期刊
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
卷 17, 期 3, 页码 306-317出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10286020.2014.1003183
关键词
FLZ; Alzheimer's disease; beta-amyloid; neuroinflammation; lipopolysaccharide
资金
- Fundamental Research Funds for the Central Universities [2012S08]
- Beijing NOVA Program [2011109]
- PUMC Youth Fund [2012J19, 3332013111]
- Program for New Century Excellent Talents in University [3332013128]
Alzheimer's disease (AD) is the most common neurodegenerative disorder in which neuroinflammation plays an important role. FLZ is a novel synthetic derivative of natural squamosamide. Previous studies demonstrated that FLZ had neuroprotective effects on AD models and showed strong anti-inflammatory property in Parkinson's disease models. However, whether the neuroprotective effects of FLZ on AD are associated with its anti-inflammatory property is still not fully elucidated. In this study, we aimed to investigate the ability of FLZ in modulating inflammation. The results showed that FLZ significantly improved memory deficits and alleviated neuronal damage as well as neuronal loss in the hippocampus of mice intracerebroventricular injected with lipopolysaccharide (LPS). Mechanistic studies revealed that the neuroprotective effects of FLZ were due to the suppression of neuroinflammation induced by LPS, as indicated by inactivation of astrocytes and microglia, reduced production of tumor necrosis factor-alpha, interleukin-1 beta, and nitric oxide, as well as decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase. The beneficial effects of FLZ on AD were further supported by the finding that FLZ attenuated beta-amyloid production through inhibiting beta-amyloid precursor protein cleaving enzyme 1 expression. These results suggested that anti-inflammatory agent could be useful for the treatment of AD.
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