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Effects of hypnotic bromovalerylurea on microglial BV2 cells
Shun Kawasaki1, Naoki Abe1, Fumito Ohtake2
1Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan; Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Journal of Pharmacological Sciences
|June 25, 2017
Summary
Bromovalerylurea (BU), an old sedative, exhibits anti-inflammatory properties by reducing nitric oxide and inflammatory cytokines. Its effects stem from inhibiting JAK1/STAT1 pathways and lowering cellular ATP levels.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Bromovalerylurea (BU), a sedative-hypnotic, demonstrates unexpected anti-inflammatory effects.
- Microglia play a crucial role in neuroinflammation, making them a target for therapeutic interventions.
Purpose of the Study:
- To elucidate the anti-inflammatory mechanisms of bromovalerylurea (BU) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.
- To investigate the roles of JAK1/STAT1 signaling and intracellular ATP levels in BU's anti-inflammatory actions.
Main Methods:
- BV2 cells were treated with LPS, BU, filgotinib (JAK1 inhibitor), or rotenone (mitochondrial complex I inhibitor).
- Nitric oxide (NO) release, pro-inflammatory cytokine expression, nuclear factor-κB (NF-κB) translocation, STAT1 phosphorylation, and intracellular ATP (iATP) levels were measured.
- Gene knockdown of JAK1, STAT1, and IRF1 was performed to assess their involvement.
Main Results:
- BU suppressed LPS-induced NO release and pro-inflammatory cytokine expression without affecting NF-κB.
- BU inhibited LPS-induced STAT1 phosphorylation and IRF1 expression, but JAK1 inhibition only partially reduced NO release.
- BU and rotenone similarly reduced iATP levels, and their combination with filgotinib synergistically suppressed NO release.
Conclusions:
- BU's anti-inflammatory effects are likely due to a synergistic action involving the inhibition of JAK1/STAT1-dependent pathways and a reduction in intracellular ATP levels.
- These findings suggest novel therapeutic potential for bromovalerylurea in inflammatory conditions.

