Ginsenoside Rd Attenuates Tau Phosphorylation in Olfactory Bulb, Spinal Cord, and Telencephalon by Regulating Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5

OBJECTIVE: Ginseng is a plant of the family Acanthopanaceae. It has been used for thousands of years in China. It is known as the king of hundred herbs. It was recorded first in Shennong Baicao Jing. It has been found that ginsenoside Rd is a neuroprotective agent. This article aims to explore the protective roles of ginsenoside Rd in Alzheimer's disease. Rd, a Chinese herb, may be a promising treatment drug for Alzheimer′s disease (AD) and is also reported to be related to several pathological changes, including the deposition of Aβ and tau hyperphosphorylation in AD as it decreases the deposition of tau hyperphosphorylation in APP transgenic mice. METHODS: In this study, APP transgenic mice were pretreated with 10 mg/kg Rd for six months, and the effect of Rd on neuropathological deficits in the olfactory bulb, spinal cord, and telencephalon of APP transgenic mice was investigated. The phosphorylation levels of tau (S199/202, S396, S404, and Tau5) and the activities of the proteins glycogen synthase kinase 3β (Tyr216) and cyclin-dependent kinase 5 (P25/P35) were measured. RESULTS: The pretreatment of Rd effectively decreased the production and deposition of hyperphosphorylated tau (S199/202, S396, and S404) protein by depressing the expression of glycogen synthase kinase 3β (GSK-3β/Tyr216) and cyclin-dependent kinase 5 (CDK5/P25). CONCLUSION: These findings suggest that ginsenoside Rd could improve the pathological changes of AD in the olfactory bulb, spinal cord, and telencephalon, which further demonstrated the potential therapeutic effect of Rd in early AD.