Neurite outgrowth effect of 4-O-methylhonokiol by induction of neurotrophic factors through ERK activation.
Compounds isolated from Magnolia officinalis such as magnolol, honokiol and obovatol exhibit several pharmacological effects on CNS including depressant, anxiolytic and anticonvulsant effects, as well as neuroprotective effects against chemical and heat damages. Recently, honokiol was found to have a neurotrophic effect in fetal rat cortical neurons. In the present study, we show that 4-O-methylhonokiol, a novel compound from Magnolia officinalis, promotes neurite outgrowth in a concentration- dependent manner in rat embryonic neuronal cells. In parallel with the neurite outgrowth activity, the expression of neurite outgrowth marker proteins is also increased by treatment with 4-O-methylhonokiol. We also found that 4-O-methylhonokiol promotes the release of NGF and BDNF into cell culture medium. In addition, lower concentration of 4-O-methylhonokiol (1 and 2 lM) further enhanced neurite outgrowth and expression of neurite outgrowth marker proteins in the presence of NGF (50 ng/ml) or BDNF (10 ng/ml). Subsequently, we found that 4-O-methylhonokiol activates ERK in a concentration- dependent manner. However, the neurite outgrowth activity and the NGF and BDNF release induced by 4-O-methylhonokiol are suppressed by an ERK-specific inhibitor. These results suggest that 4-O-methylhonokiol has the ability to induce neurite outgrowth via the increase of neurotrophic factor levels through ERK activation.
Lee
Yong Kyoung
YK
College of Pharmacy, Chungbuk National University, 12 Geashin-dong, Heungduk-gu, Cheoungju, Chungbuk 361-763, Republic of Korea.
Choi
Im Seop
IS
Kim
Young Heui
YH
Kim
Ki Ho
KH
Nam
Sang Yun
SY
Yun
Young Won
YW
Lee
Moon Soon
MS
Oh
Ki Wan
KW
Hong
Jin Tae
JT
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D020932:Nerve Growth Factor / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C542058:4-O-methylhonokiol; D001713:Biphenyl Compounds; D019208:Brain-Derived Neurotrophic Factor; D017705:Lignans; D020932:Nerve Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases