title: A natural diarylheptanoid promotes neuronal differentiation via activating ERK and PI3K-Akt dependent 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-4E-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.
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China.
authors.forename: G
authors.initials: G
authors.lastname: Tang
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China.
authors.forename: X
authors.initials: X
authors.lastname: Dong
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Huang
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China. Electronic address: chyewc@gmail.com.
authors.forename: W-C
authors.initials: WC
authors.lastname: Ye
authors.affiliation: JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, Guangdong, China. Electronic address: sophielshi80@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D036381:Diarylheptanoids / Q000737:chemistry / Q000494:pharmacology*; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D036381:Diarylheptanoids; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D014212:Tretinoin; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3
keywords: adult neurogenesis; dentate gyrus; natural product; neurite outgrowth; neuronal differentiation; neuronal polarization