Ligustroflavone exerts neuroprotective activity through suppression of NLRP1 inflammasome in ischaemic stroke mice.

Abstract

Inflammation is thought to play an important role in the pathophysiology of ischaemic stroke, which is a main cause of disability and morbidity worldwide. Inhibition of the NOD-like receptor protein 1 (NLRP1) inflammasome has been reported to alleviate the inflammatory response in cell and animal models. Ligustroflavone (LIG) is a compound derived from Ligustrum lucidum, which shows anti-inflammatory activity and may play a beneficial role in a number of neurological diseases. To date, the potential for LIG to act through NLRP1 as a treatment for ischemic stroke has not been studied. The present study established an ischaemic stroke model by middle cerebral artery occlusion (MCAO). Modified neurological severity scoring, open-field and the Rotarod test were used to assess neurological deficits. Staining with Hoechst 33258 and western blotting were used to evaluate neuronal damage. Expression levels of NLRP1 inflammasome complexes and inflammatory cytokines were determined using western blotting, enzyme-linked immunosorbent assay and reverse transcription-quantitative PCR. Treatment with LIG minimized the impairment of neurological function and blocked neuronal damage in MCAO mice. In addition, treatment with LIG attenuated the upregulation of expression levels of the NLRP1 inflammasome complexes and the inflammatory cytokines TNF-α, IL-18, IL-6 and IL-1β. Overall, LIG played an important role in anti-inflammatory and neuroprotective activity in MCAO models of ischaemic stroke.