title: Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.
abstract: Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.
authors: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China. wusongdi@gmail.com.|Department of Neurology, First Hospital of Xi'an, Xi'an 710002, China. wusongdi@gmail.com.
authors: Song-Di
authors: SD
authors: Wu
authors: Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China. xiafeng@fmmu.edu.cn.
authors: Feng
authors: F
authors: Xia
authors: Department of Neurology, First Hospital of Xi'an, Xi'an 710002, China. mag_little@163.com.
authors: Xue-Mei
authors: XM
authors: Lin
authors: Department of Neurology, First Hospital of Xi'an, Xi'an 710002, China. duankangli2016@sina.com.
authors: Kang-Li
authors: KL
authors: Duan
authors: Department of Neurology, First Hospital of Xi'an, Xi'an 710002, China. wjhy1234@163.com.
authors: Fang
authors: F
authors: Wang
authors: Department of Neurology, First Hospital of Xi'an, Xi'an 710002, China. luql525@163.com.
authors: Qing-Li
authors: QL
authors: Lu
authors: Department of Neurology, First Hospital of Xi'an, Xi'an 710002, China. neurocao@163.com.
authors: Huan
authors: H
authors: Cao
authors: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China. qianyh38@mail.xjtu.edu.cn.
authors: Yi-Hua
authors: YH
authors: Qian
authors: Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China. biomidas@163.com.
authors: Ming
authors: M
authors: Shi
mesh_terms: D000818:Animals; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D055495:Neurogenesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: D019922:GAP-43 Protein; D036145:Ginsenosides; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C049863:ginsenoside Rd
keywords: AKT; ERK; GAP-43; PC12 cells; ginsenoside Rd; neurite outgrowth