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Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice.
Neuropharmacology. 2017 04; 116:18-29.N

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and cholinergic defect are widely thought to be the underlying mechanism of learning and memory impairment. Geniposide, which is the main active component of the traditional Chinese herbal Gardenia jasminoides Ellis, elicits neuroprotective effects by alleviating inflammation responses and oxidative damages. In this study, we investigated the protective effect of geniposide on levels of cholinergic markers, RAGE, RAGE-dependent signalling pathways and amyloid accumulation in the APPswe/PS1dE9 AD model mouse. Geniposide suppressed MAPK signaling over-activation mediated by Aβ-RAGE interaction, resulting in reduced Aβ accumulation and amelioration of cholinergic deficits in the cerebral hippocampus. Furthermore, geniposide inhibited the toxic effect of oligomeric Aβ1-42 induced cholinergic deficit by increasing ChAT levels and activity but decreasing AChE activity in cultured primary hippocampal neurons. These results indicated that geniposide enhanced cholinergic neurotransmission, which likely contributes to its memory enhancing effect.

Authors+Show Affiliations

Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100875, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China. Electronic address: azkuuuu@sina.com.Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100875, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China. Electronic address: haijingzhang88@163.com.Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100875, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China. Electronic address: lihang8658@163.com.Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100875, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China; Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Shandong Academy of Science, Jinan 250014, China. Electronic address: fullhouse1619@163.com.Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China. Electronic address: lxl518518@163.com.Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China. Electronic address: li_zhi@mail.bnu.edu.cn.Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China; Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming 650000, China. Electronic address: 77580001@qq.com.Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100875, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China. Electronic address: 229847000@qq.com.Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100875, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China; Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming 650000, China. Electronic address: zws@bnu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27940040

Citation

Zhao, Chunhui, et al. "Geniposide Ameliorates Cognitive Deficits By Attenuating the Cholinergic Defect and Amyloidosis in Middle-aged Alzheimer Model Mice." Neuropharmacology, vol. 116, 2017, pp. 18-29.
Zhao C, Zhang H, Li H, et al. Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice. Neuropharmacology. 2017;116:18-29.
Zhao, C., Zhang, H., Li, H., Lv, C., Liu, X., Li, Z., Xin, W., Wang, Y., & Zhang, W. (2017). Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice. Neuropharmacology, 116, 18-29. https://doi.org/10.1016/j.neuropharm.2016.12.002
Zhao C, et al. Geniposide Ameliorates Cognitive Deficits By Attenuating the Cholinergic Defect and Amyloidosis in Middle-aged Alzheimer Model Mice. Neuropharmacology. 2017;116:18-29. PubMed PMID: 27940040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice. AU - Zhao,Chunhui, AU - Zhang,Haijing, AU - Li,Hang, AU - Lv,Cui, AU - Liu,Xiaoli, AU - Li,Zhi, AU - Xin,Wenfeng, AU - Wang,Yongyan, AU - Zhang,Wensheng, Y1 - 2016/12/06/ PY - 2016/05/20/received PY - 2016/11/30/revised PY - 2016/12/03/accepted PY - 2016/12/13/pubmed PY - 2018/5/10/medline PY - 2016/12/13/entrez KW - Acetylcholine KW - Alzheimer's disease KW - Amyloid β KW - Cognition KW - Geniposide KW - Receptor for advanced glycation end products SP - 18 EP - 29 JF - Neuropharmacology JO - Neuropharmacology VL - 116 N2 - Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and cholinergic defect are widely thought to be the underlying mechanism of learning and memory impairment. Geniposide, which is the main active component of the traditional Chinese herbal Gardenia jasminoides Ellis, elicits neuroprotective effects by alleviating inflammation responses and oxidative damages. In this study, we investigated the protective effect of geniposide on levels of cholinergic markers, RAGE, RAGE-dependent signalling pathways and amyloid accumulation in the APPswe/PS1dE9 AD model mouse. Geniposide suppressed MAPK signaling over-activation mediated by Aβ-RAGE interaction, resulting in reduced Aβ accumulation and amelioration of cholinergic deficits in the cerebral hippocampus. Furthermore, geniposide inhibited the toxic effect of oligomeric Aβ1-42 induced cholinergic deficit by increasing ChAT levels and activity but decreasing AChE activity in cultured primary hippocampal neurons. These results indicated that geniposide enhanced cholinergic neurotransmission, which likely contributes to its memory enhancing effect. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/27940040/Geniposide_ameliorates_cognitive_deficits_by_attenuating_the_cholinergic_defect_and_amyloidosis_in_middle_aged_Alzheimer_model_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(16)30555-X DB - PRIME DP - Unbound Medicine ER -