title: Robinetinidol-(4beta-->8)-epigallocatechin 3-O-gallate, a galloyl dimer prorobinetinidin from Acacia mearnsii De Wild, effectively protects human neuroblastoma SH-SY5Y cells against acrolein-induced oxidative damage.
abstract: Acrolein is a highly electrophilic alpha, beta-unsaturated aldehyde to which humans are exposed in many situations and has been implicated in neurodegenerative diseases such as Alzheimer's disease. A galloyl dimer prorobinetinidin from Acacia mearnsii De Wild, robinetinidol-(4beta-->8)-epigallocatechin 3-O-gallate (REO), has antioxidant properties and could protect brain against acrolein-induced oxidative damage. In this study, the molecular basis of acrolein-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and the modulating effects of REO were examined. Our results indicate that REO protects SH-SY5Y cells from acrolein-induced damage by the attenuation of reactive oxygen species, the remediation of NADPH oxidase activity, the enhancement of the glutathione system, and the prevention of protein oxidation/nitration and lipid peroxidation. In order to determine the effects of REO on mitochondrial events, mitochondrial membrane potentials (Delta Psim) and caspase cascades downstream of mitochondria were assessed. REO inhibited the collapse of Delta Psi m, suggesting that REO reduces the mitochondrial dysfunction associated with acrolein treatment. REO also inhibited caspase-3 activation, which can be triggered by mitochondrial malfunctions. Furthermore, REO induced a significant reduction in the level of phospho-JNK, which is known as an apoptotic mediator in acrolein-induced neuronal cell death. Our results indicate that REO protects neurons from the deleterious effects of acrolein via the attenuation of oxidative stress, NADPH oxidase activity, GSH depletion, protein oxidation/nitration, lipid peroxidation, mitochondrial dysfunction, JNK activation, and caspase activity. These findings suggest that REO could be potentially useful as a protective agent for people exposed to acrolein.
authors.affiliation: Institute for Nanobiomedical Technology and Membrane Biology, State Key Lab of Biotherapy of Human Diseases, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. huangwen@scu.edu.cn
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.forename: Hai
authors.initials: H
authors.lastname: Niu
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Xue
authors.forename: Junxiang
authors.initials: J
authors.lastname: Li
authors.forename: Chenwei
authors.initials: C
authors.lastname: Li
mesh_terms: D000045:Acacia / Q000737:chemistry*; D000171:Acrolein; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019281:Dimerization; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; D000171:Acrolein; D002392:Catechin; C045651:epigallocatechin gallate; D019255:NADPH Oxidases; C505407:CASP3 protein, human; D053148:Caspase 3