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. (14th October 2014)

• Record Type: Journal Article
• Authors: Zhao, Jia; Cheng, Yuan‐Yuan; Fan, Wen; Yang, Chuan‐Bin; Ye, Shui‐Fen; Cui, Wei; Wei, Wei; Lao, Li‐Xing; Cai, Jing; Han, Yi‐Fan; Rong, Jian‐Hui
• Is Part Of: CNS neuroscience & therapeutics. Volume 21:Number 1(2015)
• Page Start: 61
• Page End: 70
• Publication Date: 2014-10-14
• Subjects: Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.12334
• Languages: English
• ISSNs: 1755-5930

Abstract

<abstract abstract-type="main" id="cns12334-abs-0001"> <title>Summary</title> <sec id="cns12334-sec-0001" sec-type="section"> <title>Aim</title> <p>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.</p> </sec> <sec id="cns12334-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="cns12334-sec-0003" sec-type="section"> <title>Results</title> <p>Puerarin 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.</p> </sec> <sec id="cns12334-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>