JLX001 Modulated the Inflammatory Reaction and Oxidative Stress in pMCAO Rats via Inhibiting the TLR2/4-NF-κB Signaling Pathway.

Abstract

Inflammatory reactions and oxidative stress play critical roles in cerebral ischemic injuries. Microglia are activated after ischemic injury. Activated microglia produce neurotoxic proinflammatory factors and reactive oxygen species (ROS), which have been demonstrated closely related TLR2/4-NF-κB signal pathways. This study was to evaluate the effect of JLX001 against ischemic injury and investigate the mechanisms. The permanent middle cerebral artery occlusion (pMCAO) model was employed in rats. The neurobehavioral score, brain infarction rate, brain water content, pathological changes, immunohistochemical staining, biochemical index (T-AOC, SOD, and MDA), proinflammatory factors (IL-1β, TNF-α, and NO), expression of TLR2/4 and nuclear translocation of NF-κB p65 were determined. To explore probable underlying mechanism of the neuroprotective effect of JLX001, BV-2 cells were exposed to in oxygen-glucose deprivation (OGD) for 4 h to mimic ischemic injury in vitro. The result showed that JLX001 significantly decreased neurological deficit score, infarct size, and brain edema, attenuated pathological changes, inhibited the activation of microglia, improved the process of oxidative stress, reduced the release of proinflammatory cytokines and downregulated TLR2/4-NF-κB signal pathway. Moreover, OGD reduced BV2 cell viability, induced oxidative damage, increased the release of proinflammatory factors and activated TLR2/4-NF-κB signal pathway, which was significantly reversed by the intervention of JLX001. This study demonstrates that JLX001 is effective in protecting the brain from ischemic injury, which may be mediated by regulating oxidative stress, inflammation and inhibiting TLR2/4-NFκB signal pathway.

• Authors: Yanying Qiu, Qiyang Yin, Yuxiang Fei, Yize Li, Hongfei Huang, Weirong Fang, Weiyang Shen, Bingwen Liang, Xiong Zhu, Yunman Li
• Journal: Neurochemical research (Neurochem Res) Vol. 44 Issue 8 Pg. 1924-1938 (Aug 2019) ISSN: 1573-6903 [Electronic] United States
• PMID: 31203481 (Publication Type: Journal Article)

Chemical References

• JLX001
• NF-kappa B
• Neuroprotective Agents
• Tlr2 protein, rat
• Tlr4 protein, rat
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Triterpenes

Topics

• Animals
• Cell Hypoxia (physiology)
• Cell Line
• Dentate Gyrus (pathology)
• Infarction, Middle Cerebral Artery (metabolism)
• Inflammation (metabolism)
• Male
• Mice
• NF-kappa B (metabolism)
• Neuroprotective Agents (therapeutic use)
• Oxidative Stress (drug effects)
• Rats, Sprague-Dawley
• Signal Transduction
• Toll-Like Receptor 2 (metabolism)
• Toll-Like Receptor 4 (metabolism)
• Triterpenes (therapeutic use)