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

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 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.

Chrysophanol: a review of its pharmacology, toxicity and pharmacokinetics

“…identified chrysophanol as an acetylcholinesterase (AChE) inhibitor. In addition, in the H 2 O 2 ‐induced apoptosis of SH‐SY5Y and PC12 cells, chrysophanol up‐regulating haem oxygenase‐1 showed anti‐apoptotic activity . Therefore, in the future, it is necessary to further explore the neuroprotective mechanism of chrysophanol at the molecular level.…”

Silibinin, a novel chemokine receptor type 4 antagonist, inhibits chemokine ligand 12-induced migration in breast cancer cells

“…The natural product database was established as our previous described (Wang et al, 2013). For receptor preparation, the crystal structure of human CXCR4 was obtained from the Protein Data Bank (PDB 3ODU) (Wu et al, 2010).…”

“…However, little is known whether these compounds act directly as antagonist of CXCR4 receptor and its signaling pathways. In the present study, we attempted to identify ligands that bind to CXCR4 through molecular docking analysis using our in-house natural product database (Wang et al, 2013). Through this study, we have identified silibinin as potential antagonist of CXCR4 that was subsequently confirmed its antagonist activity through biochemical characterization.…”

A comparative study of Bulgarian and Turkish Asphodeline lutea root extracts: HPLC–UV profiles, enzyme inhibitory potentials and anti-proliferative activities against MCF-7 and MCF-10A cell lines

“…In addition, the anti-ulcerogenic activity of 1,8-dihydroxyanthraquinones can be attributed to their inhibitory activity on arylamine N-acetyltranseferase. There is evidence that emodin, aloe-emodin, chrysophanol, and rhein are strong acetylcholinesterase inhibitors (Wang et al, 2013), which suggests that they could be applied as alternative agents in neurodegenerative diseases (Alzheimer's disease) treatment.…”