Abstract
This study investigated the effect of dihydrocapsaicin (DHC) on cerebral and blood brain barrier (BBB) damage in cerebral ischemia and reperfusion (I/R) models. The models were induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The rats were divided into five groups: sham, or control group; vehicle group; and 2.5 mg/kg, 5 mg/kg, and 10 mg/kg BW DHC-treated I/R groups. After 24 h of reperfusion, we found that DHC significantly reduced the area of infarction, morphology changes in the neuronal cells including apoptotic cell death, and also decreased the BBB damage via reducing Evan Blue leakage, water content, and ultrastructure changes, in addition to increasing the tight junction (TJ) protein expression. DHC also activated nuclear-related factor-2 (Nrf2) which involves antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx), and significantly decreased oxidative stress and inflammation via down-regulated reactive oxygen species (ROS), NADPH oxidase (NOX2, NOX4), nuclear factor kappa-beta (NF-ĸB), and nitric oxide (NO), including matrix metalloproteinases-9 (MMP-9) levels. DHC protected the cerebral and the BBB from I/R injury via attenuation of oxidative stress and inflammation. Therefore, this study offers to aid future development for protection against cerebral I/R injury in humans.
Highlights
Defense is nuclear-related factor-2 (Nrf2), an anti-inflammatory pathway which is associated with antioxidants that inhibit oxidative stress and anti-inflammation response
In this study, we firstly investigate the underlying mechanism of DHC to attenuate cerebral and blood brain barrier (BBB) damage in ischemia and reperfusion (I/R) rat models mediated by NF-κB and Nrf[2] signaling pathways
Previous studies have reported that NOX2 and NOX4 are the main sources of reactive oxygen species (ROS) in cerebral I/R injury[12]
Summary
Defense is nuclear-related factor-2 (Nrf2), an anti-inflammatory pathway which is associated with antioxidants that inhibit oxidative stress and anti-inflammation response. Several lines of evidence have demonstrated that extracts from capsaicinoids have multiple pharmacological and physiological effects, including anti-cancer, anti-inflammation, antioxidant, anti-obesity, and pain relief[16,17,18,19]. It is possible that DHC, a compound in capsaicinoids, may decrease oxidative stress and inflammation in I/R injury. We firstly demonstrate that DHC attenuates cerebral and BBB damage in I/R rat models via reducing oxidative stress and inflammation, and promoting the antioxidative pathway. We investigate the protective effect of DHC on the BBB and cerebral damage from middle cerebral artery occlusion and reperfusion in Wistar rats by determining oxidative stress and inflammation. Our data suggest that DHC is a neuroprotective agent against cerebral ischemia and reperfusion via attenuation of BBB and cerebral damage, and warrants further evaluation
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