Journal of Neurogastroenterology and Motility
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Korean J Physiol Pharmacol 2016 May; 20(3): 279-286
Jia Bak1, Hee Jung Kim2, Seong Yun Kim3, and Yun-Sik Choi1,*
Neuroprotective effect of caffeic acid phenethyl ester in 3-nitropropionic acid-induced striatal neurotoxicity
1Department of Pharmaceutical Science and Technology, College of Health and Medical Science, Catholic University of Daegu, Gyeongsan 38430, 2Department of Physiology, College of Medicine, Dankook University, Cheonan 31116, 3Department of Pharmacology, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington’s disease (HD). Initially, to test CAPE’s antioxidant activity, a 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radicalscavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/ kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD.
Keyword : 3-nitropropionic acid, Antioxidant, Caffeic acid phenethyl ester, Huntington’s disease, Striatum