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,
Il-Jun Kang,
Bora Kim,
Hye Jin Sim,
Dae- Won Kim,
Ji Hyeon Ahn,
Jae-Chul Lee,
Sungwoo Ryoo,
Myoung Cheol Shin,
Jun Hwi Cho,
Young-Myeong Kim,
Joon Ha Park,
Soo Young Choi,
Moo-Ho Won
Affiliations
Tae-Kyeong Lee
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Korea
Il-Jun Kang
Department of Food Science and Nutrition, Hallym University, Chuncheon, Gsangwon 24252, Korea
Bora Kim
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Hye Jin Sim
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Dae- Won Kim
Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, Gangneung, Gangwon 25457 Korea
Ji Hyeon Ahn
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Korea
Jae-Chul Lee
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Sungwoo Ryoo
Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Myoung Cheol Shin
Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Jun Hwi Cho
Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Young-Myeong Kim
Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Joon Ha Park
Department of Anatomy, College of Oriental Medicine, Dongguk University-Gyeongju, Gyeongju, Gyeongbuk, 38066, Korea
Soo Young Choi
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Korea
Moo-Ho Won
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
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.
