Nootkatone, a neuroprotective agent from Alpiniae Oxyphyllae Fructus, improves cognitive impairment in lipopolysaccharide-induced mouse model of Alzheimer's disease
Abstract
Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Our previous study demonstrated that petroleum ether extracts from Alpiniae Oxyphyllae Fructus(AOF) could attenuate lipopolysaccharide (LPS)-induced learning and memory impairment in mice, which could be associated with its inhibitory effect on neuroinflammation. Therefore, our present study is to investigate the potential therapeutic neuroprotective effects of nootkatone (NKT) on an AD mouse model induced by intracerebroventricular injection of LPS. We found that NKT (10 mg/kg) group showed good performance in behavior experiments including Y-maze test and Morris water maze test. The results of histopathological examination and immunohistochemical analysis showed that LPS induced degeneration of neurons and activation of microglia particularly in hippocampus and NKT (10 mg/kg) reversed these changes. Enzyme linked immunosorbent assay and western blot analysis also demonstrated that the model group had increased expression of IL-1β, IL-6, TNF-α, NLRP3 and NF-κB p65, especially in hippocampus relative to sham-operated group, and NKT (10 mg/kg) decreased the high expression of these inflammatory cytokines. Collectively, these data indicated that LPS-induced learning and memory impairments in mice could be improved by NKT, which was associated with attenuating neuroinflammatory responses. Our study indicated that NKT could act as a potential therapeutic agent for the treatment of neuroinflammation and AD.
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Nootkatone's improvement of LPS-induced memory/learning impairment is associated with attenuating neuroinflammatory activity through expression of transcription factor NF-κB-p65.
“which was proposed to be associated with its attenuating neuroinflammatory activity through the expression of transcription factor NF-κB-p65.”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [143]
Nootkatone at 10 mg/kg showed significant improvement in neuroprotective potential on evaluation through Morris water maze and Y maze.
“Nootkatone at 10 mg/kg showed significant improvement in neuroprotective potential on evaluation through various behavioral models (Morris water maze and Y maze).”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [143]
Nootkatone isolated from Alpiniae oxyphyllae Fructus improves lipopolysaccharide-induced memory and learning impairment.
“Wanga et al. [143] isolated the nootkatone from petroleum ether extract of Alpiniae oxyphyllae Fructus and demonstrated that it could improve the lipopolysaccharide-induced memory and learning impairment”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [143]
Ambrosin and nootkatone, as novel sesquiterpenes, could significantly reduce expression of transcription factor NF-κβp65 in experimental groups.
“Hence ambrosin and nootkatone, as novel sesquiterpenes, could significantly reduce the expression of this transcription factor (NF-κβp65) in experimental groups.”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [143]
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Self-citation
- Authors
- Wang, Y., Wang, M., Xu, M., Li, T., Fan, K., Yan, T., Xiao, F., Bi, K., & Jia, Y.
- Affiliations
- Shenyang Pharmaceutical University (CN)
- Corresponding author
- Jia, Ying
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 62
- Pages
- 77-85
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W2847678343
- Cited by
- 86
- References
- 47
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 12 · 2023: 17 · 2022: 14 · 2021: 9 · 2020: 11 · 2019: 13
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Guangxi University of Chinese Medicine (YJS201612)
- National Natural Science Foundation of China (81573580)
- Department of Education of Liaoning Province (17-137-1-00)
- 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
- nootkatone, Alzheimer's disease, neuroprotection, neuroinflammation, lipopolysaccharide, learning and memory impairment, hippocampus, microglial activation, neurodegeneration, inflammatory cytokines, NLRP3 inflammasome, NF-κB, intracerebroventricular administration
- MeSH terms
- Polycyclic Sesquiterpenes, Alzheimer Disease, Animals, Behavior, Animal, Brain, Disease Models, Animal, Lipopolysaccharides, Male, Mice, Inbred C57BL, Motor Activity, Sesquiterpenes, Cytokines, Neuroprotective Agents, Maze Learning, Alpinia, Cognitive Dysfunction
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