Robinetinidol-(4β→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

Article type: Research Article

Authors: Huang, Wen^{a; *} | Niu, Hai^b | Xue, Xinsheng^{a; c} | Li, Junxiang^d | Li, Chenwei^d

Affiliations: [a] 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 | [b] Mathematical College, Sichuan University, Chendu, China | [c] Intensive care unit, West China Hospital, Sichuan University, Chengdu, China | [d] School of Basic Clinical Medical, Beijing University of Traditional Chinese Medicine, Beijing, China

Correspondence: [*] Correspondence to: Wen Huang, PhD, West China Hospital/West China Medical School, Sichuan University, No.1, Keyuan 4 Lu, Gaopengdadao, Gaoxinqu, Chengdu 610041, China. Tel.: +86 028 85164076; Fax: +86 028 85164073; E-mail: huangwen@scu.edu.cn.

Abstract: Acrolein is a highly electrophilic α, β-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-(4β→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 (Δ Ψm) and caspase cascades downstream of mitochondria were assessed. REO inhibited the collapse of Δ Ψ 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.

Keywords: Flavonoids, neurodegenerative diseases, oxidative stress, reactive oxygen species

DOI: 10.3233/JAD-2010-090886

Journal: Journal of Alzheimer's Disease, vol. 21, no. 2, pp. 493-506, 2010