Casticin protected against neuronal injury and inhibited the TLR4/NF-κB pathway after middle cerebral artery occlusion in rats

Abstract

Although stroke is a major human neurological disease, there is a paucity of effective neuroprotectants that can improve its treatment. Casticin is a natural monomer drug with many biological effects such as anti-inflammatory and anti-tumor actions. However, it is not clear whether it has a neuroprotective effect in ischemic stroke. In this study, the neuroprotective effect of casticin in a rat middle cerebral artery occlusion (MCAO) model was investigated. Results showed that casticin reduced the volume of the cerebral infarction, mNSS scores, swimming distance, time to find the submerged platform, and serum concentrations of TNF-α, TGF-β, IL-6 in MCAO rats. Moreover, casticin also decreased the expression of TLR4, NF-κB p65, and NF-κB p50 proteins and reversed the reduced expression of IκB protein in the brain tissue of MCAO rats. The in vitro study revealed that casticin decreased apoptosis of OGD/R-PC12 cells, reduced the expression of TLR4, NF-κB p65, and NF-κB p50, while increased IκB protein expression. In conclusion, casticin improved the neurological functions of MCAO rats via inhibiting the TLR4/NF-κB pathway and might have the potential to be developed into a neuroprotective agent for stroke patients.

Keywords: TLR4/NF-κB pathway; casticin; neuroprotective; stroke.