Andrographolide attenuates microglia-mediated Aβ neurotoxicity partially through inhibiting NF-κB and JNK MAPK signaling pathway
- 18 July 2017
- journal article
- research article
- Published by Taylor & Francis Ltd in Immunopharmacology and Immunotoxicology
- Vol. 39 (5), 276-284
- https://doi.org/10.1080/08923973.2017.1344989
Abstract
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, β-amyloid (Aβ) peptides have been considered as a potent activator of neuroinflammation, the effect of ANDRO on Aβ-induced neuroinflammation has not been examined. In this study, we investigated the effects of ANDRO on Aβ(1–42)-induced neuroinflammation. We found that ANDRO significantly protected neuronal cells against microglia-mediated Aβ(1–42) toxicity and attenuated the release of preinflammatory productions such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nitric oxide (NO), and prostaglandin E2 (PGE2). 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-κB (NF-κB) by affecting IκB phosphorylation, and attenuated Aβ(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 Aβ(1–42), suggesting ANDRO may be an effective agent in modulating neuroinflammatory process in AD.Keywords
Funding Information
- Shanghai Jiaotong University Affiliated Xinhua Hospital research foundation (13YJ18)
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