Open AccessBotanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK 1/2 and PI 3K/Akt Signaling Pathways in the Neurite Extension Process
Author(s) -
Zhao Jia,
Cheng YuanYuan,
Fan Wen,
Yang ChuanBin,
Ye ShuiFen,
Cui Wei,
Wei Wei,
Lao LiXing,
Cai Jing,
Han YiFan,
Rong JianHui
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12334
Subject(s) - puerarin , mapk/erk pathway , protein kinase b , nerve growth factor , neurite , chemistry , pi3k/akt/mtor pathway , microbiology and biotechnology , pharmacology , signal transduction , pleiotrophin , neurotrophin , neuroprotection , biology , medicine , growth factor , biochemistry , receptor , pathology , alternative medicine , in vitro
Summary Aim 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.