Alleviation of Depression-Like Symptoms Through Orientin-Mediated Regulation of Neuroinflammation and PI3K/AKT Signaling

Le résumé fourni par la source

Neuroinflammation is vital in depression's onset and development, making its relief a key treatment goal. Orientin (ORI), a natural flavonoid, is known to modulate inflammation, but whether it can ease depression by regulating neuro-inflammation remains uncertain. This study aimed to uncover ORI's antineuroinflammation mechanisms for treating depression. It utilized LPS-induced cell and mouse models and Chronic Unpredictable Mild Stress (CUMS) model. Enzyme-linked immunoassay, Western blotting, and immunofluorescence staining gauged ORI's anti-inflammatory effects. Behavioral tests assessed the impact on depressive symptoms. Network pharmacology and molecular biology methods probed its action mechanism and anti-inflammation targets. ORI effectively curbed inflammation, blocked M1 polarization, and reduced the inflammatory mediator release in LPS-induced BV2 cells and mice. In LPS-induced and CUMS depression mouse models, ORI notably alleviated depression-like behavior and neuroinflammation in the prefrontal cortex (PFC). Also, ORI treatment reduced the LPS-induced spike in the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in PFC neurons. The PI3K/AKT signaling pathway was found to underpin ORI's effects. Overall, ORI shows potential as a natural remedy for depression, influencing neuroinflammation and regulating microglial polarization and neuronal excitability to improve symptoms.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.