Acetylshikonin, a Novel AChE Inhibitor, Inhibits Apoptosis via Upregulation of Heme Oxygenase-1 Expression in SH-SY5Y Cells
Autor: | Mary M.Y. Waye, Yan Wang, Wai Kit Law, David Chi-Cheong Wan, Wei-Cheng Liang, Tzi Bun Ng, Denis Tsz-Ming Ip, Wen Liang Pan |
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Rok vydání: | 2013 |
Předmět: |
chemistry.chemical_classification
Reactive oxygen species SH-SY5Y Article Subject business.industry lcsh:Other systems of medicine Pharmacology lcsh:RZ201-999 medicine.disease_cause Neuroprotection Heme oxygenase chemistry.chemical_compound Complementary and alternative medicine chemistry Downregulation and upregulation Apoptosis Medicine Emodin business Oxidative stress Research Article |
Zdroj: | Evidence-Based Complementary and Alternative Medicine, Vol 2013 (2013) Evidence-based Complementary and Alternative Medicine : eCAM |
ISSN: | 1741-4288 1741-427X |
DOI: | 10.1155/2013/937370 |
Popis: | 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, andβ,β-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 μM. 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. |
Databáze: | OpenAIRE |
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