title: Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2E,6E)-2,6-bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH).
abstract: The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•- quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63-5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. aoguizhen@suda.edu.cn.
authors.forename: Gui-Zhen
authors.initials: GZ
authors.lastname: Ao
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. cxj945@163.com.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Chu
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. yuanyuanji11@gmail.com.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ji
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. jwwang@suda.edu.cn.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D003512:Cyclohexanones / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D016877:Oxidants / Q000494:pharmacology; D016716:PC12 Cells; D010851:Picrates / Q000037:antagonists & inhibitors / Q000378:metabolism; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C000595158:2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone; D000975:Antioxidants; D001713:Biphenyl Compounds; D003512:Cyclohexanones; D016166:Free Radical Scavengers; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D016877:Oxidants; D010851:Picrates; D028321:Plant Preparations; D020011:Protective Agents; D013481:Superoxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione; D003474:Curcumin