title: Huannao Yicong Formula () regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice.
abstract: OBJECTIVE
  To observe the effects of Huannao Yicong Formula (, 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), Aβ1-40and Aβ1-42levels 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 1α (HIF-1α), cAMP response element-binding protein (CREB) and PEN-2 and their mRNA expression was measured by Western blot and real-time polymerase chain reaction.
  
  
  RESULTS
  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, Aβ1-40, Aβ1-42and 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.
  
  
  CONCLUSIONS
  HYF can improve the learning 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.
authors.affiliation: Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.|Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
authors.forename: Jian-Gang
authors.initials: JG
authors.lastname: Liu
authors.affiliation: Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
authors.forename: Mei-Xia
authors.initials: MX
authors.lastname: Liu
authors.affiliation: Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liang
authors.affiliation: Geriatric Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Yang
authors.affiliation: Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. xyhplihao1965@126.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007858:Learning / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins; D008569:Memory Disorders / Q000188:drug therapy / Q000235:genetics; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000378:metabolism*; D053766:Presenilin-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2; D012333:RNA, Messenger; C581246:huannao yicong; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; C498194:Aph1a protein, mouse
keywords: Alzheimer’s disease; Huannao Yicong Formula; β-amyloid; γ-secretase