ReferenceID 1733
Daphnetin ameliorates Aβ pathogenesis via STAT3/GFAP signaling in an APP/PS1 double-transgenic mouse model of Alzheimer's disease
Pharmacol Res
Alzheimer's disease (AD) has become a major public health problem that affects the elderly population. Therapeutic compounds with curative effects are not available due to the complex pathogenesis of AD. Daphnetin, a nat
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- Reference Id
- 1733
- Evidence Id
- 18323
- Core Evidence Id
- 18323
- Source Reference Id
- 3445
- Herb2 Reference Id
- HBREF004242
- Subject Paper Key
- HBIN022677_35452800
- Pubmed Id
- 35452800
- Doi
- 10.1016/j.phrs.2022.106227
- Paper Title
- Daphnetin ameliorates Aβ pathogenesis via STAT3/GFAP signaling in an APP/PS1 double-transgenic mouse model of Alzheimer's disease
- Paper Abstract
- Alzheimer's disease (AD) has become a major public health problem that affects the elderly population. Therapeutic compounds with curative effects are not available due to the complex pathogenesis of AD. Daphnetin, a natural coumarin derivative and inhibitor of various kinases, has anti-inflammatory and antioxidant activities. In this study, we found that daphnetin improved spatial learning and memory in an amyloid precursor protein (APP)/presenilin 1 (PS1) double-transgenic mouse model of AD. Daphnetin markedly decreased the levels of amyloid-β peptide 1-40 (Aβ 40 ) and 1-42 (Aβ 42 ) in the cerebral cortex, downregulated the expressions of enzymes involved in APP processing, e.g., beta-site APP-cleaving enzyme (BACE), nicastrin and presenilin enhancer protein 2 (PEN2). We further found the reduced serum levels of inflammatory factors, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and chemokine (C-C motif) ligand 3 (CCL3), while daphnetin increased total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) levels in the serum. Interestingly, daphnetin markedly decreased the expression of glial fibrillary acidic protein (GFAP) and the upstream regulatory molecule- phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in APP/PS1 mice, and mainly inhibited the phosphorylation of STAT3 at Ser727 to decrease GFAP expression evidenced in a LPS-activated glial cell model. These results suggest that daphnetin ameliorates cognitive deficits and that Aβ deposition in APP/PS1 mice is mainly correlated with astrocyte activation and APP processing.
- Journal
- Pharmacol Res
- Publish Year
- 2022
- Experiment Subject
- mouse; lps-activated glial cell model
- Experiment Type
- Animal Experiment
- Phenotype Related
- Cognitive Deficits; Tumor; Alzheimer's Disease
- Paper Title Cn
- Paper Title En
- Daphnetin ameliorates Aβ pathogenesis via STAT3/GFAP signaling in an APP/PS1 double-transgenic mouse model of Alzheimer's disease
- Bilingual Status
- semi_complete