Oxyimperatorin attenuates LPS-induced microglial activation in vitro and in vivo via suppressing NF-κB p65 signaling

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-kappa B p65 phosphorylation and nuclear translocation. However, OIMP did not affect LPSinduced I kappa B 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 proinflammatory mediators and cytokines via inhibition of NF-kappa B p65 signaling.