title: Multi-faced neuroprotective effects of geniposide depending on the RAGE-mediated signaling in an Alzheimer mouse model.
abstract: The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to Aβ-induced pathogenic responses. Geniposide, a pharmacologically active component purified from gardenia fruit, could attenuate the oligomeric Aβ(1-42)-induced inflammatory response by blocking the ligation of Aβ to RAGE and suppressing the RAGE-mediated signaling in vitro. Here, we investigated whether geniposide can exert protective effects on the neuroinflammation and memory deficits in an Alzheimer's disease (AD) mouse model. The results indicate that geniposide treatment significantly suppresses RAGE-dependent signaling (activation of ERK and IκB/NF-κB), the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and cerebral Aβ accumulation in vivo. Furthermore, we demonstrate that geniposide augments synaptic plasticity by attenuating the Aβ-induced reduction of long-term potentiation and increasing the miniature excitatory postsynaptic current (mEPSC) amplitude and frequency in hippocampal neurons. In addition, the intragastric administration of geniposide improves learning and memory in APP/PS1 mice. Taken together, these studies indicate that geniposide has profound multifaceted neuroprotective effects in an AD mouse model. Geniposide demonstrates its neuroprotection by inhibiting inflammation, ameliorating amyloid pathology and improving cognition. Thus, geniposide may be a potential therapeutic agent for halting and preventing AD progression.
authors.affiliation: State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China; Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing 100088, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China. Electronic address: fullhouse1619@163.om.
authors.forename: Cui
authors.initials: C
authors.lastname: Lv
authors.affiliation: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing 100088, China. Electronic address: wangleisdqd@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China; Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing 100088, 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: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing 100088, China. Electronic address: yoskun520@yahoo.com.cn.
authors.forename: Shijun
authors.initials: S
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China; Department of Pharmacology and Toxicology, Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA. Electronic address: shidu@ku.edu.
authors.forename: Shirley ShiDu
authors.initials: SS
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China; Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing 100088, China. Electronic address: 229847000@qq.com.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China; Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing 100088, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China. Electronic address: zws@bnu.edu.cn.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D039823:Iridoids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D039823:Iridoids; D018696:Neuroprotective Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C007835:geniposide
keywords: APP/PS1 transgenic mice; Alzheimer's disease; Amyloid-β; Geniposide; Receptor for advanced glycation end products