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

Tae-Kyeong Lee,Young-Myeong Kim,Jae-Chul Lee,Moo-Ho Won,Il-Jun Kang,Bora Kim,Myoung Cheol Shin,Jun Hwi Cho,Hye Jin Sim,Ji Hyeon Ahn,Dae- Won Kim,Joon Ha Park,Soo Young Choi,Sungwoo Ryoo

doi:10.3390/molecules25163578

Abstract

Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is among the phenolic acid compounds which can be naturally found in green coffee extract and tea. CGA has been studied since it displays significant pharmacological properties. The aim of this study was to investigate the effects of CGA on cognitive function and neuroprotection including its mechanisms in the hippocampus following transient forebrain ischemia in gerbils. Memory and learning following the ischemia was investigated by eight-arm radial maze and passive avoidance tests. Neuroprotection was examined by immunohistochemistry for neuronal nuclei-specific protein and Fluoro-Jade B histofluorescence staining. For mechanisms of the neuroprotection, alterations in copper, zinc-superoxide dismutase (SOD1), SOD2 as antioxidant enzymes, dihydroethidium and 4-hydroxy-2-nonenal as indicators for oxidative stress, and anti-inflammatory cytokines (interleukin (IL)-4 and IL-13) and pro-inflammatory cytokines (tumor necrosis factor α (TNF-α) and IL-2) were examined by Western blotting and/or immunohistochemistry. As a result, pretreatment with 30 mg/kg CGA attenuated cognitive impairment and displayed a neuroprotective effect against transient forebrain ischemia (TFI). In Western blotting, the expression levels of SOD2 and IL-4 were increased due to pretreatment with CGA and, furthermore, 4-HNE production and IL-4 expressions were inhibited by CGA pretreatment. Additionally, pretreated CGA enhanced antioxidant enzymes and anti-inflammatory cytokines and, in contrast, attenuated oxidative stress and pro-inflammatory cytokine expression. Based on these results, we suggest that CGA can be a useful neuroprotective material against ischemia-reperfusion injury due to its antioxidant and anti-inflammatory efficacies.

Highlights

A brief period of ischemic condition in the brain causes ischemia-reperfusion injury, and it leads to selective neuronal loss/death in brain regions vulnerable to ischemia-reperfusion injury, such as the neocortex, hippocampus and striatum [1,2,3,4]
It has been reported that pretreated Oenanthe Javanica extract rich in Chlorogenic acid (CGA) exerts neuroprotective effects in the gerbil hippocampus following transient forebrain ischemia (TFI) via enhancement of antioxidant enzymes and regulation of anti- and pro-inflammatory cytokines [17,18]
It has been demonstrated that CGA

Summary

Introduction

A brief period of ischemic condition in the brain causes ischemia-reperfusion injury, and it leads to selective neuronal loss/death in brain regions vulnerable to ischemia-reperfusion injury, such as the neocortex, hippocampus and striatum [1,2,3,4]. Transient forebrain ischemia (TFI) for 5 min causes death of pyramidal neurons in the hippocampal Cornu Ammonis 1 (CA1) region. The neuronal loss/death following 5 min TFI occurs from 4 or 5 days after TFI; this phenomenon is termed as the “delayed neuronal death” [2,5]. Many studies on the mechanisms regarding to the delayed neuronal death following transient brain ischemia are constantly carried out. Based on the above-mentioned mechanisms, neuroprotective materials against transient ischemic injury were investigated [10,11]

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