In:
CNS Neuroscience & Therapeutics, Wiley, Vol. 21, No. 1 ( 2015-01), p. 61-70
Abstract:
Nerve growth factor ( NGF ) regulates neuronal survival and differentiation by activating extracellular signal‐regulated‐kinases ( ERK ) 1/2 and phosphoinositide‐3‐kinase ( PI 3K)/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 ERK 1/2 and PI 3K/Akt in neurite extension process. Methods We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP ‐lesioned mice and dopaminergic PC 12 cells. The effects of puerarin on ERK 1/2, Akt, Nrf2, and HO ‐1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit. Results Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP ‐lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC 12 cells by 〉 10‐fold. Mechanistic studies revealed: (1) puerarin rapidly activated ERK 1/2 and Akt, leading to the activation of Nrf2/heme oxygenase‐1 ( HO ‐1) pathways; (2) ERK 1/2, PI 3K/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 ERK 1/2 and PI 3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin‐related compounds in neurodegenerative diseases.
Type of Medium:
Online Resource
ISSN:
1755-5930
,
1755-5949
DOI:
10.1111/cns.2014.21.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2423467-9
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