Shionone protects cerebral ischemic injury via alleviating microglia-mediated neuroinflammation

Microglia are the resident immune cells in the central nervous system (CNS). In the acute phase of ischemic brain injury, microglia in the semi-dark band rapidly change from resting to active state, mediating the pro-inflammatory response to aggravate the injury, and if the pro-inflammatory response of microglia in the semi-dark band is targeted at this time, it will effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the Asteraceae aster, was previously reported to regulate the inflammatory response of macrophage in sepsis-induced acute lung injury, while its function in post-stroke neuroinflammation, especially microglia-mediated neuroinflammation, remains uninvestigated. Here we found that SH significantly inhibited LPS-induced elevation of inflammatory cytokines in microglia in vitro, including IL-1β, TNF-α, and iNOS. Moreover, our results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which might be contributed by the inhibition of microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited phosphorylation of serine-threonine protein kinase (AKT) -a target of rapamycin (mTOR) -signal transducer and activator of transcription 3 (STAT3). These findings suggested that SH may be a potential therapeutic agent for relieving ischemic stroke via alleviating microglia-associated neuroinflammation.