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3',4',7-Trihydroxyflavone Downregulates NO Production in LPS- or IFN-γ-Activated MG6 Microglial Cells by Attenuating

Tatsuhiro Akaishi1, Shohei Yamamoto1, Kazuho Abe1

  • 1Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University.

Biological & Pharmaceutical Bulletin
|March 1, 2022
PubMed

Insights

3

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglial activation drives neuroinflammation in neurodegenerative diseases like Alzheimer's.
  • 3',4',7-trihydroxyflavone shows neuroprotective potential against oxidative stress and amyloid-beta aggregation.
  • Its impact on microglial activation remains largely unexplored.

Purpose of the Study:

  • To investigate the anti-neuroinflammatory effects of 3',4',7-trihydroxyflavone on activated microglia.
  • To elucidate the underlying molecular mechanisms, focusing on signaling pathways.

Main Methods:

  • MG6 microglial cells were stimulated with lipopolysaccharide (LPS) or interferon-gamma (IFN-γ).
  • The effects of 3',4',7-trihydroxyflavone on nitric oxide (NO) generation, inducible NO synthase (iNOS) expression, and key signaling pathways (JNK, STAT1) were assessed.
  • Pharmacological inhibition of the JNK pathway was used for validation.

Main Results:

  • 3',4',7-trihydroxyflavone significantly inhibited LPS/IFN-γ-induced NO generation and iNOS upregulation.
  • It suppressed the phosphorylation of signal transducer and activator of transcription 1 (STAT1).
  • The compound specifically inhibited LPS-induced c-Jun N-terminal kinase (JNK) phosphorylation, but not ERK or p38 MAPK. Inhibition of JNK mimicked the anti-inflammatory effects.

Conclusions:

  • 3',4',7-trihydroxyflavone demonstrates significant anti-neuroinflammatory properties in microglia.
  • Its mechanism involves the inhibition of the JNK-STAT1 signaling pathway.
  • This flavonoid represents a potential therapeutic agent for neuroinflammatory conditions.
Keywords:
3′,4′,7-trihydroxyflavoneanti-neuroinflammatory effectc-Jun N-terminal kinasemicrogliasignal transducer and activator of transcription 1

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