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The Phytochemical Agathisflavone Modulates miR146a and miR155 in Activated Microglia Involving STAT3 Signaling
Balbino Lino Dos Santos1,2, Cleonice Creusa Dos Santos1, Karina Costa da Silva1
1Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, BA, Brazil.
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.
Insights
Agathisflavone reduces microRNA (miR) and inflammatory mediator expression in activated microglia, offering potential for Alzheimer's disease (AD) and neuroinflammation treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- MicroRNAs (miRs) regulate gene expression in glial cells and are implicated in neurodegenerative diseases like Alzheimer's disease (AD).
- Activated microglia contribute to neuroinflammation, a key factor in AD pathogenesis.
Purpose of the Study:
- To investigate the anti-inflammatory effects of agathisflavone on microglial cells.
- To determine if agathisflavone modulates microRNA expression in activated microglia relevant to AD.
Main Methods:
- Human microglia (C20) were activated using amyloid-beta (Aβ) or lipopolysaccharide (LPS).
- Cells were treated with agathisflavone and expression levels of specific miRs (miR-146a, miR-155) and inflammatory mediators (IL1-β, IL-6, NOS2, p-STAT3) were analyzed.
Main Results:
- Aβ and LPS induced an inflammatory state in microglia, increasing miR-146a, miR-155, IL1-β, IL-6, and NOS2 expression.
- Agathisflavone treatment significantly reduced Aβ- or LPS-induced miR-146a and miR-155 expression.
- Agathisflavone also decreased the expression of inflammatory mediators IL1-β, IL-6, and NOS2, and reduced p-STAT3 levels in Aβ-stimulated cells.
Conclusions:
- Agathisflavone exhibits anti-inflammatory properties in microglia activated by Aβ and LPS.
- MicroRNAs play a role in the anti-inflammatory mechanism of agathisflavone in neuroinflammation and AD models.
