title: Emodin induces neurite outgrowth through PI3K/Akt/GSK-3β-mediated signaling pathways in Neuro2a cells.
abstract: In this study, a neurite outgrowth-inducing substance was isolated from the ethylacetate extract of the Polygonum multiflorum roots and identified as emodin by gas-liquid chromatography-mass spectrometry and (1)H NMR and (13)C NMR. Emodin displayed remarkable neurite outgrowth-inducing activity in Neuro2a cells, as demonstrated by morphological changes and immunocytochemistry for class III β-tubulin. Emodin exhibited a stronger neutrophic activity than retinoic acid (RA) known as inducer of neurite outgrowth in Neuro2a cells. Emodin treatment resulted in marked increases in phosphorylation of Akt a direct downstream signaling molecule of phosphatidylinositol 3-kinase (PI3K), but upstream of glycogen synthase kinase-3β (GSK-3β) and cAMP response element-binding protein (CREB). These augmentations and neurite-bearing cells induced by emodin were remarkably reduced by the addition of PI3K inhibitor LY294002. These results demonstrate that emodin induces neuronal differentiation of Neuro2a cells via PI3K/Akt/GSK-3β pathway.
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan 604-714, South Korea.
authors.forename: Shin-Ji
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Horticultural Bioscience, Pusan National University, Miryang 627-706, South Korea.
authors.forename: Mei Ling
authors.initials: ML
authors.lastname: Jin
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan 604-714, South Korea.
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: An
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan 604-714, South Korea.
authors.forename: Kyoung-Sook
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Horticultural Bioscience, Pusan National University, Miryang 627-706, South Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Ko
authors.affiliation: Research Center for Anti-Aging Technology Development, Busan National University, Busan 609-735, South Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Horticultural Bioscience, Pusan National University, Miryang 627-706, South Korea. Electronic address: ywchoi@pusan.ac.kr.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Choi
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan 604-714, South Korea. Electronic address: yclee@dau.ac.kr.
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004642:Emodin / Q000302:isolation & purification / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry; D028502:Polygonum / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010936:Plant Extracts; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D004642:Emodin
keywords: Emodin; Neurite outgrowth; Neuro2a cells; Neuronal differentiation; PI3K/Akt/GSK-3β pathway