The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination

Almeida, Monique Marylin Alves de; Pieropan, Francesca; Oliveira, Larissa de Mattos; Santos, Manoelito Coelho dos; David, Jorge; David, Juceni P.; Silva, Victor Diógenes A. da; Souza, Catiane; Costa, Sílvia Lima; Butt, Arthur M.

doi:10.1016/j.phrs.2020.104997

Cited by 21 publications

(21 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a cuprizone mouse model, the levels of iNOS, TNF-α, and TSPO, which are expressed in pro-inflammatory microglia/macrophages, increase by weeks 5–6 of cuprizone treatment, whereas the levels of CD206, CD163, and Arg1, which are expressed in alternate microglia/macrophages, do not significantly change during or after cuprizone treatment ( Abdi et al, 2021 ; Klein et al., 2018 ). We therefore focused our analysis on CD16/32, which is expressed in pro-inflammatory microglia and macrophages ( de Almeida et al., 2020 ; Miron et al., 2013 ).…”

Section: Resultsmentioning

confidence: 99%

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

et al. 2023

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

et al. 2023

View full text Add to dashboard Cite

“…Flavonoid-rich ethanol extract from the leaves of Diospyros kaki can alleviate microglia and astrocyte activation, inhibit neuroinflammation, and attenuate neuronal apoptosis and synaptic dysfunction in D-galactose-aged mice [ 22 ]. Flavonoid-agathisflavone derived from the Brazilian plant Poincianella pyramidalis is able to regulate microglia polarization and promote remyelination [ 23 ]. To the best of our knowledge, this is the first report demonstrating that isoschaftoside is capable of regulating neuroinflammation in BV2 microglia.…”

Section: Discussionmentioning

confidence: 99%

Isoschaftoside Inhibits Lipopolysaccharide-Induced Inflammation in Microglia through Regulation of HIF-1α-Mediated Metabolic Reprogramming

Guan

Sun

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Isoschaftoside is a C-glycosyl flavonoid extracted from the root exudates of Desmodium uncinatum and Abrus cantoniensis. Previous studies suggested that C-glycosyl flavonoid has neuroprotective effects with the property of reducing oxidative stress and inflammatory markers. Microglia are key cellular mediators of neuroinflammation in the central nervous system. The aim of this study was to investigate the effect of isoschaftoside on lipopolysaccharide-induced activation of BV-2 microglial cells. The BV-2 cells were exposed to 10 ng/ml lipopolysaccharide and isoschaftoside (0–1000 μM). Isoschaftoside effectively inhibited lipopolysaccharide-induced nitric oxide production and proinflammatory cytokines including iNOS, TNF-α, IL-1β, and COX2 expression. Isoschaftoside also significantly reduced lipopolysaccharide-induced HIF-1α, HK2, and PFKFB3 protein expression. Induction of HIF-1α accumulation by CoCl2 was inhibited by isoschaftoside, while the HIF-1α specific inhibitor Kc7f2 mitigated the metabolic reprogramming and anti-inflammatory effect of isoschaftoside. Furthermore, isoschaftoside attenuated lipopolysaccharide-induced phosphorylation of ERK1/2 and mTOR. These results suggest that isoschaftoside can suppress inflammatory responses in lipopolysaccharide-activated microglia, and the mechanism was partly due to inhibition of the HIF-1α-mediated metabolic reprogramming pathway.

show abstract

“…Organotypic cultures of mouse optic nerves were performed as described previously ( 13 ) and cerebellar slice cultures were prepared using tissue isolated from mice aged postnatal day P10-12 as previously described ( 54 ). Optic nerves were removed with the retina intact and cerebellar slices were placed immediately in ice-chilled oxygenated artificial (a)CSF composed of: NaCl 133 mM, KCl 3 mM, CaCl2 1.5 mM, NaH2PO4 1.2 mM, HEPES buffer 10mMpH 7.3, 0.5% penicillin and streptomycin (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Drug connectivity mapping and functional analysis reveals therapeutic small molecules that differentially modulate myelination

Pieropan

Rivera

Williams

et al. 2020

Preprint

View full text Add to dashboard Cite

Oligodendrocytes are the myelin forming cells of the central nervous system (CNS) and are generated from oligodendrocyte progenitor cells (OPCs). Disruption or loss of oligodendrocytes and myelin has devastating effects on CNS function and integrity, which occurs in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease (AD) and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular regulatory pathways. Here, we have used a combined drug connectivity systems biology and neurobiological approach to identify compounds that exert positive and negative effects on oligodendroglia, depending on concentration. Notably, LY294002, a potent inhibitor of PI3K/Akt signalling, was the most highly ranked small molecule for both pro- and anti-oligodendroglial effects. We validated these in silico findings in multiple in vivo and ex vivo neurobiological models and demonstrate that low and high doses of LY294002 have a profoundly bipartite effect on the generation of OPCs and their differentiation into myelinating oligodendrocytes. Finally, we employed transcriptional profiling and signalling pathway activity assays to determine cell-specific mechanisms of action of LY294002 on oligodendrocytes and resolve optimal in vivo conditions required to promote myelin repair. These results demonstrate the power of multifactorial neurobiological and in silico strategies in determining the therapeutic potential of small molecules in neurodegenerative disorders.One-sentence summaryDrug discovery and CNS myelination

show abstract

The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination

Abstract: Graphical abstract

Cited by 21 publications

References 56 publications

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

Isoschaftoside Inhibits Lipopolysaccharide-Induced Inflammation in Microglia through Regulation of HIF-1α-Mediated Metabolic Reprogramming

Drug connectivity mapping and functional analysis reveals therapeutic small molecules that differentially modulate myelination

Contact Info

Product

Resources

About