title: Pinocembrin attenuates MPP(+)-induced neurotoxicity by the induction of heme oxygenase-1 through ERK1/2 pathway.
abstract: Our recent study demonstrated that pinocembrin (PB), the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl-4-phenylpyridinium (MPP(+))-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB increased heme oxygenase-1 (HO-1) expression, which conferred protection against MPP(+)-induced cytotoxicity, because the inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of PB. PB induced the phosphorylation of ERK1/2, and its cytoprotective effect was abolished by ERK1/2 inhibitors. Meanwhile, we have shown that MPP(+) induce the expression in a concentration-dependent manner in SH-SY5Y cells, which was further enhanced by PB. Taken together, the results suggest that PB enhances HO-1 expression to suppress MPP(+)-induced oxidative damage via ERK1/2 signaling pathways. These results revealed the mechanisms of PB enhances HO-1 expression, and contribute to shed some light on the mechanisms whereby PB inhibits the MPP(+)-induced neurotoxicity. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Department of Neurology, Affiliated Hospital of Chifeng University, Chifeng 024005, PR China. Electronic address: whongquan@alu.fudan.edu.cn.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Central Lab, Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Linan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Qifu
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: dugh@imm.ac.cn.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D044950:Flavanones; D018696:Neuroprotective Agents; C016063:pinocembrin; D051547:Heme Oxygenase-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015655:1-Methyl-4-phenylpyridinium
keywords: Heme oxygenase-1; MPP(+); Neuroprotection; Parkinson’s disease; Pinocembrin