title: Inhibition of beta-amyloid-induced neurotoxicity by pinocembrin through Nrf2/HO-1 pathway in SH-SY5Y cells.
abstract: Amyloid beta peptide (Aβ) can cause neurotoxicity in Alzheimer's disease (AD). It evokes a cascade of oxidative damage to neurons. Pinocembrin (PCB), the most abundant flavonoid in propolis, has been proven to have neuroprotective effects in vivo and in vitro. In the present study, we investigated the neuroprotective effects of PCB on Aβ25-35-induced neurotoxicity. Exposure of SH-SY5Y cells to 25μM Aβ25-35 for 24h caused viability loss, apoptotic increase and reactive oxygen species (ROS) increase, pre-treatment with PCB for 4h significantly reduced the viability loss, apoptotic rate and attenuated Aβ-mediated ROS production. PCB strikingly inhibited Aβ25-35-induced mitochondrial dysfunctions, including lowered membrane potential, decreased Bcl-2/Bax ratio. In addition, PCB suppressed the release of cytochrome c and the cleavage of caspase-3. PCB treatment also resulted in an increase in Nrf2 protein levels and subsequent induction of heme oxygenase-1(HO-1) expression in SH-SY5Y cells. RNA interference-mediated knockdown of Nrf2 expression suppressed the PCB-induced HO-1 expression. Notably, we found that the HO-1 inhibitor zinc protoporphyrin IX (ZnPP) markedly diminished the neuroprotective effect of PCB against Aβ-mediated neurotoxicity. Taken together, these results indicated that PCB protects SH-SY5Y cells from Aβ25-35-induced neurotoxicity through activation of Nrf2/HO-1 pathways. Thus, activation of Nrf2/HO-1 pathways and inhibition of mitochondria-dependent apoptosis together may protect cells from Aβ25-35-induceded neurotoxicity.
authors.affiliation: Chifeng Medical College, Chifeng University, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China; Department of Oncology, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, PR China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Miao
authors.affiliation: 2012 MBBS, Chifeng Medical College, Chifeng University.
authors.forename: Aamina Zia
authors.initials: AZ
authors.lastname: Mir
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Chifeng Medical College, Chifeng University, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Central Lab, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Linan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Neurology, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Qifu
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Neurology, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Chifeng Medical College, Chifeng University, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China; Department of Central Lab, the Affiliated Hospital of Chifeng University, Chifeng 024005, PR China; Department of Neurology, the 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
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D044950:Flavanones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C016063:pinocembrin; D045304:Cytochromes c; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Alzheimer's disease; Beta amyloid; Heme oxygenase-1; Neuroprotection; Nrf2; Pinocembrin