Dihydrocapsaicin Attenuates Blood Brain Barrier and Cerebral Damage in Focal Cerebral Ischemia/Reperfusion via Oxidative Stress and Inflammatory

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.

Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

“…To add insult to brain injury, inflammatory processes are being correlated with alterations in cellular metabolism (Yin et al, ). Numerous compounds are medicative in brain disorders depending on their antioxidant and anti‐inflammatory activity (Abdelsalam & Safar, ; Habtemariam, ; Janyou et al, ; Shal, Ding, Ali, Kim, & Khan, ). On the other hand, oxidative stress and inflammation also play crucial roles in BBB injury (Janyou et al, ; Zhang, Jiang, et al, ).…”

“…Numerous compounds are medicative in brain disorders depending on their antioxidant and anti-inflammatory activity (Abdelsalam & Safar, 2015;Habtemariam, 2019;Janyou et al, 2017;Shal, Ding, Ali, Kim, & Khan, 2018). On the other hand, oxidative stress and inflammation also play crucial roles in BBB injury (Janyou et al, 2017;Zhang, Jiang, et al, 2017).…”

“…Numerous compounds are medicative in brain disorders depending on their antioxidant and anti-inflammatory activity (Abdelsalam & Safar, 2015;Habtemariam, 2019;Janyou et al, 2017;Shal, Ding, Ali, Kim, & Khan, 2018). On the other hand, oxidative stress and inflammation also play crucial roles in BBB injury (Janyou et al, 2017;Zhang, Jiang, et al, 2017). Strong evidence indicates that excessive ROS generation may cause TJs degradation and BBB dysfunction, which lead to exogenous detrimental large molecules freely cross the barrier into the brain and further indirectly accelerate the progress of brain disorders (Cheon et al, 2016).…”

“…Oxidative stress and inflammation are well‐known mechanisms accounting for BBB dysfunction (Janyou et al, ; Zhang et al, ). Excessive generation of reactive oxygen species (ROS) or pro‐inflammatory cytokines (e.g., IL‐1β and TNF‐α) probably result in TJs degradation and BBB disruption, which may further lead magnitude of xenobiotics to extravasate into brain parenchyma and aggravate the brain tissue damage (Cheon et al, ; Da Fonseca et al, ).…”

Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer’s Disease Based on Systems Biology

“…Six groups of AD rats were administered intragastrically with KXS (10.0 g/kg), GR (3.0 g/kg), PR (2.0 g/kg), PO (3.0 g/kg), AT (2.0 g/kg), and Hup A (0.027 mg/kg) once a day from the third week until the end of the experiment [25]. At the end of the fourth week, the stereotaxic injection of 4 μg Aβ [25][26][27][28][29][30][31][32][33][34][35] (1 μg/μL) was operated at the following coordinates: anteroposterior-3.5; mediolateral-+2.0; and dorsoventral-2.8 mm [26]. Two weeks later, the Morris water maze test was used for evaluation.…”