The phytochemical agathisflavone modulates miR146a and miR155 in activated microglia involving STAT3 signaling

Balbino Lino dos Santos, Cleonice Creusa dos Santos, Karina Costa da Silva, Carolina Kymie Vasques Nonaka, Bruno Solano de Freitas Souza, Jorge Mauricio David, Juciele Valéria Ribeiro de Oliveira, Maria de Fátima Dias Costa, Arthur Morgan Butt, Victor Diogenes Amaral da Silva, Silvia Lima Costa

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs (miRs) act as important post-transcriptional regulators of gene expression in glial cells and have been shown to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). Here, we investigated the effects of agathisflavone, a biflavonoid purified from the leaves of Cenostigma pyramidale (Tul.), on modulating the expression of miRs and inflammatory mediators in activated microglia. C20 human microglia were exposed to oligomers of the β-amyloid peptide (Aβ, 500 nM) for 4 h or to lipopolysaccharide (LPS, 1 µg/mL) for 24 h and then treated or not with agathisflavone (1 µM) for 24 h. We observed that β-amyloid and LPS activated microglia to an inflammatory state, with increased expression of miR-146a, miR-155, IL1-β, IL-6, and NOS2. Treatment with agathisflavone resulted in a significant reduction in miR146a and miR-155 induced by LPS or Aβ, as well as inflammatory cytokines IL1-β, IL-6, and NOS2. In cells stimulated with Aβ, there was an increase in p-STAT3 expression that was reduced by agathisflavone treatment. These data identify a role for miRs in the anti-inflammatory effect of agathisflavone on microglia in models of neuroinflammation and AD.
Original languageEnglish
Article number2547
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume25
Issue number5
DOIs
Publication statusPublished - 22 Feb 2024

Keywords

  • agathisflavone
  • human microglia
  • anti-inflammatory
  • miRNAs
  • STAT3

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