Isoliquiritigenin regulates microglial M1/M2 polarisation by mediating the P38/MAPK pathway in cerebral stroke

Objectives: Regulation of microglia polarisation may be a new way to treat ischaemic stroke based on its effects on brain injury. Isoliquiritigenin (ILG) is a flavonoid with neuroprotective function. The study investigated whether ILG regulated microglial polarisation and affects brain injury.

Methods: Here, a transient middle cerebral artery occlusion (tMCAO) model in vivo and lipopolysaccharide (LPS)-induced BV2 cells in vitro were established. Brain damage was assessed using a 2,3,5-triphenyl-tetrazolium-chloride staining assay. Microglial polarisation was analysed using Enzyme linked immunosorbent assay, quantitative real-time polymerase chain reaction, and immunofluorescence assay. The levels of p38/MAPK pathway-related factors were measured by western blot.

Key findings: ILG suppressed infarct volume and neurological function of tMCAO rats. Moreover, ILG facilitated M2 microglia polarisation and suppressed M1 polarisation in the tMCAO model and LPS-induced BV2 cells. Moreover, ILG reduced the phosphorylation of p38, MAPK activated protein kinase 2, and heat shock protein 27 induced by LPS. Rescue study showed that activating the p38/MAPK pathway reversed the microglia polarisation induced by ILG and inactivating the p38/MAPK pathway enchanced the microglia polarisation.

Conclusion: ILG promoted microglia M2 polarisation by inactivating the p38/MAPK pathway, suggesting that ILG has the potential for the treatment of ischaemic stroke.

Isoliquiritigenin; cerebral stroke; microglia polarisation; p38 MAPK pathway.