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.

Platycodon grandiflorus Root Extract Improves Learning and Memory by Enhancing Synaptogenesis in Mice Hippocampus

“…Interestingly, we observed the activating action of PG on both neurite outgrowth and ERK signaling pathway in neuronal cells ( Figure 7 ). A large number of previous studies have shown the stimulating effects of ERK1/2 and natural products from plants on neurite outgrowth [ 56 , 57 , 58 , 59 , 60 ]. It has been reported that ginsenoside Rg1 and Rb1, and triterpenoid saponins, enhance the neurite outgrowth of hippocampal neurons by activating the ERK1/2 and PI3K/Akt pathways [ 56 , 57 ].…”

“…It has been reported that ginsenoside Rg1 and Rb1, and triterpenoid saponins, enhance the neurite outgrowth of hippocampal neurons by activating the ERK1/2 and PI3K/Akt pathways [ 56 , 57 ]. Ginsenoside Rd treatment also promotes the neurite outgrowth of PC12 cells by activating the MAPK/ERK and PI3K/Akt signaling proteins [ 60 ]. In human endothelial cells, pretreatment with ginsenoside Rg1 up-regulated glucocorticoid receptor dependent ERK phosphorylation [ 58 ].…”

Active ginseng components in cognitive impairment: Therapeutic potential and prospects for delivery and clinical study

“…The mechanism involved in prevention of TMT-induced cell apoptosis by Rd treatment is the regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 (Bax) and caspase-3 [ 76 ]. Moreover, Rd may promote neurite outgrowth in PC12 cells by upregulating growth-associated protein-43 expression through both extracellular signal-regulated kinase (ERK)- and adhesion related kinase-dependent signaling pathways [ 77 ].…”

Pre‑treatment with a combination of Shenmai and Danshen injection protects cardiomyocytes against hypoxia/reoxygenation‑ and H2O2‑induced injury by inhibiting mitochondrial permeability transition pore opening

“…The mechanisms underlying reperfusion injury are complex and multifactorial, with ROS generation, Ca 2+ overload, opening of the mPTP, endothelial dysfunction and pronounced inflammatory responses all implicated in causing the damage (31). Radix Ginseng Rubra, Radix Ophiopogonis and S. miltiorrhiza Bunge, which are included in YYH, have been investigated to determine their potential combined pharmaceutical properties, including anti-inflammatory, anti-oxidant, microcirculation promotion and cardioprotective abilities (32,33). In the clinic, it has been reported that YYH improved myocardial reperfusion injury following PCI in patients with acute myocardial infarction (18).…”