Geniposide Attenuates the Level of Aβ1-42 via Enhancing Leptin Signaling in Cellular and APP/PS1 Transgenic Mice
Abstract
An large body of evidence indicates that leptin has protective role against Alzheimer's disease, where it reduces β-amyloid (Aβ) production in both cell culture and animal models. Our previous studies revealed that geniposide could attenuate the production of Aβ 1-42 and antagonize the neurotoxicity of Aβ 1-42 in neurons. However, the mechanism that underlies these effects remains to be clarified. To investigate whether leptin signaling is involved in regulating the production of Aβ 1-42 by geniposide, we treated primary neurons with leptin antagonist (LA), and determined the influence of LA on the activities of leptin signaling molecules and the expressions of secretases associated with the production of Aβ 1-42. The finding showed that, accompanied with the inhibition on the level of Aβ 1-42 in primary neurons and APP/PS1 transgenic mice, geniposide induced the phosphorylation of JAK2 and STAT3, regulated the expression level of α- and β-secretase, and all of these could be prevented by the pre-incubation with LA. The results of this study suggest that geniposide may regulate the production of Aβ 1-42 via leptin signaling.
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In APP/PS1 mice, geniposide's inhibitory effect on Tau hyperphosphorylation and Aβ1-42 production is due to increased leptin signaling.
“Other studies performed in APP/PS1 have suggested that the inhibitory effect of geniposide on Tau hyperphosphorylation and Aβ1-42 production is due to an increase of leptin signaling (Liu et al., 2015; Liu et al., 2017)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Liu et al., 2017
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- Authors
- Liu, Z., Zhang, Y., Liu, J., & Yin, F.
- Affiliations
- Chongqing University of Technology (CN)
- Corresponding author
- Liu, Jianhui
- Yin, Fei
- Venue
- Archives of Pharmacal Research
- Published
- 2017-02-03
- Volume
- 40
- Issue
- 5
- Pages
- 571-578
- ISSN
- 0253-6269 (ISSN-L)
- 1976-3786
- OpenAlex
- W2583139546
- Cited by
- 21
- References
- 40
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Pharmacal Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (CN) (81173063)
- Chongqing Science Found for Distinguished Young Scholars (2014jcyjjq10003)
- the Innovative Research Team Development Program at the University of Chongqing (CXTDX201601031)
- The Innovation of Science and Technology Leading Talent in Chongqing (2014kjcxljrc18)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- geniposide, amyloid-beta 42, leptin signaling, Alzheimer's disease, APP/PS1 mice, JAK2/STAT3 signaling, secretases, alpha-secretase, beta-secretase, leptin antagonist, primary neurons, neuroprotection
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Peptide Fragments, Structure-Activity Relationship, Signal Transduction, Amyloid beta-Peptides, Leptin, Gardenia, Iridoids, Mice
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