Huannao Yicong Formula(还脑益聪方) Regulates γ-Secretase Activity through APH-1 and PEN-2 Gene Ragulation

• 作 者: WANG Zhi-yong LIU Jian-gang WEI Yun LIU Mei-xia WANG Qi LIANG Lin YANG Hui-min LI Hao
• 机 构: Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing(100091), C
• 出 处: 中国结合医学杂志（英文版）
• 发表日期: 2017年4期
• 关键词: Huannao Yicong Formula Alzheimer's disease γ-secretase β-amyloid

Objective:To observe the effects of Huannao Yicong Formula(还脑益聪方, HYF) on learning and memory and it\'s regulating effect on γ,-secretase related anterior pharynx defective 1 (APH-1),presenilin enhancer-2 (PEN-2) signaling pathway,so as to discuss and further clarify the mechanism of HYF on Alzheimer\'s disease.Methods:Sixty APP/PS1 transgenic mice,randomly allocated into 4 groups,the model group,the donepezil group (0.65 mg/kg),HYF low-dose group (HYF-L,5.46 g/kg) and HYF high-dose group (HYF-H,10.92 g/kg),15 for each group.Another 15 C57BL/6J mice with the same age and same genetic background were allocated into the control group,proper dosage of drugs or distilled water were given by intragastric administration once daily for 12 weeks.After 12 weeks of administration,the learning and memory abilities of mice in each group was evaluated by the morris water maze test,amyloid precursor protein (APP),A β1-40 and A β1-42 levels in hippocampus were detected by enzyme-linked immunosorbent assay,γ-secretase was detected by dual luciferase assaying,the levels of APH-1a,hypoxia-inducible factor 1 α (HIF-1 α),cAMP response element-binding protein (CREB) and PEN-2 and their mRNA expression was measured by Western blot and real-time polymerase chain reaction.Resuits:HYF can ameliorate learning and memory deficits in APP/PS1 transgenic mice by decreasing the escape latency,improving the number of platform crossing and swimming speed (P＜0.01,P＜0.05).HYF can decrease the levels of APP,A β1-40,A β1-42 and the activity of γ-secretase in hippocampus of Alzheimer\'s disease model mice.HYF can down-regulate the levels of CREB and PEN-2 and the expression of their mRNA.Conclusion:HYF can improve the leaming and memory ability by inhibiting the activity of γ-secretase through the CREB/PEN-2 signaling pathway,and this may be one of the therapeutic mechanisms of HYF in Alzheimer\'s disease.