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Neurite Outgrowth Effect of 4-O-methylhonokiol by Induction of Neurotrophic Factors Through ERK Activation

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Abstract

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 μM) 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.

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Abbreviations

AD:

Alzheimer’s disease

BDNF:

Brain-derived neurotrophic factor

CNS:

Central nervous system

ERK:

Extracellular signal-regulated kinases

MAPK:

Mitogen-activated protein kinase

NGF:

Nerve growth factor

SDS–PAGE:

Sodium dodecyl sulphate–polyacrylamide gel electrophoresis

TBI:

Traumatic brain injury

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Acknowledgments

This work was supported by a research grant from Bioland Ltd., Korea (2008–2009), by a Korea Research Foundation Grant funded by the Korean Government (KRF-2008-005-J02801), and by a Korea Science and Engineering Foundation (KOSEF) grant funded by Korea Government (MOST) (K13-2008-001-00000-00).

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Authors and Affiliations

  1. College of Pharmacy, Chungbuk National University, 12 Geashin-dong, Heungduk-gu, Cheoungju, Chungbuk, 361-763, Republic of Korea

    Yong Kyoung Lee, Im Seop Choi, Ki Wan Oh & Jin Tae Hong

  2. Medical Research Center, Chungbuk National University, 12 Geashin-dong, Heungduk-gu, Cheoungju, Chungbuk, 361-763, Republic of Korea

    Im Seop Choi & Jin Tae Hong

  3. College of Veterinary Medicine, Chungbuk National University, 12 Geashin-dong, Heungduk-gu, Cheoungju, Chungbuk, 361-763, Republic of Korea

    Sang Yun Nam & Young Won Yun

  4. College of Agriculture, Life and Environment, Chungbuk National University, 12 Geashin-dong, Heungduk-gu, Cheoungju, Chungbuk, 361-763, Republic of Korea

    Moon Soon Lee

  5. Bioland R&D Center, 39-4 Songjeong, Byeongcheon, Cheonan, Chungnam, Republic of Korea

    Young Heui Kim & Ki Ho Kim

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  1. Yong Kyoung Lee
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Correspondence to Jin Tae Hong.

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Lee, Y.K., Choi, I.S., Kim, Y.H. et al. Neurite Outgrowth Effect of 4-O-methylhonokiol by Induction of Neurotrophic Factors Through ERK Activation. Neurochem Res 34, 2251–2260 (2009). https://doi.org/10.1007/s11064-009-0024-7

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  • DOI: https://doi.org/10.1007/s11064-009-0024-7

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