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. 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.

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Protein kinase B


Nuclear factor erythroid 2-related factor 2


Heme oxygenase-1


Nuclear transcription factor-κB


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This work was funded by National Natural Science Foundation of China (project No. 31772547, 31702211), Jilin Scientific and Technological Development Program (project No. 20170623083-04TC), and JLU Science and Technology Innovative Research Team (project No. 201910183X588, 201910183811).

Author information




TM, SF, DH, and GH performed most of the experiments, analyzed the results, and wrote the manuscript. DL conceived and designed this study and analyzed the data. They were involved in all aspects of the study read and modified the manuscript. XG, YZ, BH, JD, AZ, and YS also participated in the research. All the authors read and approved the final manuscript.

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Correspondence to Dianfeng Liu.

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Meng, T., Fu, S., He, D. et al. Evodiamine Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in BV-2 Cells via Regulating AKT/Nrf2-HO-1/NF-κB Signaling Axis. Cell Mol Neurobiol 41, 115–127 (2021). https://doi.org/10.1007/s10571-020-00839-w

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  • Evodiamine
  • Microglia
  • Neuroinflammation
  • Neurodegenerative disease