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Introduction
Alzheimer's disease (AD), which is the most common age-associated neurodegenerative disorder, causes progressive dementia, and microglia-mediated neuroinflammation is key in the pathogenesis of AD (1). Microglia are the resident immune cells of the brain, which are important in host defense and tissue repair in the central nervous system (2). In response to brain injury or immunological stimuli, including amyloid β (Aβ) or lipopolysaccharide (LPS), microglia are activated, producing various proinflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nitric oxide (NO), and reactive oxygen species (ROS) (3). Accumulation of these mediators contributes to neuronal damage and aggravates AD progression. Therefore, the production of inflammatory factors by microglia requires inhibition to prevent neuroinflammation and neurodegeneration in AD.
Resveratrol (3,4′,5-trihydroxy-trans-stilbene), which is a natural, nonflavonoid, polyphenolic compound, is present in several plant species, including giant knotweeds, peanuts, mulberries and grapes, and is found in red wine (4). Evidence suggests that resveratrol exerts neuroprotective effects against neurodegenerative diseases, due to its anti-inflammatory properties (5,6). In vitro studies have demonstrated that resveratrol inhibits the production of LPS-induced NO and TNF-α in murine microglial cells (7,8), as well as the production of prostaglandin E2 and free radicals in rat primary microglia (9). In addition, previous studies have demonstrated that resveratrol prevents microglial activation and subsequent inflammatory-mediator release by inhibiting transcriptional factors, including nuclear factor-κB (10,11). The neuroprotective effects of resveratrol have been detected in numerous studies; however, the mechanisms underlying its beneficial effects remain poorly understood.
NADPH oxidase has been confirmed as an important contributor to microglia-mediated neuroinflammation and neurodegeneration (12,13). Previous studies have demonstrated that soluble oligomeric (o)Aβ, which is present in the cortex of patients with AD, exhibits more marked correlation with AD symptoms, compared with fibrillar Aβ in amyloid plaques (14,15). Using the BV-2 murine microglial cell line, our previous study demonstrated that oAβ induced the activated properties of microglia, and activation was inhibited by the NADPH oxidase inhibitors, diphenyleneiodonium (DPI) and apocynin. These results suggested that NADPH oxidase may be involved in the activation of oAβ-induced microglia (16). The present study aimed to use BV-2 microglia cultures to investigate the inhibitory effects of resveratrol on the activation of oAβ-induced microglia and further investigate the role of NADPH oxidase.
Materials and methods
Regents
Dulbecco's...