Ginsenoside Rg1 facilitates neural differentiation of mouse embryonic stem cells via GR-dependent signaling pathway.
Ginsenoside Rg1, a steroidal saponin of high abundance in ginseng, possesses the neuroprotective effects. In this study, we tried to explore the effect of Rg1 on promoting differentiation of mouse embryonic stem (ES) cells towards the neuronal lineage and its potential role involved in glucocorticoid receptor (GR) activation. Rg1 treatment induced a remarkable increase in the population of neuron-like cells in a time-dependent manner. More than 80% of Rg1-treated embryoid bodies (EBs) differentiated into neuron-like cells on d 8+10. Furthermore, the gradually increased protein expression of neurofilament (NEFM) and β-tubulin III (a neuronal specific protein) was determined. GR expression gradually increased during the differentiation course. RU486, an antagonist of GR, could efficiently block the neurogenesis-promoting activity of Rg1. On the other side, Rg1 stimulated the phosphorylation of ERK1/2 and Akt at different time points through GR activation-dependent mechanisms. Treatment of both U0126 (an inhibitor of MEK) and LY294002 (an inhibitor of PI3 K), hampered the neuronal differentiation induced by Rg1. Meantime, U0126 further decreased Rg1-induced p-Akt expression. In conclusion, Rg1 possesses the effects on inducing differentiation of mouse ES cells into neurons in vitro via the GR-MEK-ERK1/2-PI3 K-Akt signaling pathway.
Division of Cardio-Cerebral Vascular and Hepatic Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Jiaying
J
Wu
Zongfu
Z
Pan
Meiyuan
M
Cheng
Yuanyuan
Y
Shen
Hao
H
Yu
Qiongyue
Q
Wang
Yijia
Y
Lou
D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D036145:Ginsenosides / Q000494:pharmacology*; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
D002070:Butadienes; D002491:Central Nervous System Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D007381:Intermediate Filament Proteins; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D009419:Nerve Tissue Proteins; D064231:Nestin; D009570:Nitriles; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011965:Receptors, Glucocorticoid; C577485:Nes protein, mouse; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C035054:ginsenoside Rg1