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

doi:10.12047/j.cjap.5732.2018.111

Abstract

Abstract: Objective: To investigate the effects of Deoxygedunin on Aβ 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 Aβ 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 Aβ 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.Conclusion: Supplement of Deoxygedunin can significantly reverse Aβ 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.

Key words: Alzheimer's disease, deoxygedunin, D-galactose, amyloid β, Tau protein, rat

CHEN Jian-guo, JIANG Qi-chuan, WEN Bo, WANG Ruo-ya, WU Ya-geng, LI Xiang. Effects of deoxygedunin on Alzheimer-like pathologic dysfunction induced by D-galactose combined with AlCl₃[J]. CJAP, 2018, 34(6): 496-500.

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

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