科研之友
微信
新浪微博
Facebook
分享链接
摘要
Neuroinflammation plays a critical role in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD). Microglial cells after activated play critical roles in development of neuroinflammation, and may accelerate the progression of AD. Andrographolide (ANDRO), a potent naturally extracted substance, has been demonstrated to exert suppressive effects on LPS-induced inflammation by modulating macrophage and microglia overactivation. Whereas in AD, beta-amyloid (A beta) peptides have been considered as a potent activator of neuroinflammation, the effect of ANDRO on A-induced neuroinflammation has not been examined. In this study, we investigated the effects of ANDRO on A beta(1-42)-induced neuroinflammation. We found that ANDRO significantly protected neuronal cells against microglia-mediated A beta(1-42) toxicity and attenuated the release of preinflammatory productions such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), nitric oxide (NO), and prostaglandin E-2 (PGE(2)). It also downregulated the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in microglial cells. Further the involved mechanism study demonstrated that ANDRO inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B) by affecting I kappa B phosphorylation, and attenuated A beta(1-42)-induced JNK-MAPK overactivation. In summary, this study, for the first time, revealed ANDRO reduced inflammation-mediated neuronal damage by blocking inflammatory responses of microglial cells to A beta(1-42), suggesting ANDRO may be an effective agent in modulating neuroinflammatory process in AD.
