Isoliquiritin protects neural function by inhibiting glial cell-mediated neuroinflammation through the NF-κB /AIM2 signaling pathway.

Abstract

BACKGROUND AND OBJECTIVE: Ischemic stroke remains a major global health challenge, with current therapies limited by narrow treatment windows and modest efficacy. Isoliquiritin (ISL), a natural flavonoid with known anti-inflammatory and antioxidant activities, has demonstrated neuroprotective effects in ischemia-reperfusion models. This study investigated the mechanisms by which ISL mitigates neuroinflammation and protects neurons following ischemic stroke. METHODS: BV2 microglia underwent 2 hours of oxygen-glucose deprivation followed by reperfusion after 30 minutes of ISL pretreatment. Cell viability was assessed using the CCK-8 assay. NF-κB/AIM2 pathway activation and related mRNA expression were evaluated by Western blot, RT-qPCR, immunofluorescence, and ELISA. For in vivo assessment, transient middle cerebral artery occlusion (MCAO) was performed in rats to induce ischemia-reperfusion injury. Neurological function was assessed by behavioural testing, infarct size was quantified using TTC staining, and histopathological changes were evaluated using hematoxylin-eosin and Nissl staining. RESULTS: ISL treatment significantly reduced inflammatory responses and improved the survival of OGD-exposed microglia, accompanied by suppression of NF-κB/AIM2 signaling. In MCAO rats, ISL dose-dependently decreased infarct volume, improved neurological outcomes, and inhibited the expression of pathway-related proteins. CONCLUSION: ISL attenuates neuroinflammation and neuronal damage after ischemic stroke by inhibiting the NF-κB/AIM2 signaling axis. These results elucidate that ISL attenuates neuroinflammation and neuronal damage by inhibiting the NF-κB/AIM2 signaling axis, indicating its promise as a potential therapeutic candidate for ischemic stroke.