Chlorogenic acid ameliorates memory loss and hippocampal cell death after transient global ischemia

Abstract

Chlorogenic acid (CGA) is known to have antioxidant potentials, yet the effect of CGA on brain ischemia has not been sufficiently understood. Brain ischemia such as transient global ischemia disrupts many areas of the brain of rats, including the hippocampus. Male Wistar rats were randomly assigned into five groups, that is, sham‐operated (SO), bilateral common carotid occlusion (BCCO), and BCCO+ 15, 30, and 60 mg/kg bw CGA groups (CGA15, CGA30, and CGA60, respectively). Brain ischemia was induced in Wistar rats with BCCO for 20 min followed by intraperitoneal injection of CGA. The rats were examined for the spatial memory in a Morris water maze test on the 3rd day and were euthanized on the 10th day after BCCO. The total number of pyramidal cells was estimated, and the mRNA expressions of Bcl2, Bax, caspase‐3, SOD2, SOD1, GPx, ET‐1, eNOS, CD31, and VEGF‐A were measured. The BCCO group spent less time and distance in the target quadrant than any other group in the spatial memory retention test. The CA1 pyramidal cell numbers in the BCCO and CGA15 groups were lower than in the CGA30 and CGA60 groups. The mRNA expressions of Bcl2, SOD2, and CD31 in the BCCO group were lower than in the CGA15, CGA30, and CGA60 groups. The ET‐1 expression was higher in the BCCO and CGA15 groups than in the SO, CGA30, and CGA60 groups. CGA improves the spatial memory and prevents the CA1 pyramidal cell death after BCCO by increasing Bcl2, SOD2, and CD31 expressions and decreasing ET‐1 expression.

Chlorogenic acid: A comprehensive review of the dietary sources, processing effects, bioavailability, beneficial properties, mechanisms of action, and future directions

“…Furthermore, a recent study showed that 5‐CQA reduces brain damage, nerve damage, and volume of cerebral infarction and neuronal apoptosis by regulating the NFE2L2 signaling pathway in CI‐reperfusion (CI/R)‐induced oxidative stress in rats (Liu, Wang, Zhang, & Zhang, 2020). According to Hermawati, Arfian, Mustofa, and Partadiredja (2020), 5‐CQA improved spatial memory and prevented the degeneration of hippocampal CA1 pyramidal cells in CI/R rats, which may be attributed to increased expression of Bcl2 , platelet endothelial cell adhesion molecule ( Pecam1 , also known as Cd31 ), and superoxide dismutase [Mn], mitochondrial ( Sod2 ), as well as the suppression of the expression of endothelin‐1 ( Edn1 , also known as Et‐1 ).…”

Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

“…Hermawati et al (2020) investigated whether CGA treatment attenuated spatial memory decline by a Morris water maze test in rats subjected to transient ischemia induced by bilateral common carotid arteries occlusion (BCCAO) and found no significant differences in escape latency from the 3rd trial between the sham-operated and BCCAO-operated groups [ 14 ]. However, we examined not only spatial memory (by 8-ARMT) but also short-term memory test (by PAT) and found significant differences in the number of errors and latency time between the sham-operated group and TFI-operated group.…”

“…However, in the case of the rat model used by Hermawati et al (2020), blood supply to the forebrain is not totally stopped when the rats were given BCCAO because of the presence of posterior communicating arteries in the Willis circle. In addition, many of the CA1 pyramidal neurons in the rat model (79.4% of the sham-operated rats) were found after BCCAO [ 14 ]. However, in our gerbil model, a few CA1 pyramidal neurons (10.2% of the sham group) were detected after TFI.…”

“…CGA has been investigated to display neuroprotective potentiality against ischemic insults in various experimental animal models of cerebral ischemia. For example, Hermawati et al (2020) described that 30 and 60 mg/kg CGA protected hippocampal pyramidal neurons following 20 min of TFI induced by occlusion of bilateral common carotid arteries in rats [ 14 ]. Additionally, Lee K et al (2012) reported that 30 mg/kg CGA reduced infarct volume in the brain of a rat model of focal brain ischemia induced by middle cerebral artery occlusion for 2 h [ 34 ].…”

“…It has been reported that pretreatment with CGA attenuates neuronal loss in the cerebral cortex following transient focal brain ischemia induced by middle cerebral artery occlusion in rats [ 13 ]. Furthermore, the therapeutic administration of CGA attenuates cognitive and memory impairment and protects hippocampal neurons through its antioxidant and anti-apoptotic attributes in a rat model of transient global cerebral ischemia [ 14 ].…”