The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination

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.