Oxyresveratrol attenuates LPS-induced oxidative stress and neuroinflammation through inhibiting PI3K/Akt/NF-κB signaling pathway in mice

Abstract Background: Oxyresveratrol (OXY), a polyphenolic compound derived from several plants, has been reported to have anti-oxidative and anti-inflammatory activities. However, the effect and mechanism of OXY in regulating neuroinflammation in vivo is still unclear. Thus, this research focused on the anti-neuroinflammatory effects and mechanism in mice.Methods: A BV-2 cell line and C57BL/6 mice were used to establish LPS-induced neuroinflammation models in vitro and in vivo, respectively. C57BL/6 mice were exposed to LPS (250 μg/kg), OXY (50, 100 mg/kg), resveratrol (100 mg/kg), TPP488 (5 mg/kg). After modeling, behavioral test was established and the molecular mechanism was further analyzed.Results: The pathways enrichment analysis results of the 69 common targets show that the PI3K-Akt pathway and the NF-κB pathway may be the related mechanisms of oxyresveratrol in regulating neuroinflammation. In vitro, OXY at a concentration of 25 μM can significantly inhibit the expression of NO induced by LPS. In vivo, OXY significantly improved cognition impairment and alleviated the neuronal apoptosis caused by LPS. The protective effect of OXY on neuroinflammation is mainly through inhibiting the phosphorylation process of the PI3K/Akt/NF-κB pathway to downregulate the expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, Inducible Nitric Oxide Synthase (iNOS), Cyclooxygenase-2 (COX2), Matrix metalloproteinase 9 (MMP9). The oxidative stress and the excessive activation of microglia and astrocytes was suppressed in the brain to alleviate neuroinflammation.Discussion: The research first revealed that OXY can alleviate LPS-induced oxidative stress and neuroinflammation in mice by regulating PI3K/Akt/NF-κB signaling pathway.