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Huannao Yicong Formula () 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. 2017 Apr; 23(4):270-278.CJ

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), Aβ1-40 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.

Authors+Show Affiliations

Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China.Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.Geriatric Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China.Geriatric Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. xyhplihao1965@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28120208

Citation

Wang, Zhi-Yong, et al. "Huannao Yicong Formula () 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, no. 4, 2017, pp. 270-278.
Wang ZY, Liu JG, Wei Y, et al. Huannao Yicong Formula () 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. 2017;23(4):270-278.
Wang, Z. Y., Liu, J. G., Wei, Y., Liu, M. X., Wang, Q., Liang, L., Yang, H. M., & Li, H. (2017). Huannao Yicong Formula () 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, 23(4), 270-278. https://doi.org/10.1007/s11655-017-2402-3
Wang ZY, et al. Huannao Yicong Formula () 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. 2017;23(4):270-278. PubMed PMID: 28120208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Huannao Yicong Formula () regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice. AU - Wang,Zhi-Yong, AU - Liu,Jian-Gang, AU - Wei,Yun, AU - Liu,Mei-Xia, AU - Wang,Qi, AU - Liang,Lin, AU - Yang,Hui-Min, AU - Li,Hao, Y1 - 2017/01/24/ PY - 2016/05/23/received PY - 2017/1/26/pubmed PY - 2017/4/25/medline PY - 2017/1/26/entrez KW - Alzheimer’s disease KW - Huannao Yicong Formula KW - β-amyloid KW - γ-secretase SP - 270 EP - 278 JF - Chinese journal of integrative medicine JO - Chin J Integr Med VL - 23 IS - 4 N2 - 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), Aβ1-40 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. SN - 1672-0415 UR - https://www.unboundmedicine.com/medline/citation/28120208/Huannao_Yicong_Formula____regulates_γ_secretase_activity_through_APH_1_and_PEN_2_gene_ragulation_pathways_in_hippocampus_of_APP/PS1_double_transgenic_mice_ L2 - https://dx.doi.org/10.1007/s11655-017-2402-3 DB - PRIME DP - Unbound Medicine ER -