title: Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice.
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 Aβ1-42induced 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.affiliation: 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.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Haijing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Cui
authors.initials: C
authors.lastname: Lv
authors.affiliation: 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.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100875, China. Electronic address: li_zhi@mail.bnu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xin
authors.affiliation: 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.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000686:Amyloidosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D039823:Iridoids / Q000737:chemistry / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018697:Nootropic Agents / Q000737:chemistry / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism
chemical_list: C000593873:Ager protein, mouse; D016229:Amyloid beta-Peptides; D039823:Iridoids; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; C075222:amyloid beta-protein (1-42); C007835:geniposide
keywords: Acetylcholine; Alzheimer's disease; Amyloid β; Cognition; Geniposide; Receptor for advanced glycation end products