Narirutin attenuates LPS-induced neuroinflammatory responses in both microglial cells and wild-type mice

Abstract

Background: Microglia-induced neuroinflammation plays a key role in the etiology and progression of neurodegenerative diseases. Narirutin, a flavanone glycoside naturally present in citrus fruits, demonstrates anti-oxidant and anti-inflammatory properties. This study aimed to investigate the effects and underlying mechanisms of narirutin in inhibiting microglia-mediated neuroinflammation.

Methods: The neuroprotective and anti-neuroinflammatory properties of narirutin were evaluated using both lipopolysaccharide (LPS)-stimulated BV-2 cells and mouse models. Real-time quantitative PCR, western blot analysis (WB), enzyme-linked immunosorbent assay, immunofluorescence staining, and flow cytometry were performed to assess the effects of narirutin on LPS-induced neuroinflammation. Transcriptomic analysis was conducted to identify narirutin-regulated differentially expressed genes in LPS-activated BV-2 cells. In addition, behavioral assessments comprising the open field test, forced swim test, and tail suspension test were performed to evaluate the impact of narirutin on LPS-induced sickness behavior. Neuroinflammation was assessed using WB and immunohistochemistry. Oxidative stress levels were quantified by measuring superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration.

Results: Narirutin demonstrated dose-dependent inhibition of LPS-induced pro-inflammatory cytokine production. This anti-inflammatory effect was mediated through suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Behavioral assessments revealed that narirutin administration significantly ameliorated LPS-induced sickness behaviors in the mouse model. Furthermore, narirutin administration suppressed microglial activation, enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels in the brain tissues of treated mice.

Conclusion: Our results demonstrate that narirutin significantly downregulates LPS-induced neuroinflammatory responses both in vitro and in vivo, suggesting its potential as a therapeutic agent for neuroinflammatory disorders.

Keywords: Lipopolysaccharide; Microglia; Narirutin; Neuroinflammation.