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Avarol protects HT22 neuronal cells from BV2 microglia cell-derived neuroinflammation in lipopolysaccharide-induction
Ji-Yeon Gu1, Ji-Yun Kang1, Won-Yung Lee2
1Institute of Bioscience & Integrative Medicine, Dunsan Hospital of Daejeon University, Daejeon, South Korea.
Background:
Pathological neuroinflammation is a critical factor that disrupts neuronal activity and, when sustained, ultimately contributes to neuronal death. Among the primary mediators of neuroinflammation, microglia play a central role in modulating brain immunity. However, their overactivation is closely associated with neuronal damage and structural remodeling of brain tissue, leading to the onset and progression of various neurodegenerative diseases.
Materials And Methods:
We investigated the neuroprotective effects of avarol, a marine-derived sesquiterpenoid, focusing on its ability to inhibit lipopolysaccharide (LPS)-induced overactivation of BV2 microglial cells and its subsequent impact on neuronal activity in HT-22 hippocampal neuronal cells.
Results:
Pretreatment with avarol significantly attenuated the LPS-induced release of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as well as oxidative stress markers such as reactive oxygen species (ROS) and nitric oxide (NO). These inhibitory effects were further substantiated by a dose-dependent reduction in nuclear translocation of nuclear factor-kappa B (NF-κB), a key transcription factor involved in the inflammatory signaling cascade. Regarding the interaction between microglia and neurons, both conditioned medium and co-culture systems demonstrated that avarol significantly attenuated alterations in neuronal plasticity-related molecules-such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)-induced by activated microglia.
Conclusions:
Overall, these findings suggest that avarol exerts neuroprotective effects through the modulation of microglia-mediated neuroinflammation. Importantly, avarol's capacity to traverse the blood-brain barrier highlights its potential as an effective pharmacological agent in mitigating neuroinflammation-associated neurological disorders.
Insights
Avarol, a marine compound, protects neurons by reducing microglial overactivation and inflammation. It crosses the blood-brain barrier, offering potential for treating neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Pathological neuroinflammation, driven by microglia, disrupts neuronal function and causes cell death.
- Microglial overactivation is linked to neuronal damage and neurodegenerative diseases.
- Understanding neuroinflammation is key to developing treatments for neurological disorders.
Purpose of the Study:
- To investigate the neuroprotective effects of avarol, a marine-derived sesquiterpenoid.
- To assess avarol's ability to inhibit lipopolysaccharide (LPS)-induced microglial activation.
- To evaluate avarol's impact on neuronal activity in the presence of activated microglia.
Main Methods:
- Utilized BV2 microglial cells and HT-22 hippocampal neuronal cells.
- Administered avarol pretreatment to inhibit LPS-induced microglial activation.
- Measured pro-inflammatory cytokines (TNF-α, IL-6), oxidative stress markers (ROS, NO), and NF-κB translocation.
- Assessed alterations in neuronal plasticity molecules (NGF, BDNF) using conditioned medium and co-culture systems.
Main Results:
- Avarol significantly reduced LPS-induced release of TNF-α and IL-6.
- Avarol attenuated oxidative stress markers, including ROS and NO.
- Dose-dependent inhibition of NF-κB nuclear translocation was observed with avarol.
- Avarol mitigated microglial-induced alterations in neuronal plasticity molecules like NGF and BDNF.
Conclusions:
- Avarol demonstrates neuroprotective effects by modulating microglia-mediated neuroinflammation.
- Avarol's ability to cross the blood-brain barrier suggests therapeutic potential.
- Avarol may be a promising agent for neurological disorders associated with neuroinflammation.
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