Effects of deoxygedunin on Alzheimer-like pathologic dysfunction induced by D-galactose combined with AlCl.
10.12047/j.cjap.5732.2018.111
- Author:
Jian-Guo CHEN
1
;
Qi-Chuan JIANG
1
;
Bo WEN
1
;
Ruo-Ya WANG
1
;
Ya-Geng WU
1
;
Xiang LI
1
Author Information
1. Head and Neck Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
D-galactose;
Tau protein;
amyloid β;
deoxygedunin;
rat
- MeSH:
Alzheimer Disease;
chemically induced;
Animals;
Disease Models, Animal;
Galactose;
Hippocampus;
Limonins;
Male;
Maze Learning;
Rats;
Rats, Sprague-Dawley
- From:
Chinese Journal of Applied Physiology
2018;34(6):496-500
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of Deoxygedunin on Aβ deposition, learning memory, and oxidative stress induced by D-galactose combined with AlCl in model rats with Alzheimer's disease and its possible mechanism.
METHODS:Male SD rats were randomly divided into three groups (=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 AlCl induced a significant increase in the escape latency compared with the control group (<0.05).Deoxygedunin could reverse the increase of the escape latency of the model group (<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 (<0.01), and the number of crossing platforms was declined (<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 (<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 (<0.01), the decrease of SOD and GSH-Px activities (<0.05) and the increase of the MDA content (<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 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 AlCl.
