Effects of Gypenosides on memory deficits in an MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA

Gynostemma pentaphyllum (GP) mainly contains approximately 90 dammarane-type triterperpene glycosides, which are named by gypenosides (GPS). This study investigated the effects of ethanol extract from GP (GP-EX) and GPS on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (MPTP-lesioned mice). MPTP (30 mg/kg/day, 5 days)-lesioned mice showed deficits of habit learning memory and spatial memory, which were further aggravated by treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) (25 mg/kg, 21 days). However, treatment with GP-EX (50 mg/kg, 21 days) or gypenosides (GPS) (50 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice treated with L-DOPA (25 mg/kg): GP-EX and GPS improved decreases in retention latency time of passive avoidance test and tyrosine hydroxylase-immunopositive cells and dopamine levels in the nigro striatum. GP-EX and GPS also reduced increases in retention transfer latency time of elevated plus-maze test and expression of N-methyl-D-aspartate (NMDA) receptor, and improved decreases in phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus in the same models. These results suggest that GP-EX and GPS ameliorate habit learning memory deficits by activating dopaminergic neurons and spatial memory deficits by modulating NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mice treated with L-DOPA. GP-EX and GPS may serve as an adjuvant phytonutrient for memory deficits in Parkinson's disease.