Cimifugin improves neuronal function in rat with focal cerebral ischemic injury by inhibiting oxidative stress, neuronal apoptosis and iNOS/COX-2 signaling pathway.

Abstract

Background: Cerebral ischemia-reperfusion (I/R) injury is a leading cause of long-term neurological disability and mortality, primarily due to oxidative stress, neuroinflammation, blood-brain barrier disruption, and neuronal apoptosis. Despite numerous therapeutic attempts, clinical translation of neuroprotective agents remains limited. This study investigates the neuroprotective potential of cimifugin, a flavonoid with antioxidant and anti-inflammatory properties, in a rat model of middle cerebral artery occlusion (MCAO).

Materials and methods: Rats were subjected to MCAO and treated with cimifugin (10, 20, and 30 mg/kg). Behavioral assessment was performed using the neurological deficit score and Morris Water Maze test. Brain infarct volume was evaluated using TTC staining. Histological and biochemical analyses were conducted to assess cerebral edema, oxidative stress markers (MDA, SOD, GSH), inflammatory cytokines (TNF-α, IL-1β, IL-6), apoptotic cell death (TUNEL assay), and expression of iNOS, and COX-2.

Results: Cimifugin significantly improved neurological outcomes in a dose-dependent manner, as indicated by reduced neurological deficit scores and enhanced cognitive performance in the Morris Water Maze test. TTC staining revealed a marked reduction in infarct volume, particularly at 30 mg/kg. Cimifugin attenuated cerebral edema and significantly decreased neuronal apoptosis. It reduced MDA levels while enhancing SOD and GSH activity, indicating robust antioxidative effects. Inflammatory cytokines (TNF-α, IL-1β, IL-6), as well as iNOS and COX-2 expression, were significantly downregulated.

Conclusions: Cimifugin confers neuroprotection in cerebral I/R injury through multi-targeted mechanisms involving antioxidant, anti-inflammatory, and anti-apoptotic actions. These findings suggest its potential as a low-toxicity, plant-derived candidate for managing ischemic stroke and related cerebrovascular diseases.