Chlorogenic acid alleviates cerebral ischemia-induced neuroinflammation via attenuating nuclear factor kappa B activation.

Ischemic stroke is the most common type of stroke and is caused by vascular closure. Chlorogenic acid is a polyphenolic compound that is present in various plants. It is used as a traditional oriental medicine because of its anti-oxidant and anti-inflammatory properties. We investigated whether chlorogenic acid mediates neuroprotective effects by regulating pro-inflammatory proteins. Focal cerebral ischemia was induced through middle cerebral artery occlusion (MCAO) surgery in adult rats. Chlorogenic acid (30 mg/kg) or vehicle was injected into the abdominal cavity 2 h after MCAO. Rats were sacrificed 24 h after MCAO surgery and brain tissues were isolated immediately. MCAO caused histopathological changes in the ischemic cerebral cortex, and chlorogenic acid attenuated these changes. Chlorogenic acid reduced MCAO-induced reactive oxygen species generation and oxidative stress increase in the cerebral cortex. Furthermore, cerebral ischemia increased the expression of ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP), which are microglia and astrocyte activation markers, respectively. However, chlorogenic acid prevented MCAO-induced these increases. MCAO damage also increased the expression of nuclear factor-κB (NF-κB), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). Chlorogenic acid treatment attenuated these increases caused by MCAO. These proteins are representative pro-inflammatory markers. This study confirmed that chlorogenic acid exerts an anti-oxidative effect and elucidated anti-inflammatory effect through regulating NF-κB, IL-1ß, and TNF-α on cerebral ischemia. Thus, we can suggest that chlorogenic acid has neuroprotective effects by reducing oxidative stress and controlling pro-inflammatory proteins against cerebral ischemic damage.

Epigallocatechin Gallate Alleviates Down-Regulation of Thioredoxin in Ischemic Brain Damage and Glutamate-Exposed Neuron.

Epigallocatechin gallate (EGCG) is one of polyphenol that is abundant in green tea. It has anti-oxidative activity and exerts neuroprotective effects in ischemic brain damage. Ischemic conditions induce oxidative stress and result in cell death. Thioredoxin is a small redox protein that plays an important role in the regulation of oxidation and reduction. This study was designed to investigate the regulation of thioredoxin by EGCG in ischemic brain damage. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia in male Sprague-Dawley rats. The EGCG (50 mg/kg) or was administered before MCAO surgical operation. Neurological behavior test, reactive oxygen species (ROS), and lipid peroxidation (LPO) measurement were performed 24 h after MCAO. The cerebral cortex was isolated for further experiments. EGCG alleviated MCAO-induced neurological deficits and increases in ROS and LPO levels. EGCG also ameliorated the decrease in thioredoxin expression by MCAO. This finding was confirmed using various techniques such as Western blot analysis, reverse transcription PCR, and immunofluorescence staining. Results of immunoprecipitation showed that MCAO decreases the interaction between apoptosis signal-regulating kinase 1 (ASK1) and thioredoxin, while EGCG treatment attenuates this decrease. EGCG also attenuated decrease of cell viability and thioredoxin expression in glutamate-exposed neuron in a dose-dependent manner. It alleviated the increase of caspase-3 by glutamate exposure. However, this effect of EGCG on caspase-3 change was weakened in thioredoxin siRNA-transfected neurons. These findings suggest that EGCG exerts a neuroprotective effect by regulating thioredoxin expression and modulating ASK1 and thioredoxin binding in ischemic brain damage.