Lithium co-administration with rutin improves post-stroke neurological outcomes via suppressing Gsk-3β activity in a rat model

Abstract

Cerebral ischemic stroke is one of the leading causes of adult disability worldwide. Reperfusion is the only therapeutic option with a lot of side effects. In the current study, we investigated the efficacy of rutin and lithium co-treatment in improving post-stroke neurological outcomes in a transient global cerebral ischemia-reperfusion injury rat model. Middle-aged male rats were subjected to transient global cerebral ischemia-reperfusion. NORT and Y-maze were used to assess the cognitive processes. Lipid peroxidation, protein carbonylation, and nitric oxide assays were performed to study oxidative stress. The excitotoxicity index was calculated by HPLC. Real time-PCR and western blotting were performed to study gene and protein expressions. The co-administration of rutin and lithium improved the overall survival, recognition memory, spatial working memory, and neurological score following cerebral ischemia-reperfusion in rats. Further, a marked decrease in malonaldehyde, protein carbonyls, and nitric oxide levels was observed following combined treatment. The mRNA expression of antioxidant (Hmox1 and Nqo1) and pro-inflammatory (Il2, Il6, and Il1β) markers were significantly attenuated in the rutin and lithium co-administrated group. The treatment inhibited the Gsk-3β and maintained a normal pool of the downstream β-catenin and Nrf2 proteins. The results revealed that co-administration of rutin and lithium had a neuroprotective potential, suggesting it to be a viable treatment to overcome post-stroke deaths and neurological complications.