Improvement effects of sinapic acid on Aβ42-induced injury of PC 12 cells and the mechanism / 中国药房

ABSTRACT

OBJECTIVE To s tudy the improvement effects of sinapic acid on Aβ42-induced injury of PC 12 cells and the mechanism. METHODS PC12 cells were divided into five groups ：control group ，model group ，sinapic acid group ，phosphoinositide- 3-kinase（PI3K）inhibitor group and extracellular signal-regulated kinase （ERK）inhibitor group. Each inhibitor group was added with LY 294002 and U 0126（10 μmol/L）for 1 h；except for control group ，other four groups were treated with 2 μmol/L Aβ42 for 24 h to replicate the Alzheimer ’s disease cell model ；except for control group and model group ，other three groups were added with 100 μmol/L sinapic acid respectively. After 24 hours of continuous culture ，survival rate of PC 12 cells was detected and the morphology of PC 12 cells was observed. The content of Aβ42，mRNA expression of cAMP response element binding protein （CREB），protein expression of cyclic adenosine monophosphate （cAMP），protein kinase A （PKA），CREB signaling pathway and phosphorylated CREB （p-CREB）were detected. RESULTS After treated with sinapic acid ，the survival rate of PC 12 cells，mRNA expression of CREB and protein expressions of cAMP ，PKA and p-CREB were increased significantly （P＜0.05），while the content of Aβ42 was decreased significantly （P＜0.05）；cell morphology was significantly improved and synapses increased. After intervened with PI 3K and ERK inhibitors ，the survival rate of PC 12 cells，above mRNA and protein expressions were reversed significantly （P＜0.05 or P＜0.01）；cell morphology was irregular ，the fragments increased ，and the synaptic connections decreased. CONCLUSIONS Sinapic acid can improve the survival rate of PC 12 cells injured by A β 42，improve cell （No.2021-KYYWF-0349） morphology and decrease the content of Aβ42，the mechanism of which may be associated with promoting the gene transcription of CREB ， and activating cAMP/PKA/CREB signaling pathway.