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Luteolin alleviates cognitive impairment in Alzheimer’s disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation
- Source :
- Acta Pharmacol Sin
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer’s disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg(−1) · d(−1), ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1β, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.
- Subjects :
- Mice, Transgenic
Protein Serine-Threonine Kinases
Pharmacology
Neuroprotection
Article
Proinflammatory cytokine
Mice
chemistry.chemical_compound
Alzheimer Disease
Endoribonucleases
medicine
Animals
Cognitive Dysfunction
Pharmacology (medical)
Luteolin
Neuroinflammation
business.industry
Cell growth
Endoplasmic reticulum
General Medicine
Endoplasmic Reticulum Stress
Rats
Disease Models, Animal
medicine.anatomical_structure
chemistry
Neuroinflammatory Diseases
Unfolded protein response
business
Astrocyte
Subjects
Details
- ISSN :
- 17457254 and 16714083
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Acta Pharmacologica Sinica
- Accession number :
- edsair.doi.dedup.....85a98363e9e305df61558adc175d1dee