1. Huannao Yicong Formula () regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice.
- Author
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Wang ZY, Liu JG, Wei Y, Liu MX, Wang Q, Liang L, Yang HM, and Li H
- Subjects
- Animals, Cyclic AMP Response Element-Binding Protein genetics, Cyclic AMP Response Element-Binding Protein metabolism, Drugs, Chinese Herbal therapeutic use, Endopeptidases metabolism, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus drug effects, Hippocampus pathology, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Immunohistochemistry, Learning drug effects, Male, Membrane Proteins, Memory Disorders drug therapy, Memory Disorders genetics, Mice, Inbred C57BL, Mice, Transgenic, Presenilin-2 metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Signal Transduction drug effects, Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Protein Precursor metabolism, Drugs, Chinese Herbal pharmacology, Endopeptidases genetics, Gene Expression Regulation drug effects, Hippocampus metabolism, Presenilin-1 metabolism, Presenilin-2 genetics
- 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), Aβ
1-40 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., 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 , Aβ1-42 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 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.- Published
- 2017
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