Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model

There has been no extensive characterization of the effects of Ginsenoside Rg1, a pharmacological active component purified from the nature product ginseng, in an Alzheimer's disease mouse model. The well-characterized transgenic Alzheimer disease (AD) mice over expressing amyloid precursor protein (APP)/A beta (Tg mAPP) and nontransgenic (nonTg) littermates at age of 6 and 9 months were treated with Rg 1 for three months via intraperitoneal injection. Mice were then evaluated for changes in amyloid pathology, neuropathology and behavior. Tg mAPP treated with Rg1 showed a significant reduction of cerebral A beta, levels, reversal of certain neuropathological changes, and preservation of spatial learning and memory, as compared to vehicle-treated mice. Rg1 treatment inhibited activity of gamma-secretase in both Tg mAPP mice and B103-APP cells, indicating the involvement of Rg1 in APP regulation pathway. Furthermore, administration of Rg1 enhanced PKA/CREB pathway activation in mAPP mice and in cultured cortical neurons exposed to A beta or glutamate-mediated synaptic stress. Most importantly, the beneficial effects on attenuation of cerebral A beta accumulation, improvement in neuropathological and behavioral changes can be extended to the aged mAPP mice, even to 12-13 months old mice that had extensive amyloid pathology and severe neuropathological and cognitive malfunction. These studies indicate that Rg1 has profound multi-faced and neuroprotective effects in an AD mouse model. Rg1 induces neuroprotection through ameliorating amyloid pathology, modulating APP process, improving cognition, and activating PKA/CREB signaling. These findings provide a new perspective for the treatment of AD and demonstrate potential for a new class of drugs for AD treatment. (C) 2011 Elsevier B.V. All rights reserved.