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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 937370, 11 pages
http://dx.doi.org/10.1155/2013/937370
Research Article

Acetylshikonin, a Novel AChE Inhibitor, Inhibits Apoptosis via Upregulation of Heme Oxygenase-1 Expression in SH-SY5Y Cells

School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

Received 14 June 2013; Revised 10 September 2013; Accepted 11 September 2013

Academic Editor: Karl Wah-Keung Tsim

Copyright © 2013 Yan Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Acetylcholinesterase inhibitors are prominent alternative in current clinical treatment for AD patients. Therefore, there is a continued need to search for novel AChEIs with good clinical efficacy and less side effects. By using our in-house natural product database and AutoDock Vina as a tool in docking study, we have identified twelve phytochemicals (emodin, aloe-emodin, chrysophanol, and rhein in Rhei Radix Et Rhizoma; xanthotoxin, phellopterin, alloisoimperatorin, and imperatorin in Angelicae dahuricae Radix; shikonin, acetylshikonin, isovalerylshikonin, and , -dimethylacrylshikonin in Arnebiae Radix) as candidates of AChEIs that were not previously reported in the literature. In addition to AChEI activity, a series of cell-based experiments were conducted for the investigation of their neuroprotective activities. We found that acetylshikonin and its derivatives prevented apoptotic cell death induced by hydrogen peroxide in human and rat neuronal SH-SY5Y and PC12 cells at 10  M. We showed that acetylshikonin exhibited the most potent antiapoptosis activity through the inhibition of the generation of reactive oxygen species as well as protection of the loss of mitochondria membrane potential. Furthermore, we identified for the first time that the upregulation of heme oxygenase 1 by acetylshikonin is a key step mediating its antiapoptotic activity from oxidative stress in SH-SY5Y cells.