Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/35789
Title: Botanical drug Puerarin coordinates with nerve growth factor in the regulation of neuronal survival and Neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the Neurite Extension Process
Authors: Zhao, J
Cheng, YY
Fan, W
Yang, CB
Ye, SF
Cui, W
Wei, W
Lao, LX
Cai, J
Han, YF 
Rong, JH
Keywords: ERK1/2
Neuritogenesis
Nrf2/heme oxygenase-1
PI3K/Akt
Puerarin
Issue Date: 2015
Publisher: Wiley-Blackwell
Source: CNS neuroscience and therapeutics, 2015, v. 21, no. 1, p. 61-70 How to cite?
Journal: CNS neuroscience and therapeutics 
Abstract: Aim: Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process.
Methods: We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP-lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2, and HO-1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit. ResultsPuerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP-lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold.
Mechanistic studies revealed: (1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase-1 (HO-1) pathways; (2) ERK1/2, PI3K/Akt, and HO-1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF-induced neuritogenesis in a timing-dependent manner.
Conclusion: Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases.
URI: http://hdl.handle.net/10397/35789
ISSN: 1755-5930 (print)
1755-5949 (online)
DOI: 10.1111/cns.12334
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