Pharmacodynamic Effect of Ellagic Acid on Ameliorating Cerebral Ischemia/Reperfusion Injury

Abstract

Cerebral ischemia/reperfusion (I/R) injury causes a larger population of disable patients and deaths annually. Three Tibetan prescriptions have been applied in alleviating the I/R injury for a 1,000 years. Interestingly, ellagic acid (EA) is one of the commonly dominated phytochemicals in these 3 prescriptions. Therefore, it is noteworthy to evaluate the association between the pharmacodynamics effects of EA and I/R injury alleviation. In this study, we reveal that the EA can effectively reduce the infarction area, and prevent the neuron from apoptosis and damage in permanent middle cerebral artery occlusion rat model. The results of the histopathological study indicate that alleviation of brain damage is positively correlated with the EA dose. Further by biochemical analysis, it indicates that the EA can alleviate the brain damage by the anti-inflammatory and anti-oxidative response mediated by EA. The upregulation of zonula occludens-1 and down-regulation of Aquaporin 4 and matrix metalloprotein 9 (MMP-9) in injured brain tissues after being treated with EA suggested that the reconstruction of brain-blood-barrier (BBB), which can further prevent the brain from further injury by the other xenobiotics. In addition, EA will not activate the coagulation factors XII to induce coagulation formation during the treatment process. Therefore, EA is a promising candidate oral drug for I/R injury therapy.

Oenothein B, a Bioactive Ellagitannin, Activates the Extracellular Signal-Regulated Kinase 2 Signaling Pathway in the Mouse Brain

“…Figure 3 shows the representative bands of a Western blot for total CREB (CREB), phosphorylated CREB (pCREB), and pCREB/CREB ratios, indicating that the pCREB/CREB ratio on day 7 was slightly higher in the OeB (100 mg/kg/day)-treated group (OeB) than in the vehicle group, but no significant difference was observed, contrary to our expectation (p = 0.0866). Recent studies showed that ellagic acid has neuroprotective functions in the brain [19][20][21][22]. For example, the subchronic p.o.…”

“…Recent studies showed that ellagic acid has neuroprotective functions in the brain [19][20][21][22]. For example, the subchronic p.o.…”

Hydroxysafflor Yellow A Together with Blood–Brain Barrier Regulator Lexiscan for Cerebral Ischemia Reperfusion Injury Treatment

“… 34 As shown in Figure 3 B,C, the expression of P-gp was down-regulated by Lex, which was consistent with a previous report. 35 F-actin is composed of two intracellular filamentous structures, including microfilaments and filaments. It is an endothelial cytoskeletal protein in BBB that is involved in cell attachment and cell morphology retention and establishment.…”

“…EB leakage was used to assess BBB permeability. 35 In brief, 5 d after reperfusion, the rats were injected with 2% EB (4 mL/kg) via the tail vein to evaluate the permeability change of BBB. Rats were perfused 2 h later with PBS until the perfusate turned clear.…”

“…After 8 h of moisture removal, the weights of the samples ( W 2 ) were measured again. 35 The ratio of the water content in each group was calculated using the following formula: …”