Cellular and Molecular Neurobiology

, Volume 34, Issue 6, pp 913–923 | Cite as

Bilobalide Induces Neuronal Differentiation of P19 Embryonic Carcinoma Cells via Activating Wnt/β-Catenin Pathway

  • Mei Liu
  • Jingjing Guo
  • Juan Wang
  • Luyong Zhang
  • Tao PangEmail author
  • Hong LiaoEmail author
Original Research


Bilobalide, a natural product extracted from Ginkgo biloba leaf, is known to exhibit a number of pharmacological activities. So far, whether it could affect embryonic stem cell differentiation is still unknown. The main aim of this study was to investigate the effect of bilobalide on P19 embryonic carcinoma cells differentiation and the underlying mechanisms. Our results showed that bilobalide induced P19 cells differentiation into neurons in a concentration- and time-dependent manner. We also found that bilobalide promoted neuronal differentiation through activation of Wnt/β-catenin signaling pathway. Exposure to bilobalide increased inactive GSK-3β phosphorylation, further induced the nuclear accumulation of β-catenin, and also up-regulated the expression of Wnt ligands Wnt1 and Wnt7a. Neuronal differentiation induced by bilobalide was totally abolished by XAV939, an inhibitor of Wnt/β-catenin pathway. These results revealed a novel role of bilobalide in neuronal differentiation from P19 embryonic cells acting through Wnt/β-catenin signaling pathway, which would provide a better insight into the beneficial effects of bilobalide in brain diseases.


Bilobalide Neuronal differentiation P19 embryonic carcinoma cells Wnt/β-catenin signaling 


Amyloid β-peptide


Amyloid-β derived diffusible ligand


Adenomatous polyposis coli

bHLH protein

Basic helix-loop-helix protein


β-Nerve growth factor


Bovine serum albumin


2′,3′-Cyclic-nucleotide 3′-phosphodiesterase


Cyclic-AMP response element binding protein


Dimethyl sulfoxide


Embryonic stem cells


Glial fibrillary acidic protein


Glioma-associated oncogene family zinc finger


Glycogen synthase kinase-3 beta



P19 EC cells

P19 embryonic carcinoma cells


Retinoid acid


T-cell factor/lymphoid enhancer binding factor



This work was supported by National Natural Science Foundation of China (81271338, 81070967), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20130096110011), Natural Science Foundation of Jiangsu Province (BK20130653), the Fundamental Research Funds for the Central Universities (JKZD2013006), and 2011’ Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education.

Conflict of interest

The authors declare no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Neurobiology Laboratory, National Center for Drug ScreeningChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of EducationNanjingPeople’s Republic of China

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