Research Paper Volume 13, Issue 20 pp 23780—23795
Matairesinol exerts anti-inflammatory and antioxidant effects in sepsis-mediated brain injury by repressing the MAPK and NF-κB pathways through up-regulating AMPK
- 1 Rehabilitation Medicine Department, Shanxi Provincial People’s Hospital, Taiyuan 030001, Shanxi, China
Received: July 21, 2021 Accepted: September 28, 2021 Published: October 27, 2021https://doi.org/10.18632/aging.203649
How to Cite
Copyright: © 2021 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Brain injury is a familiar complication of severe sepsis, in which excessive inflammation and oxidative stress are the main mechanisms leading to acute brain injury. Here, we focus on probing the function and mechanism of Matairesinol (Mat) in sepsis-mediated brain injury. We established a rat sepsis model by cecal ligation and perforation (CLP) and constructed an in vitro sepsis model by treating neurons and microglia with lipopolysaccharide (LPS). Rats and cells were treated with varying concentrations of Mat, and the changes of neural function, neuronal apoptosis, microglial activation, neuroinflammation and the expression of oxidative stress factors in brain tissues were examined. Additionally, the activation of the MAPK, NF-κB and AMPK pathways in brain tissues and cells was evaluated by Western blot (WB) and/or immunohistochemistry (IHC). Our findings illustrated that Mat improved neuronal apoptosis and weakened microglial activation in CLP rats. Meanwhile, Mat hampered the expression of pro-inflammatory factors (TNF-α, IL-1β, IL-6, IFN-γ, IL-8, and MCP1) and facilitated the contents of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in brain tissues and microglia. Mechanistically, Mat concentration-dependently dampened the phosphorylation of MAPK, JNK and NF-κB in CLP rats and LPS-stimulated microglia and up-regulated Nrf2 and HO-1. Besides, Mat facilitated the AMPK expression. Meanwhile, Compound C, a specific inhibitor of the AMPK pathway, substantially reduced the neuronal protection and anti-inflammatory effects mediated by Mat. Overall, Mat exerts anti-inflammatory and anti-oxidative stress effects by up-regulating AMPK, thereby ameliorating sepsis-mediated brain injury.