[Effects of deoxygedunin on Alzheimer-like pathologic dysfunction induced by D-galactose combined with AlCl3].

ABSTRACT

OBJECTIVE: To investigate the effects of Deoxygedunin on Aß deposition, learning memory, and oxidative stress induced by D-galactose combined with AlCl3 in model rats with Alzheimer's disease and its possible mechanism. METHODS: Male SD rats were randomly divided into three groups (n=12)control group, model group (AD) and intervention group (AD+Deo). Morris water maze test was used to detect learning/memory and cognitive function in rats.Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in homogenate of hippocampus were detected by enzyme-linked immunosorbent assay (ELISA).Tau protein expression in rat cerebral cortex was detected by immunohistochemistry.Western blot was used to detect the expressions of extracellular signal regulated kinase 1(ERK1), protein kinase B (PKB) and tropomyosin-related kinase B (TrkB) on TrkB signaling pathway. RESULTS: The results of water maze test showed that D-galactose combined with AlCl3 induced a significant increase in the escape latency compared with the control group (P<0.05).Deoxygedunin could reverse the increase of the escape latency of the model group (P<0.05).On the 7th day after removal of the platform, the model group showed an increase in escape latency compared with the control group and the intervention group (P<0.01), and the number of crossing platforms was declined (P<0.05); The results of immunohistochemistry and ELISA showed that the expressions of Aß and tau protein in the model group were increased significantly compared with those of the control group (P<0.01).The activities of SOD and GSH-Px were decreased significantly and the content of MDA was increased significantly.Compared with the model group, Deoxygedunin could reverse the increase of the expressions of Aß and tau protein (P<0.01), the decrease of SOD and GSH-Px activities (P<0.05) and the increase of the MDA content (P<0.05).Western blot results showed that Deoxygedunin treatment reversed the decreased phosphorylation levels of TrkB, AKT and ERK1 in hippocampus of the model group. CONCLUSIONS: Supplement of Deoxygedunin can significantly reverse Aß deposition, oxidative stress and cognitive deficits by activating the TrkB signal transduction pathway, which suggest that Deoxygedunin may serve as a promising therapeutic candidate for attenuating AD-like pathological dysfunction induced by D-galactose combined with AlCl3.