Evodiamine Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in BV-2 Cells via Regulating AKT/Nrf2-HO-1/NF-κB Signaling Axis

Neuroinflammation is caused by excessive activation of microglia and plays an essential role in neurodegenerative diseases. After activation, microglia produce several kinds of inflammatory mediators, trigger an excessive inflammatory response, and ultimately destroy the surrounding neurons. Therefo...

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Published in:Cellular and molecular neurobiology 2021, Vol.41 (1), p.115-127
Main Authors: Meng, Tianyu, Fu, Shoupeng, He, Dewei, Hu, Guiqiu, Gao, Xiyu, Zhang, Yufei, Huang, Bingxu, Du, Jian, Zhou, Ang, Su, Yingchun, Liu, Dianfeng
Format: Article
Language:English
Subjects:
AKT protein
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cyclooxygenase-2
Dopamine receptors
Drug development
Inflammation
Interleukin 6
Lipopolysaccharides
Microglia
Neurobiology
Neurodegenerative diseases
Neuronal-glial interactions
Neurosciences
NF-κB protein
Nitric oxide
Nitric-oxide synthase
Original Research
Phosphorylation
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary:Neuroinflammation is caused by excessive activation of microglia and plays an essential role in neurodegenerative diseases. After activation, microglia produce several kinds of inflammatory mediators, trigger an excessive inflammatory response, and ultimately destroy the surrounding neurons. Therefore, agents that inhibit neuroinflammation may be potential drug candidates for neurodegenerative diseases. Evodiamine (EV) has anti-inflammatory functions in peripheral tissues. However, whether EV exerts the same function in neuroinflammation is not known. In the present study, the aim was to explore whether EV attenuates microglial overactivation and therefore suppresses the development of neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. It was found that EV effectively inhibited expression of proinflammatory mediators (cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) via AKT/Nrf2/HO-1 activation and suppressed NF-κB p65 phosphorylation. In addition, EV could suppress LPS-induced inflammatory response and loss of dopaminergic neuron in mouse mesencephalic neuron--glia cells. Hence, these findings demonstrate that EV suppresses neuroinflammation caused by overactivated microglia via regulating the AKT/Nrf2/HO-1/NF-κB signaling axis.
ISSN:0272-4340
1573-6830
DOI:10.1007/s10571-020-00839-w