Journal
MOLECULES
Volume 28, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/molecules28052406
Keywords
LPS; neuroinflammation; microglia; Ergosterol; NF-kappa B
Ask authors/readers for more resources
In this study, we identified Ergosterol as an effective anti-neuroinflammatory agent that inhibits the NF-kappa B pathway induced by LPS in microglia cells. We found that Ergosterol can significantly decrease the pro-inflammatory cytokines induced by LPS, possibly by inhibiting the NF-kappa B, AKT, and MAPK signaling pathways. Moreover, Ergosterol treatment in mice reduced microglial activation and pro-inflammatory cytokine levels, and restored synaptic protein expression, thereby reducing neuron damage.
Inflammation caused by microglial activation is important in neurodegenerative diseases. In this research, we tried to identify safe and effective anti-neuroinflammatory agents by screening a natural compounds library and found that Ergosterol can inhibit the nuclear factor kappa-light-chain enhancer of the activated B cells (NF-kappa B) pathway induced by lipopolysaccharide (LPS) in microglia cells. Ergosterol has been reported to be an effective anti-inflammatory agent. Nevertheless, the potential regulatory role of Ergosterol in neuroinflammatory responses has not been fully investigated. We further investigated the mechanism of Ergosterol that regulates LPS-induced microglial activation and neuroinflammatory reactions both in vitro and in vivo. The results showed that Ergosterol can significantly decrease the pro-inflammatory cytokines induced by LPS in BV2 and HMC3 microglial cells, possibly by inhibiting the NF-kappa B, protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, we treated Institute of Cancer Research (ICR) mice with a safe concentration of Ergosterol following LPS injection. Ergosterol treatment significantly decreased microglial activation-associated ionized calcium-binding adapter molecule-1 (IBA-1), NF-kappa B phosphorylation, and pro-inflammatory cytokine levels. Moreover, Ergosterol pretreatment clearly reduced LPS-induced neuron damage by restoring the expression of synaptic proteins. Our data may provide insight into possible therapeutic strategies for neuroinflammatory disorders.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available