Effects of Dihuangyinzi on behaviors and RAGE/p38 pathway in APP/PS1 mice

Objective To investigate the effects of Dihuangyinzi(DHYZ) on behaviors and RAGE/p38 pathway in APP/PS1 mice. Method Twenty APP/PS1 dementia mice were randomly divided into model group(n=10) and Chinese medicine group(n=10). The blank group was C57 BL/6 J normal mouse(n=10). The mice in Chinese medicine group were intragastric administration with DHYZ (9.75 g·kg-1·d-1). The mice in model group and blank group were treated with distilled water.After 30 days, the abilities of learning and memory of mice were detected by Morris water maze. The expression of amyloid-beta1-42(Aβ1-42) in the hippocampus and cortex was detected by immunohistochemistry. Reactive oxygen species of brain tissue were detected by DCFH-DA methods in the brain of APP/PS1 mice. Gene expression level of receptor for advanced glycation end products(RAGE) was measured by real-time polymerase chain reaction (RT-PCR) in the cortex and hippocampus of APP/PS1 mice.The expression of phospho-mitogen-activated protein kinases (p38) was analyzed with Western blot and immunofluorescence analysis in the cortex and hippocampus of APP/PS1 mice. Results Behavioral results showed that DHYZ significantly increased the distance((23.088±7.083)cm) and residence time((1.961±1.230)s)of effective area in Morris water maze on the fifth day(P<0.05, P<0.01)and remarkably increased the number of effective area crossings((1.607±0.405) times) and plats((0.893±0.283) times) in Morris water maze on the fifth day(P<0.01, P<0.05). DHYZ also significantly reduced the intracelluar ROS level(122.611±7.630) in the brain(P<0.01), and DHYZ could depress the expression of RAGE(1.467±0.081, 7.983±0.136) and phosphorylation of p38 (0.376±0.026, 0.538±0.016)in the cortex and hippocampus of APP/PS1 mice(P<0.01, P<0.05). Conclusions The results demonstrate that DHYZ can partly improve memory impairment of APP/PS1 mice by the inhibition of RAGE/p38 pathway. Key words: Dihuangyinzi; Alzheimer’s disease; APP/PS1 double transgenic dementia mouse; Spatial probe; RAGE/p38 pathway