title: Regulatory effects of caffeic acid phenethyl ester on neuroinflammation in microglial cells.
abstract: Microglial activation has been widely demonstrated to mediate inflammatory processes that are crucial in several neurodegenerative disorders. Pharmaceuticals that can deliver direct inhibitory effects on microglia are therefore considered as a potential strategy to counter balance neurodegenerative progression. Caffeic acid phenethyl ester (CAPE), a natural phenol in honeybee propolis, is known to possess antioxidant, anti-inflammatory and anti-microbial properties. Accordingly, the current study intended to probe the effects of CAPE on microglia activation by using in vitro and in vivo models. Western blot and Griess reaction assay revealed CAPE significantly inhibited the expressions of inducible nitric oxide synthase (NOS), cyclooxygenase (COX)-2 and the production of nitric oxide (NO). Administration of CAPE resulted in increased expressions of hemeoxygenase (HO)-1and erythropoietin (EPO) in microglia. The phosphorylated adenosine monophosphate-activated protein kinase (AMPK)-α was further found to regulate the anti-inflammatory effects of caffeic acid. In vivo results from immunohistochemistry along with rotarod test also revealed the anti-neuroinflammatory effects of CAPE in microglia activation. The current study has evidenced several possible molecular determinants, AMPKα, EPO, and HO-1, in mediating anti-neuroinflammatory responses in microglial cells.
authors.affiliation: Department of Biotechnology, Asia University, Taichung 413, Taiwan. tsaicf@asia.edu.tw.
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology, Asia University, Taichung 413, Taiwan. kuoyh@mail.cmu.edu.tw.|Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan. kuoyh@mail.cmu.edu.tw.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua 500, Taiwan. ibizayeh0816@hotmail.com.
authors.forename: Wei-Lan
authors.initials: WL
authors.lastname: Yeh
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 404, Taiwan. carenyujuwu@hotmail.com.
authors.forename: Caren Yu-Ju
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 404, Taiwan. lingirl831@hotmail.com.
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 404, Taiwan. wayson081024@yahoo.com.tw.
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Lai
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 404, Taiwan. yushuliu220@gmail.com.
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 404, Taiwan. lulu80620@yahoo.com.tw.
authors.forename: Ling-Hsuan
authors.initials: LH
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Asia University, Taichung 413, Taiwan. s123345142@gmail.com.
authors.forename: Jheng-Kun
authors.initials: JK
authors.lastname: Lu
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 404, Taiwan. dahyuu@mail.cmu.edu.tw.|Department of Photonics and Communication Engineering, Asia University, Taichung 413, Taiwan. dahyuu@mail.cmu.edu.tw.
authors.forename: Dah-Yuu
authors.initials: DY
authors.lastname: Lu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002109:Caffeic Acids; D004921:Erythropoietin; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D055372:AMP-Activated Protein Kinases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol