Oxyimperatorin attenuates LPS-induced microglial activation in vitro and in vivo via suppressing NF-κB p65 signaling - 22/03/24
, Cheong-Meng Chong a, ⁎ Abstract |
Background |
Microglia-mediated neuroinflammation is an important pathological feature in many neurological diseases; thus, suppressing microglial activation is considered a possible therapeutic strategy for reducing neuronal damage. Oxyimperatorin (OIMP) is a member of furanocoumarin, isolated from the medicinal herb Glehnia littoralis. However, it is unknown whether OIMP can suppress the neuroinflammation.
Purpose |
To investigate the neuroprotective activity of oxyimperatorin (OIMP) in LPS-induced neuroinflammation in vitro and in vivo models.
Methods |
In vitro inflammation-related assays were performed with OIMP in LPS-induced BV-2 microglia. In addition, intraperitoneal injection of LPS-induced microglial activation in the mouse brain was used to validate the anti-neuroinflammatory activity of OIMP.
Results |
OIMP was found to suppress LPS-induced neuroinflammation in vitro and in vivo. OIMP significantly attenuated LPS-induced the production of free radicals, inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines in BV-2 microglia without causing cytotoxicity. In addition, OIMP could reduce the M1 pro-inflammatory transition in LPS-stimulated BV-2 microglia. The mechanistic study revealed that OIMP inhibited LPS-induced NF-κB p65 phosphorylation and nuclear translocation. However, OIMP did not affect LPS-induced IκB phosphorylation and degradation. In addition, OIMP also was able to reduce LPS-induced microglial activation in mice brain.
Conclusion |
Our findings suggest that OIMP suppresses microglia activation and attenuates the production of pro-inflammatory mediators and cytokines via inhibition of NF-κB p65 signaling.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Oxyimperatorin suppresses LPA-induced inflammatory cytokines expression in BV2 microglia. |
• | Oxyimperatorin decreases the activation of pro-inflammatory microglia. |
• | Oxyimperatorin inhibits NF-κB signaling pathways in LPS-induced microglia. |
• | Oxyimperatorin reduces LPS-induced neuroinflammation in mice hippocampus. |
Keywords : Microglia, Neuroinflammation, Oxyimperatorin, Pro-inflammatory cytokines, NF-κB p65
Abbreviations : BBB, CCK8, CNS, COX-2, DMSO, DPPH, ELISA, FRAP, GESA, Iba1, IKK, IL-6, iNOS, KEGG, LPS, MAPKs, NF-κB, NO, NOD, OIMP, PBS, PFA, ROS, TLR4, TNF-α
Plan
Vol 173
Article 116379- avril 2024 Retour au numéro
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