Forsythia Ester Glycosides On The Ad Animal Models Of Learning And Memory Effect And Its Mechanism

Forsythia suspense has been used clinically in China for thousands of years, and is also one of common traditional Chinese medicines recorded in Chinese Pharmacopia. Forsythiaside(3,4-dihydroxy-β-phenethyl-O-α-L-rhamnopyranosyl-(1→6)-4-O-caffeoyl-β-D-glucopyranoside,C29H36O15), which is isolated from air-dried fruits of Forsythia suspense, has been proved to have anti-oxidation, anti-bacterial and anti-inflammatory activities. However, the studies of forsythiaside mainly focus on the effect in vitro, which block the clinical application of Forsythia suspense. In view of the anti-inflammatory and anti-oxidative properties, the aim of this present study is to investigate the neuroprotective effects and the possible mechanisms of forsythiaside on learning and memory deficits in different AD animal models, which will provid evidence for further clinical application of forsythiaside. Main research as follows:Firstly, the neuroprotective effect of forsythiaside was evaluated in three kind of cognitive impairment models (KM, BALB/C model induced by intrahippocampal injection of Aβ25～35and senescence-accelerated mouse prone8(SAMP8) model) using Morris water maze and step-through passive avoidance test. The results showed that oral administration of forsythiaside at doses of60,120and240mg/kg per day for45consecutive days had significantly reduced the latency time and increased escape rate, the crossing numbers and time spent in target quadrant in hidden-platform training and probe trial in morris water maze. In Step-through passive avoidance test, a significant decline in the time spent in dark chamber and number of errors whereas increase in latency was observed in forsythiaside-treated mice, indicating that forsythiaside could not only improve the spatial reference learning and memory, but also ameliorate the nonspatial learning and memory deficits in AD animal models.And then, after behavioral study, we investigated the possible mechanisms of forsythiaside relating to the suppression of oxidative stress, the reduction in inflammatory cytokines and the regulation on cholinergic as well as many other neurotransmitter systems. The results showed that forsythiaside significantly improved the activity of SOD, GSH-Px while inhibited the formation of MDA, NO, reduced the content of IL-1β, IL-6and the expression of β-amyloid peptide, suppressed the activity of AchE but activated the ChAT leading to more Ach formation. Furthermore, forsythiaside markedly increased the level of glutamic acid and descreased the level of gamma-aminobutyric acid. Finally, the changes of hippocampus neuron shape were observed by Hematein Eosin (HE) staining and Nissl technique. The results showed that the damage of hippocampal CA1region in AD mice was ameliorated by oral administration of forsythiaside. Specifically, the hippocamp CA1stucture in forsythiaside-treated mice was clear with only few scattered inflammatory cells, the shape of neuron was regular, the cell lined up in order, the layers were tight, and the number of Nissl body was increased, indicating that forsythiaside could improve the form and function of hippocampus neuron, and then keep the normal function of the central nervous system, which suggested that forsythiaside might be a useful treatment against Alzheimer’s disease.