Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Neuroinflammation, driven by microglia activation, is implicated in neurological disorders.
• Hesperetin, a flavanone from citrus fruits, shows anti-inflammatory properties.
• The anti-neuroinflammatory effects of hesperetin on microglia remain largely unexplored.

Purpose of the Study:

• To investigate the potential anti-neuroinflammatory effects of hesperetin.
• To examine hesperetin's impact on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells.
• To assess hesperetin's influence on inflammatory mediators and signaling pathways in the brain.

Main Methods:

• Utilized LPS-stimulated BV-2 microglial cells to model neuroinflammation.
• Quantified nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression.
• Measured the secretion levels of key inflammatory cytokines, including IL-1β and IL-6.
• Analyzed the phosphorylation status of ERK1/2 and p38 MAPK signaling pathways.
• Assessed microglia and astrocyte activation in LPS-challenged mouse brains.

Main Results:

• Hesperetin significantly inhibited nitric oxide production and inducible nitric oxide synthase expression in LPS-stimulated BV-2 cells.
• Hesperetin markedly reduced the secretion of pro-inflammatory cytokines, IL-1β and IL-6.
• Hesperetin suppressed the phosphorylation of ERK1/2 and p38 MAPK pathways.
• In vivo, hesperetin attenuated microglia and astrocyte activation in the mouse brain.

Conclusions:

• Hesperetin demonstrates significant anti-neuroinflammatory effects by modulating microglial activation and inflammatory responses.
• Hesperetin's mechanism involves the inhibition of NO, iNOS, pro-inflammatory cytokines, and MAPK signaling.
• These findings suggest hesperetin holds promise as a potential prophylactic agent for neurodegenerative diseases.