A natural diarylheptanoid promotes neuronal differentiation via activating ERK and PI3K-Akt dependent pathways. (10th September 2015)

• Record Type: Journal Article
• Authors: Tang, G.; Dong, X.; Huang, X.; Huang, X.-J.; Liu, H.; Wang, Y.; Ye, W.-C.; Shi, L.
• Is Part Of: Neuroscience. Volume 303(2015)
• Page Start: 389
• Page End: 401
• Publication Date: 2015-09-10
• Subjects: BrdU bromodeoxyuridine -- DG dentate gyrus -- DIV day in vitro -- ERK extracellular signal-regulated kinase -- JNK c-Jun NH2-terminal kinase -- MAPK mitogen-activated protein kinase -- MEK MAPK/ERK kinase -- MTT 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide -- NSPCs neural stem/progenitor cells -- PI3K phosphoinositide 3-kinase -- RA retinoic acid -- TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; adult neurogenesis -- dentate gyrus -- natural product -- neurite outgrowth -- neuronal differentiation -- neuronal polarization; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.07.019
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Three natural diarylheptanoids possessed neurogenic and neuritogenic activities. Cpd 1 promoted differentiation of neuroblastoma cells and hippocampal neurons. Cpd 1 promoted differentiation/maturation of adult-born dentate neural progenitors. Pro-differentiation activity of Cpd 1 was dependent on ERK and PI3K-Akt pathways. Abstract: Neuronal differentiation is a critical developmental process that determines accurate synaptic connection and circuit wiring. A wide variety of naturally occurring compounds have been shown as promising drug leads for the generation and differentiation of neurons. Here we report that a diarylheptanoid from the plant Alpinia officinarum, 7-(4-hydroxyphenyl)-1-phenyl-4 E -hepten-3-one (Cpd 1), exhibited potent activities in neuronal differentiation and neurite outgrowth. Cpd 1 induced differentiation of neuroblastoma Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of cultured hippocampal neurons. Moreover, Cpd 1 promoted neurite extension in both Neuro-2a cells and neurons. We showed that the effects of Cpd 1 on neuronal differentiation and neurite growth were specifically dependent on the activation of extracellular signal-regulated kinases (ERKs) and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways. Importantly, intraperitoneal administration of Cpd 1 promoted the differentiation of new-born progenitor cells into mature neurons in the adult hippocampal dentate gyrus. Collectively, this study identifies a naturally occurring diarylheptanoid with beneficial effects on neuronal differentiation and neurite outgrowth in vitro and in vivo .