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 Aβ 1-42 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.
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In APP/PS1 transgenic mice, geniposide ameliorates memory deficits by suppressing oxidative damage, mitochondrial function, and MAPK signaling overactivation.
“In APP/PS1 transgenic mice, the treatment with geniposide ameliorates memory deficits by significantly suppressing oxidative damage, mitochondrial function, and MAPK signaling overactivation (Lv et al., 2014; Zhao et al., 2017)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Zhao et al., 2017
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- Authors
- Zhao, C., Zhang, H., Li, H., Lv, C., Liu, X., Li, Z., Xin, W., Wang, Y., & Zhang, W.
- Affiliations
- Beijing Normal University (CN)
- Corresponding author
- Zhang, Wensheng
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 116
- Pages
- 18-29
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2560394177
- Cited by
- 59
- References
- 59
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 12 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 3
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81274118)
- Key New Drug Creation and Development Program of China (2012ZX09103-201)
- Fundamental Research Funds for the Central Universities (2015KJJCA05)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- geniposide, Alzheimer's disease, cognitive impairment, cholinergic deficit, amyloid-beta deposition, RAGE, MAPK signaling, APP/PS1 mice, cholinergic neurotransmission, acetylcholinesterase, choline acetyltransferase, hippocampus, memory enhancement, neuroprotection
- MeSH terms
- Receptor for Advanced Glycation End Products, Alzheimer Disease, Amyloidosis, Animals, Brain, Cognition Disorders, Disease Models, Animal, Dose-Response Relationship, Drug, Male, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Peptide Fragments, Amyloid beta-Peptides, Neuroprotective Agents, Nootropic Agents, MAP Kinase Signaling System, Iridoids
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