Neurotrophic and cytoprotective action of puerarin in PC12 cells via sequentially activating ERK1/2 pathway and inducing HO-1 expression

Abstract

Parkinson’s disease (PD) is a common life-threatening neurodegenerative disorder characterized by progressive and selective loss of dopaminergic (DA) neurons. Current treatments are largely symptomatic and mainly target dopamine level in the degenerating nigrostriatal region. Encouragingly, many botanicals are known to prevent/delay the ongoing neurodegeneration and even help functional recovery in PD. We recently found that puerarin, a neuroprotective C-glycosyl isoflavonoid from the herb Gegen (Radix Puerariae), potentiated nerve growth factor (NGF)-induced neurite outgrowth in dopaminergic PC12 cells in a concentration- and time-dependent manner. By investigating the potential mechanisms underlying the neurotrophic and cytoprotective action of puerarin, we found: (1) puerarin strongly activated pro-survival protein kinases ERK1/2 and, to a lesser extent, PI3K/Akt; (2) puerarin effectively inhibited pro-apoptotic activation of NF-κB pathway; (3) induced heme oxygenase-1 (HO-1) expression. Importantly, inhibition of ERK1/2 and HO-1 by specific inhibitors could diminish the neurotrophic and cytoprotective action of puerarin in PC12 cells. Thus, these results suggest that puerarin may potentiate the neurotrophic activity of NGF and enhance the cell survival via regulating the cross-talk between protein kinase ERK1/2, NF-κB pathways and HO-1 activity. Importantly, this study will promote the development of novel non-steroid medicines for not only protecting neurons from degeneration but also promoting adult neurogenesis for functional recovery in PD.