Huannao Yicong Formula (还脑益聪方) regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice

Zhi-yong Wang; Jian-gang Liu; Yun Wei; Mei-xia Liu; Qi Wang; Lin Liang; Hui-min Yang; Hao Li

doi:10.1007/s11655-017-2402-3

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Huannao Yicong Formula (还脑益聪方) regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice

Updated：2021-08-27

- Huannao Yicong Formula (还脑益聪方) regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice
- Chinese Journal of Integrative Medicine Vol. 23, Issue 4, Pages: 270-278(2017)
- Affiliations：
  
  1. Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences,Beijing,China
  2. Graduate School, Beijing University of Chinese Medicine,Beijing,China
  3. Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences,Beijing,China
  4. Geriatric Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine,Beijing,China
- Author bio：
- Funds：
  
  Supported by the National Natural Science Foundation of China (No. 81173383 and No. 81573819) and Beijing Municipal Science and Technology Plan "Ten Disease and Ten Medicine" (No. Z141100002214003)
- DOI：10.1007/s11655-017-2402-3
  CLC：
- Published：2017，
  
  Published Online：24 January 2017，
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Wang, Zy., Liu, Jg., Wei, Y. et al. Huannao Yicong Formula (还脑益聪方) regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice., Chin. J. Integr. Med. 23, 270–278 (2017). https://doi.org/10.1007/s11655-017-2402-3

Zhi-yong Wang, Jian-gang Liu, Yun Wei, et al. Huannao Yicong Formula (还脑益聪方) regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice. [J]. Chinese Journal of Integrative Medicine 23(4):270-278(2017)
Wang, Zy., Liu, Jg., Wei, Y. et al. Huannao Yicong Formula (还脑益聪方) regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice., Chin. J. Integr. Med. 23, 270–278 (2017). https://doi.org/10.1007/s11655-017-2402-3 DOI：

Zhi-yong Wang, Jian-gang Liu, Yun Wei, et al. Huannao Yicong Formula (还脑益聪方) regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice. [J]. Chinese Journal of Integrative Medicine 23(4):270-278(2017) DOI： 10.1007/s11655-017-2402-3.

摘要

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. 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)

Aβ1-40 and Aβ1-42 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 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. 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

Aβ1-42 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. 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.

Abstract

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. 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)

Aβ1-40 and Aβ1-42 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 1α (HIF-1α)

improving the number of platform crossing and swimming speed (P<0.01

P<0.05). HYF can decrease the levels of APP

Aβ1-40

and this may be one of the therapeutic mechanisms of HYF in Alzheimer’s disease.

关键词

Huannao Yicong FormulaAlzheimer’s diseaseγ-secretaseβ-amyloid

Keywords

Huannao Yicong FormulaAlzheimer’s diseaseγ-secretaseβ-amyloid

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Related Institution

National Key Lab of Available Utilization of Chemical Resources, Beijing University of Chemical Industry

Haici Medical Group of Qingdao City

Xiyuan Hospital, China Academy of Chinese Medical Sciences

Department of Geriatrics, Fuzhou General Hospital of Nanjing Military District

Research Center of Rehabilitation Science and Technology, School of Life Science and Technology, Xi’an Jiaotong University

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