The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination
| Autor: | Manoelito Coelho dos Santos Junior, Francesca Pieropan, Arthur M. Butt, Juceni P. David, Larissa de Mattos Oliveira, Cleide dos Santos Souza, Victor Diogenes Amaral da Silva, Monique Marylin Alves de Almeida, Jorge Mauricio David, Silvia Lima Costa |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Anti-Inflammatory Agents Estrogen receptor APC-PAID Estrogen receptors Tissue Culture Techniques Mice 0302 clinical medicine Neuroinflammation Cerebellum Agathisflavone Demyelinating disease Myelin Sheath Microglia Chemistry BB/M029379/1 Cell Differentiation Oligodendroglia medicine.anatomical_structure Phenotype BBSRC 030220 oncology & carcinogenesis Cytokines Female Neuroimmunomodulation Central nervous system Green Fluorescent Proteins Mice Transgenic Article 03 medical and health sciences Immune system medicine Animals Biflavonoids Remyelination Cell Proliferation ComputingMethodologies_COMPUTERGRAPHICS Pharmacology Flavonoids Multiple sclerosis Estrogen Receptor alpha Lysophosphatidylcholines RCUK medicine.disease Mice Inbred C57BL 030104 developmental biology Neuroscience |
| Zdroj: | Almeida, M M A D, Pieropan, F, de Mattos Oliveira, L, dos Santos Junior, M C, David, J M, David, J P, da Silva, V D A, dos Santos Souza, C, Lima Costa, S & Butt, A 2020, ' The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination ', Pharmacological Research, vol. 159, 104997 . https://doi.org/10.1016/j.phrs.2020.104997 Pharmacological Research |
| Popis: | Graphical abstract Highlights • Agathisflavone enhances remyelination through modulating neuroinflammation. • Agathisflavone induces a polarization in microglia from an M1 to an M2-like phenotype. • Agathisflavone interacts with the nuclear receptors RAR, RXRα, RXRγ, ERα, and ERβ. • Remyelination effect of agathisflavone was via ER, with a greater effect of ERα. Myelin loss is the hallmark of the demyelinating disease multiple sclerosis (MS) and plays a significant role in multiple neurodegenerative diseases. A common factor in all neuropathologies is the central role of microglia, the intrinsic immune cells of the central nervous system (CNS). Microglia are activated in pathology and can have both pro- and anti-inflammatory functions. Here, we examined the effects of the flavonoid agathisflavone on microglia and remyelination in the cerebellar slice model following lysolecithin induced demyelination. Notably, agathisflavone enhances remyelination and alters microglial activation state, as determined by their morphology and cytokine profile. Furthermore, these effects of agathisflavone on remyelination and microglial activation were inhibited by blockade of estrogen receptor α. Thus, our results identify agathisflavone as a novel compound that may act via ER to regulate microglial activation and enhance remyelination and repair. |
| Databáze: | OpenAIRE |
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