Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway.
Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), has been extensively used in traditional oriental medicine for the prevention and treatment of aging-related disorders for over 2000 years. Accumulating evidence suggests that ginsenosides such as Rg1 and Rb1, which are the pharmacologically active ingredients of ginseng, modulate neurotransmission. Synapsins are abundant phosphoproteins essential for regulating neurotransmitter release. All synapsins contain a short amino-terminal domain A that is highly conserved and phosphorylated by cAMP-dependent protein kinase (PKA), which plays a key role in regulating neurotransmitter release. In the present study, we demonstrated that both Rg1 and Rb1 increased neurotransmitter release in undifferentiated and differentiated PC12 cells. However, in the presence of the PKA inhibitor H89, Rg1, but not Rb1, still induced neurotransmitter release. Moreover, Rb1, but not Rg1, enhanced the phosphorylation of synapsins via PKA pathway. In summary, Rb1 promotes neurotransmitter release by increasing the phosphorylation of synapsins through the PKA pathway, whereas the similar effects observed with Rg1 are independent of the phosphorylation of synapsins.
Xue
Jian-Fei
JF
Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Medical College of Chinese People's Armed Police Force, Tianjin 300162, PR China.
Liu
Zhi-Jun
ZJ
Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Hu
Jin-Feng
JF
Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Chen
Hong
H
Medical College of Chinese People's Armed Police Force, Tianjin 300162, PR China.
Zhang
Jun-Tian
JT
Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Chen
Nai-Hong
NH
Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: chennh@imm.ac.cn.
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018697:Nootropic Agents / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016704:Synapsins / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D018377:Neurotransmitter Agents; D018697:Nootropic Agents; D016704:Synapsins; C442759:ginsenoside Rb1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C035054:ginsenoside Rg1