TY - JOUR
T1 - The phytochemical agathisflavone modulates miR146a and miR155 in activated microglia involving STAT3 signaling
AU - dos Santos, Balbino Lino
AU - dos Santos, Cleonice Creusa
AU - da Silva, Karina Costa
AU - Nonaka, Carolina Kymie Vasques
AU - Souza, Bruno Solano de Freitas
AU - David, Jorge Mauricio
AU - de Oliveira, Juciele Valéria Ribeiro
AU - Costa, Maria de Fátima Dias
AU - Butt, Arthur Morgan
AU - da Silva, Victor Diogenes Amaral
AU - Costa, Silvia Lima
PY - 2024/2/22
Y1 - 2024/2/22
N2 - 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.
AB - 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.
KW - agathisflavone
KW - human microglia
KW - anti-inflammatory
KW - miRNAs
KW - STAT3
U2 - 10.3390/ijms25052547
DO - 10.3390/ijms25052547
M3 - Article
SN - 1422-0067
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 5
M1 - 2547
ER -