Ginsenoside Rg1 attenuates amyloid-beta content, regulates PKA/CREB activity, and improves cognitive performance in SAMP8 mice.
It is well established that the presence of soluble amyloid-beta protein (Abeta) correlates with the severity of dementia in Alzheimer's disease (AD). Several lines of evidence indicate that cyclic AMP responsive element binding protein (CREB) and protein kinase A (PKA) are involved in soluble Abeta-trigged disruption of synaptic plasticity in early AD. Previously we demonstrated the beneficial effects of ginsenoside Rg1 on Abeta-induced neuronal insult. Therefore, in the present study, we examined the effects of long-term consumption of Rg1 on the cerebral Abeta content and PKA/CREB signaling molecules, as well as cognitive performance in senescence-accelerated mouse prone 8 (SAMP8). Notably, a significant dose-dependent reduction of soluble Abeta(1-40) was shown in the hippocampus of SAMP8 mice after administration with ginsenoside Rg1 for 3 months. Furthermore, Rg1 treatment resulted in a significant decrease of hippocampal PKA RIIalpha level (isoform IIalpha of the regulatory subunit of PKA). In contrast, phospho-CREB and brain derived neurotrophic factor (BDNF) levels were dramatically increased in the hippocampus of SAMP8 treated with Rg1. Additionally, administration of ginsenoside Rg1 consequently improved learning and memory outcomes in SAMP8 mice. These data suggest that long-term consumption of ginsenoside Rg1 may delay cognitive decline, associated with significant effects on Abeta generation, PKA/CREB activity, as well as BDNF content in the brain. These data provide further support for the therapeutic or intervention potency of ginsenoside Rg1 in the early stage of AD.
Shi
Yan-Qing
YQ
Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China.
Huang
Tian-Wen
TW
Chen
Li-Min
LM
Pan
Xiao-Dong
XD
Zhang
Jing
J
Zhu
Yuan-Gui
YG
Chen
Xiao-Chun
XC
D000375:Aging / Q000187:drug effects; D000544:Alzheimer Disease / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice
D016229:Amyloid beta-Peptides; D002491:Central Nervous System Agents; D017362:Cyclic AMP Response Element-Binding Protein; D036145:Ginsenosides; D017868:Cyclic AMP-Dependent Protein Kinases; C035054:ginsenoside Rg1