Acetylshikonin, a novel ache inhibitor, inhibits apoptosis via upregulation of heme oxygenase-1 expression in sh-sy5y cells

Yan Wang, Wen Liang Pan, Wei Cheng Liang, Wai Kit Law, Denis Tsz-Ming Ip, Tzi Bun Ng, Mary Miu-Yee Waye, David Chi-Cheong Wan

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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 β, 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 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.

Original languageEnglish (US)
Article number937370
JournalEvidence-based Complementary and Alternative Medicine
Volume2013
DOIs
StatePublished - 2013

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