF and BDNF release induced by obovatol were prevented by an ERK-specific inhibitor. These results suggest that obovatol promotes neurite outgrowth due to the increased release of neurotrophic factors via activation of the ERK pathway.
Lee
Yong Kyoung
YK
College of Pharmacy, Chungbuk National University, 12 Geashin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
Song
Ju Kyoung
JK
Choi
Im Seop
IS
Jeong
Jae Hwang
JH
Moon
Dong Cheul
DC
Yun
Yeo Pyo
YP
Han
Sang Bae
SB
Oh
Ki-Wan
KW
Hong
Jin Tae
JT
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex; D055808:Drug Discovery; D004622:Embryo, Mammalian; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D009994:Osmolar Concentration; D010647:Phenyl Ethers / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000943:Antigens, Differentiation; D001713:Biphenyl Compounds; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D010647:Phenyl Ethers; D047428:Protein Kinase Inhibitors; C036795:obovatol; D020932:Nerve Growth Factor